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Carol Aghajanian - One of the best experts on this subject based on the ideXlab platform.
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results of an abbreviated phase ii study of akt inhibitor mk 2206 in the treatment of recurrent platinum resistant high grade serous ovarian fallopian tube or Primary Peritoneal carcinoma nct 01283035
Gynecologic oncology reports, 2020Co-Authors: Elizabeth K Lee, Ursula A Matulonis, Carol Aghajanian, Zhenying Tanwasielewski, Jennifer Curtis, Robert L Coleman, Michelle S Hirsch, Lewis C Cantley, Gordon B Mills, Austin L DoyleAbstract:Platinum-resistant, recurrent, high grade epithelial ovarian carcinoma remains challenging to treat. Chemotherapy produces limited responses with modest survival benefits in the treatment of recurrent disease. In this context, targeted therapies may improve upon conventional therapies. PI3K/AKT pathway alterations are frequently found in several Cancer types, including ovarian Cancer, and thus AKT inhibition is a rational targeted therapy. Here we report the results of an abbreviated trial of AKT inhibitor MK-2206 in platinum resistant high grade serous ovarian, fallopian tube, and Primary Peritoneal Cancer with PTEN loss.
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bevacizumab shows activity in patients with low grade serous ovarian and Primary Peritoneal Cancer
International Journal of Gynecological Cancer, 2014Co-Authors: Rachel N Grisham, Qin Zhou, Alexia Iasonos, Gopa Iyer, Evis Sala, Deborah Delair, David M Hyman, Carol AghajanianAbstract:Objective Low-grade serous (LGS) ovarian and Primary Peritoneal Cancer is a rare disease with limited therapeutic options. Low response rates are observed with cytotoxic chemotherapy. However, significant responses have been reported in patients treated with bevacizumab. The objective of this study was to determine the response rate to bevacizumab with or without concurrent chemotherapy in patients with recurrent serous borderline or LGS ovarian or Primary Peritoneal Cancer. Methods This single-institution retrospective study examined the response rate to treatment with bevacizumab in patients with serous borderline or LGS Cancer. Patients were treated at the Memorial Sloan Kettering Cancer Center between 2005 and 2012. The best overall response was determined with the use of the Response Evaluation Criteria in Solid Tumors. Results A total of 17 patients were identified, 15 of whom were evaluable for the Primary end point of best overall response. Two patients were treated with bevacizumab as a single agent, and the remainder received bevacizumab in conjunction with chemotherapy (paclitaxel, topotecan, oral cyclophosphamide, gemcitabine, or gemcitabine and carboplatin). The median duration of bevacizumab administration in evaluable patients was 23 weeks (mean, 32.2 weeks; range, 6–79.4 weeks). There were no complete responses. Partial responses were observed in 6 patients (5 patients received concurrent paclitaxel, and 1 patient received concurrent gemcitabine). The overall response rate was 40%, with a response rate of 55% among the subgroup of patients with LGS Cancer. Conclusions These results indicate that bevacizumab in combination with chemotherapy is an active treatment for recurrent LGS ovarian Cancer. A prospective trial of bevacizumab in combination with paclitaxel for the treatment of LGS ovarian Cancer should be considered.
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eribulin mesylate halichondrin b analog e7389 in platinum sensitive ovarian Cancer a phase ii study ctep 7431
Journal of Clinical Oncology, 2011Co-Authors: M L Hensley, Paul Sabbatini, Carol Aghajanian, Sara Kravetz, Xiaoyu Jia, William P Tew, L Pereira, Christin Whalen, Corrine Zarwan, Suzanne BerlinAbstract:5090 Background: Eribulin mesylate is a novel tubulin inhibitor which suppresses microtubule growth without affecting depolymerization, sequestering tubulin into non-functional aggregates. In NIH:OVCAR-3 human epithelial ovarian Cancer xenograft models, eribulin increased survival and reduced size and number of metastases, with activity superior to paclitaxel. We sought to determine the frequency of objective response to treatment with eribulin in women with platinum-sensitive recurrent ovarian Cancer. Methods: Patients with recurrent, platinum-sensitive (progression-free interval from last platinum > 6 months) epithelial ovarian, fallopian tube, or Primary Peritoneal Cancer who had measurable disease, ≤ 2 prior cytotoxic regimens, ECOG performance status 0-1, and adequate organ function were eligible. Treatment: eribulin 1.4 mg/m2 over 15 minutes by vein days 1 and 8, every 21 days. Response assessed by computed tomography every other cycle. Results: 37 patients enrolled, median age 60 (range 45-77), med...
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a phase ii evaluation of bortezomib in the treatment of recurrent platinum sensitive ovarian or Primary Peritoneal Cancer a gynecologic oncology group study
Gynecologic Oncology, 2009Co-Authors: Carol Aghajanian, Russell J. Schilder, John A Blessing, Robert S Mannel, Kathleen M Darcy, Gary C Reid, Koen Degeest, Stephen C Rubin, Jacob Rotmensch, William RiordanAbstract:Abstract Objective To determine the activity and pharmacodynamics (PD) of bortezomib in platinum-sensitive epithelial ovarian or Primary Peritoneal Cancer (EOC/PPC). Patients and methods Eligible women with recurrent EOC/PPC progressing between 6 and 12 months after initial chemotherapy were treated with bortezomib on days 1, 4, 8, and 11 [1.5 (cohort I) and 1.3 (cohort II) mg/m 2 /dose]. Patients must have had initial chemotherapy only. Response Evaluation Criteria in Solid Tumors (RECIST) was assessed by computed tomography (CT) scan every 2 cycles. 20S proteasome activity was quantified in three pre-treatment and a 1-hour post-treatment (cycle one, day 1) whole blood lysates. Results Initially, 26 evaluable patients were treated at the 1.5 mg/m 2 /dose level. Objective response rate was 3.8% (1/26), a partial response. An additional 10 patients (38.5%) had stable disease. Given concerns that treatment discontinuations due to toxicity limited drug exposure/activity a second cohort of 29 evaluable patients was accrued at 1.3 mg/m 2 /dose. The 1.3 mg/m 2 /dose regimen is currently approved as an indication for multiple myeloma and mantle cell lymphoma. Treatment was more tolerable, although objective responses remained low at 6.9% (2/29, partial responses). Second stage accrual was not warranted at either dose. Bortezomib effectively inhibited 20S proteasome activity in whole blood lysates between 37 and 92% in 24/25 (96%) patients in cohort I, and 14–84% in 27/28 (96%) patients in cohort II who provided satisfactory pre- and post-treatment specimens for testing. Conclusion Bortezomib has minimal activity as a single-agent in the treatment of recurrent platinum-sensitive EOC/PPC. Treatment with bortezomib at 1.5 mg/m 2 /dose was not feasible in this patient population due to excess toxicity. Bortezomib was well tolerated at 1.3 mg/m 2 /dose.
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phase i study of abagovomab in patients with epithelial ovarian fallopian tube or Primary Peritoneal Cancer
Clinical Cancer Research, 2006Co-Authors: Paul Sabbatini, Alexia Iasonos, Carol Aghajanian, Jakob Dupont, Felicia Derosa, Elizabeth A Poynor, S Anderson, Martee L Hensley, P O Livingston, David R SpriggsAbstract:Purpose: This open-label study assessed the safety and immunogenicity of two doses and two routes of the anti-idiotypic monoclonal antibody abagovomab (formerly ACA125) in patients with epithelial ovarian, fallopian tube, or Primary Peritoneal Cancer. Experimental Design: Eligible patients from the three participating institutions were any stage at diagnosis, had relapsed, and had complete or partial response to additional chemotherapy. Patients were randomized to receive abagovomab at 2.0 versus 0.2 mg and i.m. versus s.c. for four immunizations every 2 weeks and then monthly for two additional immunizations. Planned evaluation included interval physical examinations and laboratory assessments with immune assessment, including HLA typing, human anti-mouse antibody, ELISA, and enzyme-linked immunospot. Patients were required to remain on study until week 10 (the first post-baseline Ab3 determination) to be considered for immunologic assessment. The Primary end points were safety and immunogenicity primarily determined by Ab3 response. Results: Forty-two patients received at least one vaccination and were eligible for safety analysis. Thirty-three patients were available for Ab3 analysis (removed for progression of disease, 6; withdrawal of consent, 2; unrelated adverse event, 1). The most common adverse events were self-limited pain at injection site, myalgia, and fever. No hematologic or nonhematologic toxicity grade >2 related to immunization was seen. Ab3 was detectable in all patients (median, 236,794 ng/mL); none of route of administration ( P = 0.6268), dose ( P = 0.4602), or cohort ( P = 0.4944) was statistically significant in terms of effect on maximum post-baseline Ab3 titer. Human anti-mouse antibody was not detectable at baseline but was present in all patients at week 16 (range, 488-45,000 ng/mL). Conclusions: Immunization with abagovomab is well tolerated and induced robust Ab3 responses at the two doses and routes tested. A phase III randomized study with abagovomab (2.0 mg s.c.) is warranted.
Russell J. Schilder - One of the best experts on this subject based on the ideXlab platform.
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abstract ct151 a phase ii study of nlg207 formerly crlx101 in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian fallopian tube or Primary Peritoneal Cancer
Cancer Research, 2019Co-Authors: Linda R Duska, Russell J. Schilder, C N Krasner, Kathleen N Moore, David M Omalley, Cara Mathews, Premal H Thaker, Austin Miller, Christopher Purdy, A J LeycoAbstract:Background: NLG207 (formerly CRLX101) is an investigational nanoparticle-drug conjugate (NDC) composed of a cyclodextrin-based polymer backbone linked to camptothecin, a topoisomerase-1 inhibitor. NDCs enhance drug delivery to tumors where gradual payload release inside Cancer cells augments antitumor activity while reducing toxicity. The RP2D of CRLX101 was previously set at 15 mg/m2 Q2W in combination with 80 mg/m2 weekly paclitaxel in Phase I and reported at ESMO 2016. This abstract will include data from both the Phase Ib and the phase II expansion. Methods: In this Phase II single arm study, patients were treated with NLG207 (Q2W) and 80 mg/m2 paclitaxel (3 wks on/1 wk off) repeated q 28 days until progression or toxicity. Primary objective was overall response (CR + PR) via RECIST v1.1 in women with recurrent platinum resistant epithelial ovarian, fallopian tube or Primary Peritoneal Cancer. Progression free survival (PFS), duration of response (DOR), and safety were also assessed. Results: Thirty patients were enrolled and all completed at least one cycle. Median age was 62 (44-76) years. 57% of patients received ≥3 prior therapies. There were 8/30 confirmed responses for an overall response rate (ORR) of 26.7% (95% CI 14.2%, 44.4%), including one complete response (CR). ORR for platinum resistant patients (n=17) was 23.5% (4/17) vs. 30.8% (4/13) for those who were platinum sensitive (n=13) to their most recent platinum regimen. Best response (including unconfirmed) for platinum resistant patients was 41.2% (7/17) including 7 PRs. Five additional platinum resistant patients achieved stable disease (SD). Median PFS (mPFS) for all study patients was 5.4 months. The mPFS was similar for both platinum resistant at 5.5 months and platinum sensitive at 5.4 months. Median DOR was 7.2 months for platinum resistant patients vs. 4.7 months for the platinum sensitive group. The most common grade 3/4 adverse events (AEs) attributed to study treatment were: decreased neutrophil count (13 patients, 43%), anemia (3 patients, 10%), hematuria (2 patients, 7%); urinary tract infection (UTI), cystitis, hypertension, and hypokalemia (all seen in 1 patient, 3%). PK data will be included in the full presentation. Conclusions: NLG207 is a potentially best-in-class topoisomerase 1 inhibitor with demonstrated antitumor activity in recurrent ovarian Cancer including those who have become resistant to platinum therapy. AE profile of this combination is consistent with that seen for paclitaxel as a single agent except for cystitis, hematuria and UTI. It was well-tolerated in combination with weekly paclitaxel in heavily pre-treated patients. NLG207 warrants further investigation in combination therapy regimens for recurrent ovarian, fallopian tube or Primary Peritoneal Cancer, particularly in platinum resistant patients. Citation Format: Linda Duska, David M. O9Malley, Carolyn Krasner, Russell J. Schilder, Cara Mathews, Kathleen Moore, Premal Thaker, Austin Miller, Christopher Purdy, A.J. Leyco, Christopher Smith, Deborah Mercier, Lucinda Tennant, Eugene Kennedy, Nicholas Vahanian, Charles Link. A Phase II study of NLG207 (formerly CRLX101) in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian, fallopian tube or Primary Peritoneal Cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT151.
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A phase II evaluation of AMG 102 (rilotumumab) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or Primary Peritoneal carcinoma: a Gynecologic Oncology Group study.
Gynecologic oncology, 2013Co-Authors: Lainie P. Martin, Michael W. Sill, Mark S. Shahin, Matthew A. Powell, Paul Disilvestro, Lisa M. Landrum, Stephanie Gaillard, Michael J. Goodheart, James S. Hoffman, Russell J. SchilderAbstract:Abstract Objective This open-label, multi-institutional phase II trial evaluated activity and safety of rilotumumab (AMG 102), a monoclonal antibody that targets HGF (hepatocyte growth factor), the ligand for the MET receptor, in women with recurrent or persistent epithelial ovarian, fallopian tube or Primary Peritoneal Cancer. Patients and methods Women were eligible for treatment with rilotumumab if they had measurable disease, a performance status of 0, 1 or 2, previously received platinum-based therapy with a progression-free interval of Results Thirty-one women enrolled and received rilotumumab. All were eligible for analysis. One patient achieved a complete response (3.2%; 90% CI 0.2–14%), and two women had 6-month PFS (6.5%; 90% CI 1.1–19%). Most adverse events were grade 1 or 2, with no grade 4 adverse events. Grade 3 adverse events were gastrointestinal (4), metabolic (3) anemia (3), a thromboembolic event (1), ventricular tachycardia (1), hypotension during infusion (1) and fatigue (1). The study was stopped after the first stage of accrual. Conclusion Rilotumumab was well-tolerated, but had limited activity. The level of activity does not warrant further evaluation of rilotumumab as a single agent in patients with ovarian Cancer.
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a phase ii evaluation of bortezomib in the treatment of recurrent platinum sensitive ovarian or Primary Peritoneal Cancer a gynecologic oncology group study
Gynecologic Oncology, 2009Co-Authors: Carol Aghajanian, Russell J. Schilder, John A Blessing, Robert S Mannel, Kathleen M Darcy, Gary C Reid, Koen Degeest, Stephen C Rubin, Jacob Rotmensch, William RiordanAbstract:Abstract Objective To determine the activity and pharmacodynamics (PD) of bortezomib in platinum-sensitive epithelial ovarian or Primary Peritoneal Cancer (EOC/PPC). Patients and methods Eligible women with recurrent EOC/PPC progressing between 6 and 12 months after initial chemotherapy were treated with bortezomib on days 1, 4, 8, and 11 [1.5 (cohort I) and 1.3 (cohort II) mg/m 2 /dose]. Patients must have had initial chemotherapy only. Response Evaluation Criteria in Solid Tumors (RECIST) was assessed by computed tomography (CT) scan every 2 cycles. 20S proteasome activity was quantified in three pre-treatment and a 1-hour post-treatment (cycle one, day 1) whole blood lysates. Results Initially, 26 evaluable patients were treated at the 1.5 mg/m 2 /dose level. Objective response rate was 3.8% (1/26), a partial response. An additional 10 patients (38.5%) had stable disease. Given concerns that treatment discontinuations due to toxicity limited drug exposure/activity a second cohort of 29 evaluable patients was accrued at 1.3 mg/m 2 /dose. The 1.3 mg/m 2 /dose regimen is currently approved as an indication for multiple myeloma and mantle cell lymphoma. Treatment was more tolerable, although objective responses remained low at 6.9% (2/29, partial responses). Second stage accrual was not warranted at either dose. Bortezomib effectively inhibited 20S proteasome activity in whole blood lysates between 37 and 92% in 24/25 (96%) patients in cohort I, and 14–84% in 27/28 (96%) patients in cohort II who provided satisfactory pre- and post-treatment specimens for testing. Conclusion Bortezomib has minimal activity as a single-agent in the treatment of recurrent platinum-sensitive EOC/PPC. Treatment with bortezomib at 1.5 mg/m 2 /dose was not feasible in this patient population due to excess toxicity. Bortezomib was well tolerated at 1.3 mg/m 2 /dose.
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phase ii study comparing volociximab an antiangiogenic antibody and pegylated liposomal doxorubicin pld with pld alone in recurrent ovarian or Primary Peritoneal Cancer
Journal of Clinical Oncology, 2009Co-Authors: I Vergote, Nicoletta Colombo, Ernst Lengyel, Elzbieta Kutarska, J M Del Campo, C H Pippitt, Antonio Casado, K Gilder, Russell J. SchilderAbstract:5560 Background: Volociximab (V), a chimeric monoclonal antibody with direct antitumor effects, blocks α5β1 binding to fibronectin and induces apoptosis in proliferating endothelial cells. A Phase I/II study was performed to evaluate PLD with/without V in patients (pts) with recurrent ovarian or Primary Peritoneal Cancer that relapsed after platinum/taxane-based chemotherapy (maximum 2 prior lines). Methods: A 3-arm adaptive randomization design compared efficacy and safety of PLD (40 mg/m2 q4wk) + V (15 mg/kg q2wk or qwk) vs. PLD alone. Pts were stratified by platinum sensitivity and received treatment until disease progression or unacceptable toxicity. The Primary endpoint was progression-free survival (PFS). Pharmacokinetic (PK) and pharmacodynamic effects were also evaluated. Results: There were 6 iterations of adaptive randomization based on accumulating PFS data. 127 pts were randomized: 66 in Group A (PLD), 34 in Group B (PLD+V [q2wk]), and 27 in Group C (PLD+V [qwk]). The incidence of AEs was bala...
Michael W. Sill - One of the best experts on this subject based on the ideXlab platform.
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A phase II evaluation of AMG 102 (rilotumumab) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or Primary Peritoneal carcinoma: a Gynecologic Oncology Group study.
Gynecologic oncology, 2013Co-Authors: Lainie P. Martin, Michael W. Sill, Mark S. Shahin, Matthew A. Powell, Paul Disilvestro, Lisa M. Landrum, Stephanie Gaillard, Michael J. Goodheart, James S. Hoffman, Russell J. SchilderAbstract:Abstract Objective This open-label, multi-institutional phase II trial evaluated activity and safety of rilotumumab (AMG 102), a monoclonal antibody that targets HGF (hepatocyte growth factor), the ligand for the MET receptor, in women with recurrent or persistent epithelial ovarian, fallopian tube or Primary Peritoneal Cancer. Patients and methods Women were eligible for treatment with rilotumumab if they had measurable disease, a performance status of 0, 1 or 2, previously received platinum-based therapy with a progression-free interval of Results Thirty-one women enrolled and received rilotumumab. All were eligible for analysis. One patient achieved a complete response (3.2%; 90% CI 0.2–14%), and two women had 6-month PFS (6.5%; 90% CI 1.1–19%). Most adverse events were grade 1 or 2, with no grade 4 adverse events. Grade 3 adverse events were gastrointestinal (4), metabolic (3) anemia (3), a thromboembolic event (1), ventricular tachycardia (1), hypotension during infusion (1) and fatigue (1). The study was stopped after the first stage of accrual. Conclusion Rilotumumab was well-tolerated, but had limited activity. The level of activity does not warrant further evaluation of rilotumumab as a single agent in patients with ovarian Cancer.
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a phase ii study of two topotecan regimens evaluated in recurrent platinum sensitive ovarian fallopian tube or Primary Peritoneal Cancer a gynecologic oncology group study gog 146q
Gynecologic Oncology, 2011Co-Authors: Thomas J Herzog, Michael W. Sill, Mark S. Shahin, David M Omalley, Joan L Walker, Koen Degeest, David G Mutch, Sheldon A Weiner, Robert L DebernardoAbstract:Abstract Objective. To evaluate the efficacy and safety of topotecan in patients with recurrent ovarian, Primary Peritoneal, and fallopian tube carcinomas. Methods. A randomized phase II analysis of platinum-sensitive patients with measurable disease was performed independently assessing intravenous topotecan 1.25mg/m 2 daily × 5 every 21days (regimen I) and topotecan 4.0mg/m 2 /day on days 1, 8, and 15 of a 28-day cycle (regimen II). All patients were treated until disease progression, unmanageable toxicity, or patient refusal. Insufficient accrual related to regimen I resulted in a redesign of the study as a single arm phase II trial assessing only regimen II. More complete efficacy data is presented for regimen II as enrollment on regimen I was insufficient for some analyses. Results. A total of 81 patients were enrolled. One patient was ineligible. Fifteen patients received regimen I, while 65 patients were treated with regimen II. The response rate on regimen I (daily × 5) was 27% (90% CI: 10–51%) and 12% (90% CI: 6–21%) on regimen II (weekly). The median PFS and OS were 4.8 and 27.8months, respectively, for regimen II. Grade 3/4 neutropenia rate was 93% with daily × 5 dosing and 28% for weekly treatment. Febrile neutropenia was very low in both groups. Conclusion. The weekly regimen of topotecan appeared less active but resulted in less toxicity than the daily regimen in platinum-sensitive recurrent ovarian Cancer patients.
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phase ii trial of bevacizumab in persistent or recurrent epithelial ovarian Cancer or Primary Peritoneal Cancer a gynecologic oncology group study
Journal of Clinical Oncology, 2007Co-Authors: Robert A Burger, Michael W. Sill, Bradley J Monk, Benjamin E Greer, Joel I SoroskyAbstract:Purpose Vascular endothelial growth factor (VEGF) seems to be a promoter of tumor progression for epithelial ovarian Cancer (EOC) and Primary Peritoneal Cancer (PPC). We conducted a phase II trial to assess the efficacy and tolerability of single-agent bevacizumab, an anti-VEGF monoclonal antibody. Patients and Methods Eligible patients had persistent or recurrent EOC/PPC after one to two prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group performance status of at least 2. Treatment consisted of bevacizumab 15 mg/kg intravenously every 21 days until disease progression or prohibitive toxicity. Primary end points were progression-free survival (PFS) at 6 months and clinical response. Results The study consisted of 62 eligible and assessable patients, median age 57 years, 41 (66.1%) having received two prior regimens and 36 (58.1%) considered platinum resistant. Grade 3 adverse events at least possibly related to bevacizumab were hematologic (1), GI (3), hypertension (6), thromboemb...
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phase ii trial of bevacizumab in persistent or recurrent epithelial ovarian Cancer or Primary Peritoneal Cancer a gynecologic oncology group study
Journal of Clinical Oncology, 2007Co-Authors: Robert A Burger, Michael W. Sill, Bradley J Monk, Benjamin E Greer, Joel I SoroskyAbstract:PURPOSE: Vascular endothelial growth factor (VEGF) seems to be a promoter of tumor progression for epithelial ovarian Cancer (EOC) and Primary Peritoneal Cancer (PPC). We conducted a phase II trial to assess the efficacy and tolerability of single-agent bevacizumab, an anti-VEGF monoclonal antibody. PATIENTS AND METHODS: Eligible patients had persistent or recurrent EOC/PPC after one to two prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group performance status of at least 2. Treatment consisted of bevacizumab 15 mg/kg intravenously every 21 days until disease progression or prohibitive toxicity. Primary end points were progression-free survival (PFS) at 6 months and clinical response. RESULTS: The study consisted of 62 eligible and assessable patients, median age 57 years, 41 (66.1%) having received two prior regimens and 36 (58.1%) [CORRECTED] considered platinum resistant. Grade 3 adverse events at least possibly related to bevacizumab were hematologic (1), GI (3), hypertension (6), thromboembolism (1), allergy (2), hepatic (1), pain (3), coagulation (1), constitutional (1), and dyspnea (1). Grade 4 adverse events included pulmonary embolus (1), vomiting and constipation (1), and proteinuria (1). Thirteen patients (21.0%) experienced clinical responses (two complete, 11 partial; median response duration, 10 months), and 25 (40.3%) survived progression free for at least 6 months. Median PFS and overall survival were 4.7 and 17 months, respectively. There was no significant association of prior platinum sensitivity, age, number of prior chemotherapeutic regimens, or performance status with the hazard of progression or death. CONCLUSION: Bevacizumab seems to be well tolerated and active in the second- and third-line treatment of patients with EOC/PPC and merits phase III investigation.
Kathleen N Moore - One of the best experts on this subject based on the ideXlab platform.
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a phase ib ii and pharmacokinetic study of ep0057 formerly crlx101 in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian fallopian tube or Primary Peritoneal Cancer
Gynecologic Oncology, 2021Co-Authors: Linda R Duska, C N Krasner, Kathleen N Moore, David M Omalley, Cara Mathews, Premal H Thaker, John L Hays, Susan C Modesitt, Anthony B Miller, Christopher PurdyAbstract:Abstract Background: EP0057 (formerly CRLX101) is an investigational nanoparticle-drug conjugate (NDC) of a cyclodextrin-based polymer backbone plus camptothecin, a topoisomerase-1 inhibitor. Prior studies showed efficacy in recurrent or persistent, epithelial ovarian, fallopian tube or Primary Peritoneal Cancer (EOC). Methods: This phase Ib/2 trial assessed safety and efficacy of EP0057 Q2W plus weekly paclitaxel in patients with EOC. The recommended phase 2 dose (RP2D) was identified using a 3+3 design. The single-arm phase 2 assessed overall response (ORR) per RECIST 1.1 in patients previously treated with bevacizumab. Secondary objectives included progression free survival (PFS) and duration of response. Results: The RP2D was established as 15 mg/m2 EP0057 Q2W plus 80 mg/m2 paclitaxel administered 3 weeks on/1 week off. Nine patients enrolled on phase 1b, with no DLTs; 21 additional patients enrolled on phase 2. All completed > 1 cycle. Median age was 62 (44-76) years, 57% ≥3 prior therapies. For the Primary analysis, 6/19 patients with prior bevacizumab had confirmed responses (ORR=31.6% (95% CI: 15.4% to 54.0%)) including one complete response (CR). Median PFS was 5.4 months. Most common grade 3/4 adverse events attributed to treatment were decreased neutrophil count (13, 43%) and anemia (3, 10%). Conclusions: Although the observed ORR was not statistically better than the historical control rate, EP0057 remains an interesting option for treatment of recurrent EOC. EP0057 exhibits high plasma drug retention, slow clearance, and controlled slow release of CPT from the polymer when administered alone and with paclitaxel. (NCT02389985) 242 words
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parp inhibitors in the management of ovarian Cancer asco guideline
Journal of Clinical Oncology, 2020Co-Authors: Christina Lacchetti, Kathleen N Moore, Carolyn Y Muller, Susana Banerjee, Annie Ellis, Kathleen Maxian, Michael A Bookman, Monica Brown Jones, Stephanie Lheureux, Patricia RodriguezAbstract:PURPOSETo provide recommendations on the use of poly(ADP-ribose) polymerase inhibitors (PARPis) for management of epithelial ovarian, tubal, or Primary Peritoneal Cancer (EOC).METHODSRandomized, co...
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abstract ct151 a phase ii study of nlg207 formerly crlx101 in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian fallopian tube or Primary Peritoneal Cancer
Cancer Research, 2019Co-Authors: Linda R Duska, Russell J. Schilder, C N Krasner, Kathleen N Moore, David M Omalley, Cara Mathews, Premal H Thaker, Austin Miller, Christopher Purdy, A J LeycoAbstract:Background: NLG207 (formerly CRLX101) is an investigational nanoparticle-drug conjugate (NDC) composed of a cyclodextrin-based polymer backbone linked to camptothecin, a topoisomerase-1 inhibitor. NDCs enhance drug delivery to tumors where gradual payload release inside Cancer cells augments antitumor activity while reducing toxicity. The RP2D of CRLX101 was previously set at 15 mg/m2 Q2W in combination with 80 mg/m2 weekly paclitaxel in Phase I and reported at ESMO 2016. This abstract will include data from both the Phase Ib and the phase II expansion. Methods: In this Phase II single arm study, patients were treated with NLG207 (Q2W) and 80 mg/m2 paclitaxel (3 wks on/1 wk off) repeated q 28 days until progression or toxicity. Primary objective was overall response (CR + PR) via RECIST v1.1 in women with recurrent platinum resistant epithelial ovarian, fallopian tube or Primary Peritoneal Cancer. Progression free survival (PFS), duration of response (DOR), and safety were also assessed. Results: Thirty patients were enrolled and all completed at least one cycle. Median age was 62 (44-76) years. 57% of patients received ≥3 prior therapies. There were 8/30 confirmed responses for an overall response rate (ORR) of 26.7% (95% CI 14.2%, 44.4%), including one complete response (CR). ORR for platinum resistant patients (n=17) was 23.5% (4/17) vs. 30.8% (4/13) for those who were platinum sensitive (n=13) to their most recent platinum regimen. Best response (including unconfirmed) for platinum resistant patients was 41.2% (7/17) including 7 PRs. Five additional platinum resistant patients achieved stable disease (SD). Median PFS (mPFS) for all study patients was 5.4 months. The mPFS was similar for both platinum resistant at 5.5 months and platinum sensitive at 5.4 months. Median DOR was 7.2 months for platinum resistant patients vs. 4.7 months for the platinum sensitive group. The most common grade 3/4 adverse events (AEs) attributed to study treatment were: decreased neutrophil count (13 patients, 43%), anemia (3 patients, 10%), hematuria (2 patients, 7%); urinary tract infection (UTI), cystitis, hypertension, and hypokalemia (all seen in 1 patient, 3%). PK data will be included in the full presentation. Conclusions: NLG207 is a potentially best-in-class topoisomerase 1 inhibitor with demonstrated antitumor activity in recurrent ovarian Cancer including those who have become resistant to platinum therapy. AE profile of this combination is consistent with that seen for paclitaxel as a single agent except for cystitis, hematuria and UTI. It was well-tolerated in combination with weekly paclitaxel in heavily pre-treated patients. NLG207 warrants further investigation in combination therapy regimens for recurrent ovarian, fallopian tube or Primary Peritoneal Cancer, particularly in platinum resistant patients. Citation Format: Linda Duska, David M. O9Malley, Carolyn Krasner, Russell J. Schilder, Cara Mathews, Kathleen Moore, Premal Thaker, Austin Miller, Christopher Purdy, A.J. Leyco, Christopher Smith, Deborah Mercier, Lucinda Tennant, Eugene Kennedy, Nicholas Vahanian, Charles Link. A Phase II study of NLG207 (formerly CRLX101) in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian, fallopian tube or Primary Peritoneal Cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT151.
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phase ib study of anti mesothelin antibody drug conjugate anetumab ravtansine in combination with pegylated liposomal doxorubicin in platinum resistant ovarian fallopian tube or Primary Peritoneal Cancer
Journal of Clinical Oncology, 2018Co-Authors: Iurie Bulat, Kathleen N Moore, Alexei Haceatrean, John Chung, Prabhu Rajagopalan, Chenghua Xia, Dirk Laurent, Barrett H Childs, Alessandro D SantinAbstract:5571Background: Anetumab ravtansine (AR) comprises a novel fully human anti-mesothelin IgG1 antibody conjugated to the maytansinoid tubulin inhibitor DM4. A phase Ib dose escalation was conducted i...
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safety and activity of mirvetuximab soravtansine imgn853 a folate receptor alpha targeting antibody drug conjugate in platinum resistant ovarian fallopian tube or Primary Peritoneal Cancer a phase i expansion study
Journal of Clinical Oncology, 2017Co-Authors: Kathleen N Moore, Lainie P. Martin, David M Omalley, Ursula A Matulonis, Jason A Konner, Raymond P Perez, Todd Michael Bauer, Rodrigo Ruizsoto, Michael J BirrerAbstract:PurposeThis phase I expansion cohort study evaluated the safety and clinical activity of mirvetuximab soravtansine (IMGN853), an antibody–drug conjugate consisting of a humanized anti–folate receptor alpha (FRα) monoclonal antibody linked to the tubulin-disrupting maytansinoid DM4, in a population of patients with FRα-positive and platinum-resistant ovarian Cancer.Patients and MethodsPatients with platinum-resistant epithelial ovarian, fallopian tube, or Primary Peritoneal Cancer received IMGN853 at 6.0 mg/kg (adjusted ideal body weight) once every 3 weeks. Eligibility included a minimum requirement of FRα positivity by immunohistochemistry (≥ 25% of tumor cells with at least 2+ staining intensity). Adverse events, tumor response (via Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), and progression-free survival (PFS) were determined.ResultsForty-six patients were enrolled. Adverse events were generally mild (≤ grade 2), with diarrhea (44%), blurred vision (41%), nausea (37%), and fatig...
David M Omalley - One of the best experts on this subject based on the ideXlab platform.
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a phase ib ii and pharmacokinetic study of ep0057 formerly crlx101 in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian fallopian tube or Primary Peritoneal Cancer
Gynecologic Oncology, 2021Co-Authors: Linda R Duska, C N Krasner, Kathleen N Moore, David M Omalley, Cara Mathews, Premal H Thaker, John L Hays, Susan C Modesitt, Anthony B Miller, Christopher PurdyAbstract:Abstract Background: EP0057 (formerly CRLX101) is an investigational nanoparticle-drug conjugate (NDC) of a cyclodextrin-based polymer backbone plus camptothecin, a topoisomerase-1 inhibitor. Prior studies showed efficacy in recurrent or persistent, epithelial ovarian, fallopian tube or Primary Peritoneal Cancer (EOC). Methods: This phase Ib/2 trial assessed safety and efficacy of EP0057 Q2W plus weekly paclitaxel in patients with EOC. The recommended phase 2 dose (RP2D) was identified using a 3+3 design. The single-arm phase 2 assessed overall response (ORR) per RECIST 1.1 in patients previously treated with bevacizumab. Secondary objectives included progression free survival (PFS) and duration of response. Results: The RP2D was established as 15 mg/m2 EP0057 Q2W plus 80 mg/m2 paclitaxel administered 3 weeks on/1 week off. Nine patients enrolled on phase 1b, with no DLTs; 21 additional patients enrolled on phase 2. All completed > 1 cycle. Median age was 62 (44-76) years, 57% ≥3 prior therapies. For the Primary analysis, 6/19 patients with prior bevacizumab had confirmed responses (ORR=31.6% (95% CI: 15.4% to 54.0%)) including one complete response (CR). Median PFS was 5.4 months. Most common grade 3/4 adverse events attributed to treatment were decreased neutrophil count (13, 43%) and anemia (3, 10%). Conclusions: Although the observed ORR was not statistically better than the historical control rate, EP0057 remains an interesting option for treatment of recurrent EOC. EP0057 exhibits high plasma drug retention, slow clearance, and controlled slow release of CPT from the polymer when administered alone and with paclitaxel. (NCT02389985) 242 words
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abstract ct151 a phase ii study of nlg207 formerly crlx101 in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian fallopian tube or Primary Peritoneal Cancer
Cancer Research, 2019Co-Authors: Linda R Duska, Russell J. Schilder, C N Krasner, Kathleen N Moore, David M Omalley, Cara Mathews, Premal H Thaker, Austin Miller, Christopher Purdy, A J LeycoAbstract:Background: NLG207 (formerly CRLX101) is an investigational nanoparticle-drug conjugate (NDC) composed of a cyclodextrin-based polymer backbone linked to camptothecin, a topoisomerase-1 inhibitor. NDCs enhance drug delivery to tumors where gradual payload release inside Cancer cells augments antitumor activity while reducing toxicity. The RP2D of CRLX101 was previously set at 15 mg/m2 Q2W in combination with 80 mg/m2 weekly paclitaxel in Phase I and reported at ESMO 2016. This abstract will include data from both the Phase Ib and the phase II expansion. Methods: In this Phase II single arm study, patients were treated with NLG207 (Q2W) and 80 mg/m2 paclitaxel (3 wks on/1 wk off) repeated q 28 days until progression or toxicity. Primary objective was overall response (CR + PR) via RECIST v1.1 in women with recurrent platinum resistant epithelial ovarian, fallopian tube or Primary Peritoneal Cancer. Progression free survival (PFS), duration of response (DOR), and safety were also assessed. Results: Thirty patients were enrolled and all completed at least one cycle. Median age was 62 (44-76) years. 57% of patients received ≥3 prior therapies. There were 8/30 confirmed responses for an overall response rate (ORR) of 26.7% (95% CI 14.2%, 44.4%), including one complete response (CR). ORR for platinum resistant patients (n=17) was 23.5% (4/17) vs. 30.8% (4/13) for those who were platinum sensitive (n=13) to their most recent platinum regimen. Best response (including unconfirmed) for platinum resistant patients was 41.2% (7/17) including 7 PRs. Five additional platinum resistant patients achieved stable disease (SD). Median PFS (mPFS) for all study patients was 5.4 months. The mPFS was similar for both platinum resistant at 5.5 months and platinum sensitive at 5.4 months. Median DOR was 7.2 months for platinum resistant patients vs. 4.7 months for the platinum sensitive group. The most common grade 3/4 adverse events (AEs) attributed to study treatment were: decreased neutrophil count (13 patients, 43%), anemia (3 patients, 10%), hematuria (2 patients, 7%); urinary tract infection (UTI), cystitis, hypertension, and hypokalemia (all seen in 1 patient, 3%). PK data will be included in the full presentation. Conclusions: NLG207 is a potentially best-in-class topoisomerase 1 inhibitor with demonstrated antitumor activity in recurrent ovarian Cancer including those who have become resistant to platinum therapy. AE profile of this combination is consistent with that seen for paclitaxel as a single agent except for cystitis, hematuria and UTI. It was well-tolerated in combination with weekly paclitaxel in heavily pre-treated patients. NLG207 warrants further investigation in combination therapy regimens for recurrent ovarian, fallopian tube or Primary Peritoneal Cancer, particularly in platinum resistant patients. Citation Format: Linda Duska, David M. O9Malley, Carolyn Krasner, Russell J. Schilder, Cara Mathews, Kathleen Moore, Premal Thaker, Austin Miller, Christopher Purdy, A.J. Leyco, Christopher Smith, Deborah Mercier, Lucinda Tennant, Eugene Kennedy, Nicholas Vahanian, Charles Link. A Phase II study of NLG207 (formerly CRLX101) in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian, fallopian tube or Primary Peritoneal Cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT151.
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safety and activity of mirvetuximab soravtansine imgn853 a folate receptor alpha targeting antibody drug conjugate in platinum resistant ovarian fallopian tube or Primary Peritoneal Cancer a phase i expansion study
Journal of Clinical Oncology, 2017Co-Authors: Kathleen N Moore, Lainie P. Martin, David M Omalley, Ursula A Matulonis, Jason A Konner, Raymond P Perez, Todd Michael Bauer, Rodrigo Ruizsoto, Michael J BirrerAbstract:PurposeThis phase I expansion cohort study evaluated the safety and clinical activity of mirvetuximab soravtansine (IMGN853), an antibody–drug conjugate consisting of a humanized anti–folate receptor alpha (FRα) monoclonal antibody linked to the tubulin-disrupting maytansinoid DM4, in a population of patients with FRα-positive and platinum-resistant ovarian Cancer.Patients and MethodsPatients with platinum-resistant epithelial ovarian, fallopian tube, or Primary Peritoneal Cancer received IMGN853 at 6.0 mg/kg (adjusted ideal body weight) once every 3 weeks. Eligibility included a minimum requirement of FRα positivity by immunohistochemistry (≥ 25% of tumor cells with at least 2+ staining intensity). Adverse events, tumor response (via Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), and progression-free survival (PFS) were determined.ResultsForty-six patients were enrolled. Adverse events were generally mild (≤ grade 2), with diarrhea (44%), blurred vision (41%), nausea (37%), and fatig...
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a phase ii study of two topotecan regimens evaluated in recurrent platinum sensitive ovarian fallopian tube or Primary Peritoneal Cancer a gynecologic oncology group study gog 146q
Gynecologic Oncology, 2011Co-Authors: Thomas J Herzog, Michael W. Sill, Mark S. Shahin, David M Omalley, Joan L Walker, Koen Degeest, David G Mutch, Sheldon A Weiner, Robert L DebernardoAbstract:Abstract Objective. To evaluate the efficacy and safety of topotecan in patients with recurrent ovarian, Primary Peritoneal, and fallopian tube carcinomas. Methods. A randomized phase II analysis of platinum-sensitive patients with measurable disease was performed independently assessing intravenous topotecan 1.25mg/m 2 daily × 5 every 21days (regimen I) and topotecan 4.0mg/m 2 /day on days 1, 8, and 15 of a 28-day cycle (regimen II). All patients were treated until disease progression, unmanageable toxicity, or patient refusal. Insufficient accrual related to regimen I resulted in a redesign of the study as a single arm phase II trial assessing only regimen II. More complete efficacy data is presented for regimen II as enrollment on regimen I was insufficient for some analyses. Results. A total of 81 patients were enrolled. One patient was ineligible. Fifteen patients received regimen I, while 65 patients were treated with regimen II. The response rate on regimen I (daily × 5) was 27% (90% CI: 10–51%) and 12% (90% CI: 6–21%) on regimen II (weekly). The median PFS and OS were 4.8 and 27.8months, respectively, for regimen II. Grade 3/4 neutropenia rate was 93% with daily × 5 dosing and 28% for weekly treatment. Febrile neutropenia was very low in both groups. Conclusion. The weekly regimen of topotecan appeared less active but resulted in less toxicity than the daily regimen in platinum-sensitive recurrent ovarian Cancer patients.
