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I Vergote - One of the best experts on this subject based on the ideXlab platform.

  • 403 phase 3 trial of tumor treating fields concomitant with weekly paclitaxel for platinum resistant Ovarian Cancer engot ov50 gog 329 innovate 3
    International Journal of Gynecologic Cancer, 2020
    Co-Authors: I Vergote, Robert L Coleman, Jalid Sehouli, R Fossati, Bradley J Monk, Larry J Copeland, David M Omalley
    Abstract:

    Introduction/Background Tumor Treating Fields (TTFields) are a non-invasive, antimitotic Cancer therapy. The Phase 2 INNOVATE study demonstrated safety of TTFields/weekly paclitaxel in 31 PROC (Platinum-Resistant Ovarian Cancer) patients (Vergote Gyn Onc 2018); efficacy: median PFS 8.9 months, 25% partial response,71% clinical benefit and 61% 1-year survival rate. This phase 3 ENGOT-ov50/GOG-329/INNOVATE-3 study [NCT03940196] investigates TTFields plus weekly paclitaxel in PROC patients. Methodology Patients (N=540) will have PROC (RECIST V1.1) within 6 months of last platinum therapy with maximum of 2–5 prior lines of systemic therapy, ECOG 0–1 and no peripheral neuropathy >grade1. Patients with primary refractory disease will be excluded. Patients will be randomized 1:1 to weekly paclitaxel alone or weekly paclitaxel (starting of dose 80 mg/m2 weekly for 8 weeks, and then on Days 1, 8, and 15 for subsequent 28-day cycle ) plus TTFields (200 kHz for 18 hours/day and continued if no progression in the abdominal or pelvic regions (‘in-field region’) per RECIST V1.1. Clinical follow-up will be performed q4w, with radiological follow-up (CT or MRI scans of the abdomen and chest) q8w. The primary endpoint is overall survival. Secondary endpoints: PFS, objective response rate, AEs, and quality of life (EORTC QLQ-C30 with QLQ-OV28). Sample size (n=540) will detect an increase in median OS from 12 to 16 months (HR 0.75). Data Monitoring Committee (DMC) meeting (March 2020) concluded that data to-date showed no safety issues and recommended trial continuation. Results TiP N/A Conclusion TiP N/A Disclosures

  • 358 phase 3 trial of tumor treating fields concomitant with weekly paclitaxel for platinum resistant Ovarian Cancer engot ov50 gog 329 innovate 3
    The Poster, 2020
    Co-Authors: I Vergote, Vanda Salutari, David Cibula, Jacob Korach, Eleftherios P Samartzis, Jalid Sehouli, R Fossati, Antonio Gonzalez Martin, I Tsibulak, Brian M Slomovitz
    Abstract:

    Background Tumor Treating Fields (TTFields) are a non-invasive, antimitotic Cancer therapy. The Phase 2 INNOVATE study demonstrated safety of TTFields/weekly paclitaxel in 31 PROC (Platinum-Resistant Ovarian Cancer) patients (Vergote Gyn Onc 2018); efficacy: median PFS 8.9 months, 25% partial response,71% clinical benefit and 61% 1-year survival rate. This phase 3 ENGOT-ov50/GOG-329/INNOVATE-3 study [NCT03940196] investigates TTFields plus weekly paclitaxel in PROC patients. Study Design Patients (N=540) will have PROC (RECIST V1.1) within 6 months of last platinum therapy with maximum of 2–5 prior lines of systemic therapy, ECOG 0–1 and no peripheral neuropathy >grade1. Patients with primary refractory disease will be excluded. Patients will be randomized 1:1 to weekly paclitaxel alone or weekly paclitaxel (starting of dose 80 mg/m2 weekly for 8 weeks, and then on Days 1, 8, and 15 for subsequent 28-day cycle ) plus TTFields (200 kHz for 18 hours/day and continued if no progression in the abdominal or pelvic regions (‘in-field region’) per RECIST V1.1. Clinical follow-up will be performed q4w, with radiological follow-up (CT or MRI scans of the abdomen and chest) q8w. The primary endpoint is overall survival. Secondary endpoints: PFS, objective response rate, AEs, and quality of life (EORTC QLQ-C30 with QLQ-OV28). Sample size (n=540) will detect an increase in median OS from 12 to 16 months (HR 0.75). Data Monitoring Committee (DMC) meeting (March 2020) concluded that data to-date showed no safety issues and recommended trial continuation.

  • phase ib study of mirvetuximab soravtansine a folate receptor alpha frα targeting antibody drug conjugate adc in combination with bevacizumab in patients with platinum resistant Ovarian Cancer
    Gynecologic Oncology, 2020
    Co-Authors: David M Omalley, Lucy Gilbert, Ursula A. Matulonis, Michael J Birrer, I Vergote, Antonio Gonzalez Martin, Cesar M Castro, Lainie P Martin, Gina Mantiasmaldone, Raquel Bratos
    Abstract:

    Abstract Purpose To evaluate the safety and clinical activity of mirvetuximab soravtansine, an antibody-drug conjugate comprising a humanized anti-folate receptor alpha (FRα) monoclonal antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent, in combination with bevacizumab in patients with FRα-positive, Platinum-Resistant Ovarian Cancer. Methods Patients with Platinum-Resistant epithelial Ovarian, fallopian tube, or primary peritoneal Cancer were administered mirvetuximab soravtansine (6 mg/kg, adjusted ideal body weight) and bevacizumab (15 mg/kg) once every 3 weeks. Eligibility included FRα positivity by immunochemistry and prior bevacizumab exposure was permitted. Adverse events, tumor response, and progression-free survival (PFS) were determined. Results Sixty-six patients, with a median of 3 prior lines of therapy (range, 1–8), received the combination of mirvetuximab soravtansine and bevacizumab at full dosing during the escalation and expansion stages of the study. Adverse events were generally mild-to-moderate (≤grade 2) with diarrhea, blurred vision, nausea, and fatigue being the most common treatment-related toxicities. Six cases of pneumonitis (9%; all grade 1 or 2), an adverse event of special interest, were observed. The confirmed objective response rate (ORR) was 39%, including 5 complete responses and 21 partial responses, and the median PFS was 6.9 months. The combination was particularly active in the subset of patients (n = 16) who were bevacizumab-naive, less heavily pretreated (1–2 prior lines), and whose tumors exhibited medium/high FRα expression (ORR, 56% with a median duration of response of 12 months; PFS, 9.9 months). Conclusion The combination of mirvetuximab soravtansine with bevacizumab is well tolerated in patients with Platinum-Resistant, recurrent Ovarian Cancer. The encouraging efficacy measures compare favorably to reported outcomes for bevacizumab combined with standard chemotherapy in similar patient populations.

  • p154 tumor treating fields 200 khz concomitant with weekly paclitaxel for platinum resistant Ovarian Cancer phase 3 innovate engot ov50 study
    International Journal of Gynecologic Cancer, 2019
    Co-Authors: I Vergote, Robert L Coleman, David Cibula, Eleftherios P Samartzis, Jalid Sehouli, Bradley J Monk, Larry J Copeland, Radoslaw Madry, Gonzalez A Martin, Jacob Korach
    Abstract:

    Introduction/Background Tumor Treating Fields (TTFields) are a non-invasive, regional antimitotic therapy. The Phase 2 INNOVATE study [NCT02244502] demonstrated safety of TTFields plus weekly paclitaxel in 31 PROC (Platinum-Resistant Ovarian Cancer) patients (Vergote et al Gyn Onc 2018;150:471). No increase in grade 3–4 TTFields reported; 26 patients (84%) had TTFields-related dermatitis; one patient permanently discontinued TTFields due to dermatitis. Patients received median of 4 prior therapies; 100% prior platinum and 97% prior taxanes. Median PFS was 8.9 months, 25% had partial response and clinical benefit rate was 71%. The median overall survival was not reached: the one-year survival rate was 61%. This phase 3 INNOVATE-3/ENGOT-ov50 study investigates TTFields combined with weekly paclitaxel in PROC patients. Methodology Patients (N=540) will have PROC (per RECIST V1.1) within 6 months of last platinum therapy with a maximum of 2–5 prior lines of systemic therapy, ECOG score of 0–1 and no peripheral neuropathy above grade1. Patients with primary refractory disease (progression during first line therapy) will be excluded. Patients will be randomized 1:1 to either weekly paclitaxel alone or weekly paclitaxel plus TTFields (200 kHz). Weekly paclitaxel will be administered at standard starting of dose 80 mg/m2 weekly for 8 weeks, and then on Days 1, 8, and 15 for subsequent 28-day cycle. TTFields will be delivered for 18 hours/day and continued if no progression in the abdominal or pelvic regions (‘in-field region’) per RECIST V1.1. Clinical follow up will be performed q4w, with radiological follow up (CT or MRI scans of the abdomen and chest) q8w. The primary endpoint is overall survival. Main secondary endpoints: progression-free survival, objective response rate, severity and frequency of AEs, and quality of life (EORTC QLQ-C30 with QLQ-OV28). Sample size (n=540) will detect an increase in median overall survival from 12 to 16 months (Hazard ratio 0.75). Results N/A TiP. Conclusion N/A TiP. Disclosure Ignace Vergote declares: Grants (Amgen and Roche);Consulting and advisory board (Roche, Genmab,Advaxis, Morphotek, Hoffmann-La Roche, Cerculean Pharma Inc., Novocure GmBh, Astrazeneca, Mateon Therapeutics Inc., Immunogen Inc., Eli Lilly Benelux NV, Amgen Inc., Theradex Europe Limited, Pfizer Inc., Debiopharma International SA, Vifor Pharma Belgie, Novartis Pharma AG, MSD Belgium BVBA, Janssen-Cilag, Bayer Pharma AG, Clovis Oncology, Takeda, Pharma Mar, Oncoinvent, − Contracted Research by Morphotek and travel expenses sponsored by Tesaro, Clovis Oncology, Takeda, Pharma Mar, Roche, Genmab and Oncoinvent.

  • penelope ago ovar 2 20 a double blind placebo pla controlled randomized phase iii engot trial evaluating chemotherapy ct with or without pertuzumab p for platinum resistant Ovarian Cancer
    Journal of Clinical Oncology, 2014
    Co-Authors: C Kurzeder, Patricia Pautier, Petronella Ottevanger, Josep M Del Campo, Angiolo Gadducci, I Vergote, Felix Hilpert, Domenica Lorusso, Isabel Bover, Michel Fabbro
    Abstract:

    TPS5613 Background: Adding P to gemcitabine (GEM) for Platinum-Resistant Ovarian Cancer improved progression-free survival (PFS) in a subset of patients (pts) with low tumor HER3 mRNA expression [M...

Rebecca C. Arend - One of the best experts on this subject based on the ideXlab platform.

  • utilizing an interim futility analysis of the oval study vb 111 701 gog 3018 for potential reduction of risk a phase iii double blind randomized controlled trial of ofranergene obadenovec vb 111 and weekly paclitaxel in patients with platinum resistant Ovarian Cancer
    Gynecologic Oncology, 2021
    Co-Authors: Rebecca C. Arend, Jonathan A. Ledermann, Bradley J Monk, Krishnansu S Tewari, Tamar Rachmilewitz Minei, Thomas J Herzog, Kathleen N Moore, Ronnie Shapirafrommer, Angeles Alvarez Secord, Laurence S Freedman
    Abstract:

    Objective Report the results from a preplanned interim analysis of a phase III, double blind, randomized controlled study of ofranergene obadenovec (VB-111), a targeted anti-Cancer gene therapy, in combination with paclitaxel in patients with platinum resistant Ovarian Cancer (PROC). Methods The OVAL (NCT03398655) study is an on-going study where patients are randomly assigned in a 1:1 ratio to weekly paclitaxel 80 mg/m2 with VB-111 or placebo. The protocol specifies a pre-planned unblinded futility interim analysis of CA-125 response per GCIG criteria in the first 60 evaluable patients. The futility rule determined for this analysis was that the response rate of VB-111 must be greater than the response rate of placebo by at least 10% in order to continue the study. Coincident with the interim analysis, the blinded CA-125 response rate was estimated as a proportion of the first 60 evaluable patients with CA-125 response per GCIG criteria. Post-treatment fever is provided as a possible surrogate marker of VB-111 therapy activity. Results The median age of the evaluable patients was 62 years (range 41-82); 97% had high-grade serous Cancer; 58% had been treated with 3 or more previous lines of therapy, 70% received prior anti-angiogenic treatment, 43% received prior PARP inhibitors. CA-125 response in the VB-111 and weekly paclitaxel treated arm met the pre-specified interim criterion of an absolute advantage of 10% or higher compared to the control. Blinded results show a 53% CA-125 response rate (32/60) with 15% complete response (n=9). Assuming balanced randomization and an absolute advantage of 10% or higher to the VB-111 arm, it may be deducted that the response in the VB-111 treatment arm is 58% or higher. Among patients with post-treatment fever, the CA-125 response rate was 69%. Conclusions At the time of the interim analysis, response rate findings are comparable to the responses seen in a similar patient population in the phase I/II study. The independent data and safety monitoring committee (iDSMC) recommended continuing the OVAL trial as planned. No new safety signals were identified.

  • ofranergene obadenovec vb 111 in platinum resistant Ovarian Cancer favorable response rates in a phase i ii study are associated with an immunotherapeutic effect
    Gynecologic Oncology, 2020
    Co-Authors: Rebecca C. Arend, Michael J Birrer, Hannah M Beer, Yael C Cohen, Suzanne Berlin, Susana M Campos, Tamar Rachmilewitz Minei, Dror Harats, Jaclyn A Wall, Mckenzie E Foxall
    Abstract:

    Abstract Objective Report final results of a phase I/II study of VB-111, a targeted anti-Cancer gene therapy with a dual mechanism: anti angiogenic/vascular disruption and induction of an anti-tumor directed immune response, in combination with paclitaxel in patients with Platinum-Resistant Ovarian Cancer. Methods Study NCT01711970 was a prospective, open label, dose escalation study assessing combination treatment of VB-111 and weekly paclitaxel. In the Phase I part of the study, patients were treated with escalating doses of intravenous VB-111 and paclitaxel. In Phase 2, patients were treated with therapeutic doses of VB-111 and paclitaxel 80 mg/m2. Assessments included safety, overall survival (OS), progression free survival (PFS), and tumor response (CA-125 and RECIST). Results 21 patients with recurrent Platinum-Resistant Ovarian Cancer were enrolled. 17/21 received the therapeutic dose. Patients had a median of 3 prior lines of therapy. Half of the subjects were platinum refractory, and half were previously treated with antiangiogenics. No DLTs were observed. VB-111 was well tolerated and associated with mild flu-like symptoms. In the therapeutic dose cohort, a 58% CA-125 GCIG response rate was seen in evaluable patients. The median OS was 16.6 months in patients treated with therapeutic dose compared to 5.8 months in sub-therapeutic dose (p = 0.028). Tumor specimens taken after treatment demonstrated tumor infiltrated with cytotoxic CD8 T-cells in regions of apoptotic Cancer cells. Conclusions Treatment with VB-111 in combination with paclitaxel was safe and well tolerated. Favorable tumor responses and overall survival outcomes were associated with induction of an immunotherapeutic effect.

  • Abstract CT157: An open-label Phase II study of combination of TSR-042, bevacizumab, and niraparib in patients with Platinum-Resistant Ovarian Cancer (OC): Cohort A of the OPAL trial
    Clinical Trials, 2019
    Co-Authors: Joyce F. Liu, Sarah Wang, Camille C. Gunderson, Andrea E. Wahner Hendrickson, Elena Ratner, Elisabeth J. Diver, John W. Moroney, Rebecca C. Arend, Melinda Louie-gao, Katarina Luptakova
    Abstract:

    Background: Most patients with advanced OC relapse after initial standard platinum-based chemotherapy, and eventually the disease becomes Platinum-Resistant. Niraparib (ZEJULA®) was the first selective poly(ADP-ribose) polymerase inhibitor (PARPi) approved in the United States and Europe for maintenance treatment in patients with recurrent OC regardless of BRCA mutation status. Preclinical evidence suggests that niraparib activates the stimulator of interferon genes pathway to increase immune cell infiltration and synergizes with anti-PD-1 therapy. Additionally, hypoxia induces contextual synthetic lethality by impairing homologous recombination, and therefore induction of hypoxia by inhibition of angiogenesis could lead to synergy with PARPi. In the TOPACIO/KEYNOTE-162 trial, niraparib in combination with pembrolizumab has shown efficacy in recurrent, Platinum-Resistant OC. Niraparib in combination with the anti-angiogenic agent bevacizumab is under study for the treatment of recurrent platinum-sensitive OC (AVANOVA trial) and advanced OC following response on frontline platinum-based chemotherapy (OVARIO trial). TSR-042 is an anti-PD-1 humanized monoclonal antibody that has shown clinical activity as monotherapy in early phase trials. Cohort A of the OPAL trial will evaluate the novel triple combination of the PARPi niraparib, angiogenesis inhibitor bevacizumab, and PD-1 inhibitor TSR-042 in patients with Platinum-Resistant OC who are naive to PARPi therapy. Methods: Eligible patients will have high-grade recurrent epithelial Ovarian, fallopian tube, or primary peritoneal Cancer of the ovary and progressed ≤6 months from completion of ≥4 cycles of platinum-based chemotherapy. Additional key eligibility criteria include 1-2 prior lines of antiCancer therapy for OC, no prior therapy with an anti-PD-1 or anti-PD-L1 antibody, and no prior therapy for OC with a PARPi. Patients will receive a combination regimen of 500 mg TSR-042 on day 1 of each 3-week cycle for 4 cycles, then 1000 mg on day 1 of every other cycle beginning on cycle 5 until progression or toxicity, 15 mg/kg bevacizumab on day 1 of each 3-week cycle for up to 15 months, and niraparib 300 mg or 200 mg (for patients Clinical trial identification:NCT03574779 Citation Format: Joyce Liu, Camille Gunderson, Andrea Wahner Hendrickson, Elena Ratner, Elisabeth Diver, John Moroney, Rebecca C. Arend, Melinda Louie-Gao, Sarah Wang, Katarina Luptakova, Gottfried E. Konecny. An open-label Phase II study of combination of TSR-042, bevacizumab, and niraparib in patients with Platinum-Resistant Ovarian Cancer (OC): Cohort A of the OPAL trial [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 CT157.

Bradley J Monk - One of the best experts on this subject based on the ideXlab platform.

  • utilizing an interim futility analysis of the oval study vb 111 701 gog 3018 for potential reduction of risk a phase iii double blind randomized controlled trial of ofranergene obadenovec vb 111 and weekly paclitaxel in patients with platinum resistant Ovarian Cancer
    Gynecologic Oncology, 2021
    Co-Authors: Rebecca C. Arend, Jonathan A. Ledermann, Bradley J Monk, Krishnansu S Tewari, Tamar Rachmilewitz Minei, Thomas J Herzog, Kathleen N Moore, Ronnie Shapirafrommer, Angeles Alvarez Secord, Laurence S Freedman
    Abstract:

    Objective Report the results from a preplanned interim analysis of a phase III, double blind, randomized controlled study of ofranergene obadenovec (VB-111), a targeted anti-Cancer gene therapy, in combination with paclitaxel in patients with platinum resistant Ovarian Cancer (PROC). Methods The OVAL (NCT03398655) study is an on-going study where patients are randomly assigned in a 1:1 ratio to weekly paclitaxel 80 mg/m2 with VB-111 or placebo. The protocol specifies a pre-planned unblinded futility interim analysis of CA-125 response per GCIG criteria in the first 60 evaluable patients. The futility rule determined for this analysis was that the response rate of VB-111 must be greater than the response rate of placebo by at least 10% in order to continue the study. Coincident with the interim analysis, the blinded CA-125 response rate was estimated as a proportion of the first 60 evaluable patients with CA-125 response per GCIG criteria. Post-treatment fever is provided as a possible surrogate marker of VB-111 therapy activity. Results The median age of the evaluable patients was 62 years (range 41-82); 97% had high-grade serous Cancer; 58% had been treated with 3 or more previous lines of therapy, 70% received prior anti-angiogenic treatment, 43% received prior PARP inhibitors. CA-125 response in the VB-111 and weekly paclitaxel treated arm met the pre-specified interim criterion of an absolute advantage of 10% or higher compared to the control. Blinded results show a 53% CA-125 response rate (32/60) with 15% complete response (n=9). Assuming balanced randomization and an absolute advantage of 10% or higher to the VB-111 arm, it may be deducted that the response in the VB-111 treatment arm is 58% or higher. Among patients with post-treatment fever, the CA-125 response rate was 69%. Conclusions At the time of the interim analysis, response rate findings are comparable to the responses seen in a similar patient population in the phase I/II study. The independent data and safety monitoring committee (iDSMC) recommended continuing the OVAL trial as planned. No new safety signals were identified.

  • 403 phase 3 trial of tumor treating fields concomitant with weekly paclitaxel for platinum resistant Ovarian Cancer engot ov50 gog 329 innovate 3
    International Journal of Gynecologic Cancer, 2020
    Co-Authors: I Vergote, Robert L Coleman, Jalid Sehouli, R Fossati, Bradley J Monk, Larry J Copeland, David M Omalley
    Abstract:

    Introduction/Background Tumor Treating Fields (TTFields) are a non-invasive, antimitotic Cancer therapy. The Phase 2 INNOVATE study demonstrated safety of TTFields/weekly paclitaxel in 31 PROC (Platinum-Resistant Ovarian Cancer) patients (Vergote Gyn Onc 2018); efficacy: median PFS 8.9 months, 25% partial response,71% clinical benefit and 61% 1-year survival rate. This phase 3 ENGOT-ov50/GOG-329/INNOVATE-3 study [NCT03940196] investigates TTFields plus weekly paclitaxel in PROC patients. Methodology Patients (N=540) will have PROC (RECIST V1.1) within 6 months of last platinum therapy with maximum of 2–5 prior lines of systemic therapy, ECOG 0–1 and no peripheral neuropathy >grade1. Patients with primary refractory disease will be excluded. Patients will be randomized 1:1 to weekly paclitaxel alone or weekly paclitaxel (starting of dose 80 mg/m2 weekly for 8 weeks, and then on Days 1, 8, and 15 for subsequent 28-day cycle ) plus TTFields (200 kHz for 18 hours/day and continued if no progression in the abdominal or pelvic regions (‘in-field region’) per RECIST V1.1. Clinical follow-up will be performed q4w, with radiological follow-up (CT or MRI scans of the abdomen and chest) q8w. The primary endpoint is overall survival. Secondary endpoints: PFS, objective response rate, AEs, and quality of life (EORTC QLQ-C30 with QLQ-OV28). Sample size (n=540) will detect an increase in median OS from 12 to 16 months (HR 0.75). Data Monitoring Committee (DMC) meeting (March 2020) concluded that data to-date showed no safety issues and recommended trial continuation. Results TiP N/A Conclusion TiP N/A Disclosures

  • p154 tumor treating fields 200 khz concomitant with weekly paclitaxel for platinum resistant Ovarian Cancer phase 3 innovate engot ov50 study
    International Journal of Gynecologic Cancer, 2019
    Co-Authors: I Vergote, Robert L Coleman, David Cibula, Eleftherios P Samartzis, Jalid Sehouli, Bradley J Monk, Larry J Copeland, Radoslaw Madry, Gonzalez A Martin, Jacob Korach
    Abstract:

    Introduction/Background Tumor Treating Fields (TTFields) are a non-invasive, regional antimitotic therapy. The Phase 2 INNOVATE study [NCT02244502] demonstrated safety of TTFields plus weekly paclitaxel in 31 PROC (Platinum-Resistant Ovarian Cancer) patients (Vergote et al Gyn Onc 2018;150:471). No increase in grade 3–4 TTFields reported; 26 patients (84%) had TTFields-related dermatitis; one patient permanently discontinued TTFields due to dermatitis. Patients received median of 4 prior therapies; 100% prior platinum and 97% prior taxanes. Median PFS was 8.9 months, 25% had partial response and clinical benefit rate was 71%. The median overall survival was not reached: the one-year survival rate was 61%. This phase 3 INNOVATE-3/ENGOT-ov50 study investigates TTFields combined with weekly paclitaxel in PROC patients. Methodology Patients (N=540) will have PROC (per RECIST V1.1) within 6 months of last platinum therapy with a maximum of 2–5 prior lines of systemic therapy, ECOG score of 0–1 and no peripheral neuropathy above grade1. Patients with primary refractory disease (progression during first line therapy) will be excluded. Patients will be randomized 1:1 to either weekly paclitaxel alone or weekly paclitaxel plus TTFields (200 kHz). Weekly paclitaxel will be administered at standard starting of dose 80 mg/m2 weekly for 8 weeks, and then on Days 1, 8, and 15 for subsequent 28-day cycle. TTFields will be delivered for 18 hours/day and continued if no progression in the abdominal or pelvic regions (‘in-field region’) per RECIST V1.1. Clinical follow up will be performed q4w, with radiological follow up (CT or MRI scans of the abdomen and chest) q8w. The primary endpoint is overall survival. Main secondary endpoints: progression-free survival, objective response rate, severity and frequency of AEs, and quality of life (EORTC QLQ-C30 with QLQ-OV28). Sample size (n=540) will detect an increase in median overall survival from 12 to 16 months (Hazard ratio 0.75). Results N/A TiP. Conclusion N/A TiP. Disclosure Ignace Vergote declares: Grants (Amgen and Roche);Consulting and advisory board (Roche, Genmab,Advaxis, Morphotek, Hoffmann-La Roche, Cerculean Pharma Inc., Novocure GmBh, Astrazeneca, Mateon Therapeutics Inc., Immunogen Inc., Eli Lilly Benelux NV, Amgen Inc., Theradex Europe Limited, Pfizer Inc., Debiopharma International SA, Vifor Pharma Belgie, Novartis Pharma AG, MSD Belgium BVBA, Janssen-Cilag, Bayer Pharma AG, Clovis Oncology, Takeda, Pharma Mar, Oncoinvent, − Contracted Research by Morphotek and travel expenses sponsored by Tesaro, Clovis Oncology, Takeda, Pharma Mar, Roche, Genmab and Oncoinvent.

  • pro 105 a phase ii open label study of nuc 1031 in patients with platinum resistant Ovarian Cancer
    Journal of Clinical Oncology, 2018
    Co-Authors: Charlie Gourley, Heather J Dalton, Susana Banerjee, Joseph Buscema, Michelle Lockley, Jonathan Krell, Bradley J Monk
    Abstract:

    TPS5612Background: Patients with Platinum-Resistant Ovarian Cancer, following ≥3 lines of chemotherapy have limited treatment options. NUC-1031, a phosphoramidate transformation of gemcitabine, is ...

Sven Mahner - One of the best experts on this subject based on the ideXlab platform.

  • sorafenib plus topotecan versus placebo plus topotecan for platinum resistant Ovarian Cancer trias a multicentre randomised double blind placebo controlled phase 2 trial
    Lancet Oncology, 2018
    Co-Authors: Radoslav Chekerov, Sven Mahner, Felix Hilpert, Ahmed Elbalat, Philipp Harter, Nikolaus De Gregorio, Claudius Fridrich, Susanne Markmann, Jochem Potenberg
    Abstract:

    Summary Background Antiangiogenic therapy has known activity in Ovarian Cancer. The investigator-initiated randomised phase 2 TRIAS trial assessed the multi-kinase inhibitor sorafenib combined with topotecan and continued as maintenance therapy for Platinum-Resistant or platinum-refractory Ovarian Cancer. Methods We did a multicentre, double-blind, placebo-controlled, randomised, phase 2 trial at 20 sites in Germany. Patients (≥18 years) with Platinum-Resistant Ovarian Cancer previously treated with two or fewer chemotherapy lines for recurrent disease were stratified (first vs later relapse) in block sizes of four and randomly assigned (1:1) using a web-generated response system to topotecan (1·25 mg/m2 on days 1–5) plus either oral sorafenib 400 mg or placebo twice daily on days 6–15, repeated every 21 days for six cycles, followed by daily maintenance sorafenib or placebo for up to 1 year in patients without progression. Investigators and patients were masked to allocation of sorafenib or placebo; topotecan treatment was open label. The primary endpoint was investigator-assessed progression-free survival, analysed in all patients who received at least one dose of study drug. This completed trial is registered with ClinicalTrials.gov , number NCT01047891 . Findings Between Jan 18, 2010, and Sept 19, 2013, 185 patients were enrolled, 174 of whom were randomly assigned: 85 to sorafenib and 89 to placebo. Two patients in the sorafenib group had serious adverse events before treatment and were excluded from analyses. 83 patients in the sorafenib group and 89 in the placebo group started treatment. Progression-free survival was significantly improved with sorafenib versus placebo (hazard ratio 0·60, 95% CI 0·43–0·83; p=0·0018). Median progression-free survival was 6·7 months (95% CI 5·8–7·6) with sorafenib versus 4·4 months (3·7–5·0) with placebo. The most common grade 3–4 adverse events were leucopenia (57 [69%] of 83 patients in the sorafenib group vs 47 [53%] of 89 in the placebo group), neutropenia (46 [55%] vs 48 [54%]), and thrombocytopenia (23 [28%] vs 20 [22%]). Serious adverse events occurred in 49 (59%) of 83 sorafenib-treated patients and 45 (51%) of 89 placebo-treated patients. Of these, events were fatal in four patients (5%) in the sorafenib group (dyspnoea and poor general condition, septic shock, ascites and dyspnoea, and sigma perforation) and seven (8%) in the placebo group (pulmonary embolism in two patients, disease progression in two patients, and one case each of sepsis with fever, pleural effusion, and tumour cachexia). Sorafenib was associated with increased incidences of grade 3 hand-foot skin reaction (three [13%] vs 0 patients) and grade 2 alopecia (24 [29%] vs 12 [13%]). Interpretation Sorafenib, when given orally in combination with topotecan and continued as maintenance therapy, showed a statistically and clinically significant improvement in progression-free survival in women with Platinum-Resistant Ovarian Cancer. These encouraging results support the crucial role of antiangiogenesis as the treatment backbone in combination with chemotherapy, making this approach attractive for further assessment with other targeted strategies. Funding Bayer , Amgen , and GlaxoSmithKline .

  • pertuzumab plus chemotherapy for platinum resistant Ovarian Cancer safety run in results of the penelope trial
    International Journal of Gynecological Cancer, 2016
    Co-Authors: Antonio Gonzalezmartin, Nicoletta Colombo, Patricia Pautier, Sven Mahner, Petronella Ottevanger, Josep M Del Campo, Frederic Selle, Andreas Du Bois, Angiolo Gadducci, Yolanda Garcia Garcia
    Abstract:

    Objective In Platinum-Resistant Ovarian Cancer, adding pertuzumab to gemcitabine improved progression-free survival in the subgroup with low tumor HER3 messenger RNA expression. The 2-part PENELOPE trial (NCT01684878) is prospectively investigating pertuzumab plus chemotherapy in this population. Patients and Methods Part 1 evaluated pertuzumab plus either topotecan or paclitaxel. Patients with platinum-refractory or Platinum-Resistant recurrent Ovarian, primary peritoneal, or fallopian tube Cancer and low HER3 messenger RNA expression (concentration ratio ≤2.81 by central quantitative reverse transcriptase-polymerase chain reaction testing on Cobas z480) received intravenous pertuzumab (840 mg loading dose then 420 mg every 3 weeks) with the investigator’s choice of topotecan (1.25 mg/m2 days 1–5 every 3 weeks) or weekly paclitaxel (80 mg/m2) until disease progression or unacceptable toxicity. The primary objective was to assess safety and tolerability. Results Fifty patients were treated in part 1 (22 topotecan; 28 paclitaxel). In both cohorts, disease progression was the most common primary reason for discontinuing pertuzumab, and the most common all-grade adverse events (AEs) were fatigue/asthenia, anemia, and diarrhea. The most common grade ≥3 AEs were anemia (36%), neutropenia (27%), and fatigue/asthenia (18%) for topotecan, and peripheral sensory neuropathy (14%) and anemia (11%) for paclitaxel. Two patients receiving paclitaxel-pertuzumab died from AEs (abdominal infection; unexplained death). Median progression-free survival was 4.1 months (95% confidence interval, 1.9–6.1) with topotecan-pertuzumab and 4.2 months (95% confidence interval, 3.5–6.0) with paclitaxel-pertuzumab. Conclusions Based on part 1 tolerability, the Independent Data Monitoring Committee had no objection to PENELOPE proceeding to part 2, a double-blind randomized comparison of chemotherapy (topotecan, paclitaxel, or gemcitabine) plus pertuzumab or placebo.

  • pertuzumab p plus chemotherapy ct for platinum resistant Ovarian Cancer safety run in results of the penelope trial
    Journal of Clinical Oncology, 2014
    Co-Authors: Antonio Gonzalezmartin, Nicoletta Colombo, Patricia Pautier, Sven Mahner, Petronella Ottevanger, Josep M Del Campo, Andreas Du Bois, Dominique Bertonrigaud, Ulrich Freudensprung, Ruamir Walker
    Abstract:

    5552 Background: In Platinum-Resistant Ovarian Cancer, the monoclonal antibody P, which inhibits HER2 heterodimerization, improved PFS when added to gemcitabine in the subgroup of pts with low tumor HER3 mRNA expression [Makhija, 2010]. The 2-part PENELOPE trial (NCT01684878) is prospectively investigating P added to single-agent CT in this population. Methods: Part 1 (safety run-in) of PENELOPE evaluated P + either topotecan (TOP) or paclitaxel (PAC). Pts with platinum-refractory or -resistant recurrent Ovarian, primary peritoneal, or fallopian tube Cancer (progression [PD] during or within 6 mo of completing ≥4 platinum cycles) and low HER3 mRNA expression (concentration ratio ≤2.81 by central qRT-PCR testing on cobas z480) received IV P 840→420 mg q3w + investigator’s choice of TOP (1.25 mg/m² d1–5 q3w; cohort 1) or PAC (80 mg/m2 d1, 8, 15 q3w; cohort 2) until PD or unacceptable toxicity. The primary objective was to assess safety and tolerability. After all pts had received ≥3 cycles, the Independent ...

  • topotecan weekly versus conventional 5 day schedule in patients with platinum resistant Ovarian Cancer a randomized multicenter phase ii trial of the north eastern german society of gynecological oncology Ovarian Cancer study group
    Journal of Clinical Oncology, 2011
    Co-Authors: Jalid Sehouli, Sven Mahner, Philipp Harter, Susanne Markmann, Dirk Stengel, Christian Kurzeder, A Belau, Thomas Bogenrieder, Lothar Mueller, R Lorenz
    Abstract:

    Purpose Weekly administration of topotecan (Tw) is less toxic and widely considered a better treatment option than conventional 5-day therapy (Tc) in women with Platinum-Resistant recurrent Ovarian Cancer. We conducted a randomized phase II trial (TOWER [Topotecan Weekly Versus Conventional 5-Day Schedule in Patients With Platinum-Resistant Ovarian Cancer]) to better define the ratio between benefits and risks with either treatment approach. Patients and Methods Patients were randomly assigned to two independent two-stage protocols of Tw (4 mg/m2/wk administered on days 1, 8, and 15) or Tc (1.25 mg/m2/d on days 1 to 5). We evaluated risk ratios (RRs) for the primary end point of clinical benefit (complete response, partial response, and stable disease), the duration of progression-free survival (PFS) and overall survival (OS), associated hazard ratios (HRs), and RRs of toxicity with 95% CIs. Results In total, 194 patients were randomly assigned at 54 centers to Tw (n = 97) or Tc (n = 97). Clinical benefit...

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