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Michael W. Sill - One of the best experts on this subject based on the ideXlab platform.

Ana Gabriela M. Fontana - One of the best experts on this subject based on the ideXlab platform.

  • a phase ii trial with anti lewis y monoclonal antibody hu3s193 for the treatment of platinum resistant refractory ovarian fallopian tube and Primary Peritoneal Carcinoma
    Gynecologic Oncology, 2015
    Co-Authors: Oren Smaletz, Maria Del Pilar Estevez Diz, Claudio Calazan Do Carmo, Jorge Sabbaga, Sergio J. Azevedo, Fernando Cotait Maluf, Carlos H. Barrios, Ronaldo L. Costa, Geraldo F Cunhajunior, Ana Gabriela M. Fontana
    Abstract:

    Abstract Objectives The Primary objective was to evaluate the clinical efficacy of hu3S193, a humanized monoclonal antibody against the Lewis-Y antigen, in patients with platinum resistant/refractory ovarian, fallopian tube and Primary Peritoneal Carcinoma. Secondary objectives were safety and pharmacokinetics. In addition, we sought to determine the potential interaction of clinical benefit and patient characteristics. Methods This two-stage, multicenter, single arm, phase II trial enrolled eligible patients to receive hu3S193 weekly at a dose of 20 mg/m2 intravenously for 8 weeks (1 cycle) to a maximum of 3 cycles. Efficacy was measured as clinical benefit rate (objective response or stable disease for at least 24 weeks). Results 26 of 31 patients were eligible for efficacy analysis. No complete/partial responses were observed. Six patients had stable disease for 24 + weeks [clinical benefit rate 23% (95% CI = 9.77%–46.71%)]. Median PFS was 8.4 weeks (95% CI = 6.0 to 16.1). Median PFS differed between patients with no ascites and no visceral disease and patients with ascites and/or visceral disease [16.1 vs. 8.1 weeks (p = 0.0058)]. The most commonly reported treatment-related adverse events were fatigue (19.3%) and nausea (16.2%). Allergic reactions occurred in 6 patients (5 with Grade 1/2; 1 with Grade 3). Conclusions Hu3S193 lacked sufficient activity in the first stage of the study to open enrollment to the second stage. However, based on the longer PFS in patients with no ascites and no visceral disease, consolidation strategies in platinum sensitive disease are currently being tested.

  • A phase II trial with anti-Lewis-Y monoclonal antibody (hu3S193) for the treatment of platinum resistant/refractory ovarian, fallopian tube and Primary Peritoneal Carcinoma
    Gynecologic oncology, 2015
    Co-Authors: Oren Smaletz, Maria Del Pilar Estevez Diz, Claudio Calazan Do Carmo, Jorge Sabbaga, Geraldo F. Cunha-junior, Sergio J. Azevedo, Fernando Cotait Maluf, Carlos H. Barrios, Ronaldo L. Costa, Ana Gabriela M. Fontana
    Abstract:

    Abstract Objectives The Primary objective was to evaluate the clinical efficacy of hu3S193, a humanized monoclonal antibody against the Lewis-Y antigen, in patients with platinum resistant/refractory ovarian, fallopian tube and Primary Peritoneal Carcinoma. Secondary objectives were safety and pharmacokinetics. In addition, we sought to determine the potential interaction of clinical benefit and patient characteristics. Methods This two-stage, multicenter, single arm, phase II trial enrolled eligible patients to receive hu3S193 weekly at a dose of 20 mg/m2 intravenously for 8 weeks (1 cycle) to a maximum of 3 cycles. Efficacy was measured as clinical benefit rate (objective response or stable disease for at least 24 weeks). Results 26 of 31 patients were eligible for efficacy analysis. No complete/partial responses were observed. Six patients had stable disease for 24 + weeks [clinical benefit rate 23% (95% CI = 9.77%–46.71%)]. Median PFS was 8.4 weeks (95% CI = 6.0 to 16.1). Median PFS differed between patients with no ascites and no visceral disease and patients with ascites and/or visceral disease [16.1 vs. 8.1 weeks (p = 0.0058)]. The most commonly reported treatment-related adverse events were fatigue (19.3%) and nausea (16.2%). Allergic reactions occurred in 6 patients (5 with Grade 1/2; 1 with Grade 3). Conclusions Hu3S193 lacked sufficient activity in the first stage of the study to open enrollment to the second stage. However, based on the longer PFS in patients with no ascites and no visceral disease, consolidation strategies in platinum sensitive disease are currently being tested.

Ursula A. Matulonis - One of the best experts on this subject based on the ideXlab platform.

  • A phase II study of ramucirumab (IMC-1121B) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or Primary Peritoneal Carcinoma
    Gynecologic oncology, 2014
    Co-Authors: Richard T. Penson, K. Moore, Gini F. Fleming, Patricia S. Braly, Veronica L. Schimp, Hoa Nguyen, Ursula A. Matulonis, Susana Banerjee, Paul Haluska, Martin Gore
    Abstract:

    article i nfo Resistant Objective.Vascular endothelialgrowth factor(VEGF)receptor-mediatedsignaling contributes to ovariancan- cer pathogenesis. Elevated VEGF expression is associated with poor clinical outcomes. We investigated ramucirumab, a fully human anti-VEGFR-2 antibody, in patients with persistent or recurrent epithelial ovarian, fallopian tube, or Primary Peritoneal Carcinoma. Primary endpoints were progression-free survival at 6 months (PFS-6) and confirmed objective response rate (ORR). Methods. Women who received ≥1 platinum-based chemotherapeutic regimen and had a platinum-free in- terval of b12 months with measurable disease were eligible. Patients received 8 mg/kg ramucirumab intrave- nously every 2 weeks. Results. Sixty patients were treated; one patient remained on study as of September 2013. The median age was 62 years (range: 27-80), and median number of prior regimens was 3. Forty-five (75%) patients had plati- num refractory/resistant disease. Thirty-nine patients (65.0%) had serous tumors. PFS-6 was 25.0% (n = 15/60, 95% CI: 14.7-37.9%). Best overall response was: partial response 5.0% (n = 3/60), stable disease 56.7% (n = 34/60), and progressive disease 33.3% (n = 20/60). The most common treatment-emergent adverse events possibly related to study drug were headache (65.0%; 10.0% Grade ≥3), fatigue (56.7%; 3.3% Grade ≥3), diarrhea (28.3%; 1.7% Grade ≥3), hypertension (25.0%; 3.3% Grade ≥3), and nausea (20.0%; no Grade ≥3). Two

  • Phase II study of MLN8237 (alisertib), an investigational Aurora A kinase inhibitor, in patients with platinum-resistant or -refractory epithelial ovarian, fallopian tube, or Primary Peritoneal Carcinoma
    Gynecologic oncology, 2012
    Co-Authors: Ursula A. Matulonis, Sudarshan Sharma, Sharad A. Ghamande, Michael S. Gordon, Salvatore A. Del Prete, Isabelle Ray-coquard, Elzbieta Kutarska, Hua Liu, Howard Fingert, Xiaofei Zhou
    Abstract:

    Abstract Objectives Aurora A kinase (AAK), a key mitotic regulator, is implicated in the pathogenesis of several tumors, including ovarian cancer. This single-arm phase II study assessed single-agent efficacy and safety of the investigational AAK inhibitor MLN8237 (alisertib), in patients with platinum-refractory or ‐resistant epithelial ovarian, fallopian tube, or Primary Peritoneal Carcinoma. Methods Adult women with malignant, platinum-treated disease received MLN8237 50mg orally twice daily for 7days plus 14days' rest (21-day cycles). The Primary endpoint was combined objective tumor response rate per Response Evaluation Criteria in Solid Tumors (RECIST) and/or CA-125 criteria. Secondary endpoints included response duration, clinical benefit rate, progression-free survival (PFS), time-to-progression (TTP), and safety. Results Thirty-one patients with epithelial ovarian (n=25), Primary Peritoneal (n=5), and fallopian tube Carcinomas (n=1) were enrolled. Responses of 6.9–11.1month duration were observed in 3 (10%) patients with platinum-resistant ovarian cancer. Sixteen (52%) patients achieved stable disease with a mean duration of response of 2.86months and which was durable for ≥3months in 6 (19%). Median PFS and TTP were 1.9months. Most common drug-related grade ≥3 adverse events were neutropenia (42%), leukopenia (23%), stomatitis, and thrombocytopenia (each 19%); 6% reported febrile neutropenia. Conclusions These data suggest that MLN8237 has modest single-agent antitumor activity and may produce responses and durable disease control in some patients with platinum-resistant ovarian cancer. MLN8237 is currently undergoing evaluation in a phase I/II trial with paclitaxel in recurrent ovarian cancer.

Robert S. Mannel - One of the best experts on this subject based on the ideXlab platform.

  • Phase II evaluation of dasatinib in the treatment of recurrent or persistent epithelial ovarian or Primary Peritoneal Carcinoma: a Gynecologic Oncology Group study.
    Gynecologic oncology, 2012
    Co-Authors: Russell J. Schilder, William E. Brady, Heather A. Lankes, Robert S. Mannel, Harsh B. Pathak, James V Fiorica, Mark S Shahin, Xun C Zhou, R Katherine Alpaugh
    Abstract:

    Preclinical data suggest an important role for the sarcoma proto-oncogene tyrosine kinase (SRC) in the oncogenesis of epithelial ovarian cancer (EOC) or Primary Peritoneal Carcinoma (PPC). The Gynecologic Oncology Group (GOG) conducted a Phase II trial to evaluate the efficacy and safety of dasatinib, an oral SRC-family inhibitor in EOC/PPC, and explored biomarkers for possible association with clinical outcome. Eligible women had measurable, recurrent or persistent EOC/PPC and had received one or two prior regimens which must have contained a platinum and a taxane. Patients were treated with 100mg orally daily of dasatinib continuously until progression of disease or adverse effects prevented further treatment. Primary endpoints were progression-free survival (PFS)≥6months and response rate. Serial plasma samples were assayed for multiple biomarkers. Circulating free DNA was quantified as were circulating tumor and endothelial cells. Thirty-five (35) patients were enrolled in a two-stage sequential design. Of the 34 eligible and evaluable patients, 20.6% (90% confidence interval: 10.1%, 35.2%) had a PFS≥6months; there were no objective responses. Grade 3-4 toxicities were gastrointestinal (mostly nausea and emesis; n=4), pulmonary (dyspnea and/or pleural effusion; n=4) and pain (n=5), and infrequent instances of anemia, malaise, insomnia, rash, and central nervous system hemorrhage. Lack of clinical activity limited any correlation of biomarkers with outcome. Dasatinib has minimal activity as a single-agent in patients with recurrent EOC/PPC. Copyright © 2012. Published by Elsevier Inc.

  • A phase I study with an expanded cohort to assess the feasibility of intravenous paclitaxel, intraPeritoneal carboplatin and intraPeritoneal paclitaxel in patients with untreated ovarian, fallopian tube or Primary Peritoneal Carcinoma: a Gynecologic
    Gynecologic oncology, 2011
    Co-Authors: Natalie S. Gould, Michael W. Sill, Robert S. Mannel, Premal H. Thaker, Paul Disilvestro, Steve Waggoner, S. Diane Yamada, Deborah K. Armstrong, Lari Wenzel, Helen Q. Huang
    Abstract:

    Objective To define the maximum tolerated dose (MTD) and assess the feasibility of intravenous (IV) paclitaxel, intraPeritoneal (IP) carboplatin, and IP paclitaxel in women with newly diagnosed Stages II–IV ovarian, fallopian tube, or Primary Peritoneal Carcinoma.

  • A phase II evaluation of lapatinib in the treatment of persistent or recurrent epithelial ovarian or Primary Peritoneal Carcinoma: a gynecologic oncology group study.
    Gynecologic oncology, 2011
    Co-Authors: Agustin A Garcia, Michael W. Sill, Heather A. Lankes, Robert S. Mannel, Deborah K. Armstrong, Andrew K Godwin, Robert L Carolla, Marcia K Liepman, Nick M Spirtos, Edgar G Fischer
    Abstract:

    Activation and dimerization of the ERBB family play a role in the pathogenesis and progression of ovarian cancer. We conducted a phase II trial to evaluate the activity and tolerability of lapatinib in patients with recurrent or persistent epithelial ovarian cancer (EOC) and to explore the clinical value of expression levels of epidermal growth factor receptors (EGFR), phosphorylated EGFR, HER-2/neu, and Ki-67, and the presence of EGFR mutations. Eligible patients had recurrent or persistent EOC or Primary Peritoneal Carcinoma, measurable disease, and up to 2 prior chemotherapy regimens for recurrent disease. Patients were treated with lapatinib 1500 mg/day. The Primary endpoint of efficacy was 6-month progression free survival (PFS). Twenty-five of 28 patients were eligible and evaluable for analysis of efficacy and toxicity. Two (8.0%) were alive and progression-free at 6 months. No objective responses were observed. There were 1 grade 4 toxicity (fatigue) and few grade 3 toxicities. Associations between Ki-67 with prior platinum-free interval, PFS, and a polymorphism in EGFR were suggested. Lapatinib has minimal activity in recurrent ovarian cancer. Ki-67 expression may be associated with prior PFS and a polymorphism in EGFR exon 20 (2361G>A, Q787Q). Copyright © 2011. Published by Elsevier Inc.

  • Phase I feasibility study of intraPeritoneal cisplatin and intravenous paclitaxel followed by intraPeritoneal paclitaxel in untreated ovarian, fallopian tube, and Primary Peritoneal Carcinoma: A gynecologic oncology group study
    Gynecologic oncology, 2011
    Co-Authors: Don S. Dizon, Stephen C. Rubin, Michael W. Sill, Natalie S. Gould, Robert S. Mannel, S. Diane Yamada, Robert L. Debernardo, Eric L. Eisenhauer, Linda R. Duska, Paula M. Fracasso
    Abstract:

    Purpose IntraPeritoneal chemotherapy has shown a survival advantage over intravenous chemotherapy for women with newly diagnosed optimally debulked epithelial ovarian, fallopian tube, or Primary Peritoneal Carcinoma. However, significant toxicity has limited its acceptance. In an effort to reduce toxicity, the Gynecologic Oncology Group conducted a Phase I study to evaluate the feasibility of day 1 intravenous (IV) paclitaxel and intraPeritoneal (IP) cisplatin followed by day 8 IP paclitaxel on an every 21-day cycle.

Lise Grupe Larsen - One of the best experts on this subject based on the ideXlab platform.

  • Primary Peritoneal Carcinoma: a rare neoplasm with pleomorphic trophoblastic morphology.
    APMIS, 2006
    Co-Authors: Charlotte Winther Madsen, Jane Preuss Hasselby, Lise Grupe Larsen
    Abstract:

    We report a case of Primary Peritoneal Carcinoma with trophoblastic morphology in a 78-year-old woman, diagnosed by histological and immunohistochemical analysis of surgically resected specimens, including the omentum and part of the small bowel. Microscopically, the resected specimens showed diffuse infiltration of a poorly differentiated tumor. Numerous large, often multinucleated cells were seen, and mitotic figures were frequent. Immunohistochemical staining showed a positive reaction for most cytokeratins, EP4, EMA, CA-125, Glut1, WT1, β-hCG and PLAP. We reached a diagnosis of Primary Peritoneal Carcinoma with trophoblastic morphology. To our knowledge this morphology of a Primary Peritoneal Carcinoma has not been described previously.

  • Primary Peritoneal Carcinoma: a rare neoplasm with pleomorphic trophoblastic morphology.
    APMIS : acta pathologica microbiologica et immunologica Scandinavica, 2006
    Co-Authors: Charlotte Winther Madsen, Jane Preuss Hasselby, Lise Grupe Larsen
    Abstract:

    We report a case of Primary Peritoneal Carcinoma with trophoblastic morphology in a 78-year-old woman, diagnosed by histological and immunohistochemical analysis of surgically resected specimens, including the omentum and part of the small bowel. Microscopically, the resected specimens showed diffuse infiltration of a poorly differentiated tumor. Numerous large, often multinucleated cells were seen, and mitotic figures were frequent. Immunohistochemical staining showed a positive reaction for most cytokeratins, EP4, EMA, CA-125, Glut1, WT1, beta-hCG and PLAP. We reached a diagnosis of Primary Peritoneal Carcinoma with trophoblastic morphology. To our knowledge this morphology of a Primary Peritoneal Carcinoma has not been described previously.