Oxaliplatin or Paclitaxel in Patients With Platinum-Pretreated Advanced Ovarian Cancer: A Randomized Phase II Study of the European Organization for Research and Treatment of Cancer Gynecology Group

2000 ◽  
Vol 18 (6) ◽  
pp. 1193-1202 ◽  
Author(s):  
Martine J. Piccart ◽  
John A. Green ◽  
Angel Jimenez Lacave ◽  
Nick Reed ◽  
Ignace Vergote ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Advanced Ovarian Cancer ◽  
Time To Progression ◽  
European Organization ◽  
Randomized Phase Ii ◽  
Grade 3

PURPOSE: This was a multicentric, open, randomized, phase II study of single-agent paclitaxel and oxaliplatin to evaluate the efficacy of oxaliplatin in a relapsing progressive ovarian cancer patient population and to analyze the safety profile and impact of both agents on quality of life, time to progression, and survival. PATIENTS AND METHODS: Eighty-six patients with platinum-pretreated advanced ovarian cancer were randomly assigned to two arms: 41 received paclitaxel at 175 mg/m2 over 3 hours every 3 weeks, and 45 received oxaliplatin at 130 mg/m2 over 2 hours every 3 weeks. For inclusion, patients had to have a performance status of 0 to 2 and to have received at least one and no more than two prior cisplatin- and/or carboplatin-containing chemotherapy regimens within the last 12 months. RESULTS: Seven confirmed responses were observed in each arm, for an overall response rate in the total treated population of 17% (95% confidence interval [CI], 7% to 32%) in the paclitaxel arm and 16% (95% CI, 7% to 29%) in the oxaliplatin arm. Median time to progression was 14 weeks and 12 weeks, and overall survival was 37 weeks and 42 weeks in the paclitaxel and oxaliplatin arms, respectively. Among 63 patients with a 0- to 6-month progression-free, platinum-free interval, there were five objective responses with paclitaxel in 31 patients and two objective responses with oxaliplatin in 32 patients. Nine patients (22%) in the paclitaxel arm had grade 3 or 4 neutropenia (National Cancer Institute of Canada [NCIC] Common Toxicity Criteria). Two patients (4%) experienced grade 3 thrombocytopenia in the oxaliplatin arm. Maximum grade (grade 3) NCIC neurosensory toxicity was experienced by three patients (7%) in the paclitaxel arm and by four patients (9%) in the oxaliplatin arm. CONCLUSION: Single-agent oxaliplatin at 130 mg/m2 every 3 weeks is active with moderate toxicity in patients with cisplatin-/carboplatin-pretreated advanced ovarian cancer.

Phase II study of bortezomib with cisplatin as first-line treatment of malignant pleural mesothelioma (MPM): EORTC 08052.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7081-7081 ◽  
Author(s):  
Mary O'Brien ◽  
Rabab Mohamed Gaafar ◽  
Sanjaykumar Popat ◽  
Francesco Grossi ◽  
Allan Price ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Dose Intensity ◽  
Line Treatment ◽  
First Line ◽  
Phase Ii Studies ◽  
Grade 3 ◽  
First Line Treatment

7081 Background: Cisplatin is one of the most active drugs available in MPM while bortezomib has shown some activity in single agent phase II studies against MPM. This was a prospective phase II study of cisplatin and bortezomib (CB) in the first line treatment of MPM. Methods: Patients with histological proven MPM, with performance status (PS) 0/1, were eligible. The doses were cisplatin 75mg/m2 /3 wks and bortezomib 1.3mg/m2 day 1, 4, 8, 11 every 3 wks. The primary end-point was progression free survival rate at 18 wks (PFSR=18). The 2-stage Simon design (a=0.1; b = 0.05, P0=0.50 and P1=0.675) was used. In the first step of the study 37 eligible patients were planned. If more than 19 patients were alive and free of progression at 18 wks the total sample size was increased to 76 eligible patients. Results: Between 2007 and 2010 82 patients were entered. The median follow-up time is 32.3 months The median age was 55 years (range: 22-77yrs), male/female: 55/27 , PS 0/1: 9/73, Stage T1: 10%; T2: 42%, T3: 25%; T4: 23% and N0: 57%; N1: 4%; N2: 33%; N3: 6%. The median number of cycles received was 4 and 38% received 6 cycles. Cisplatin/ bortezomib dose intensity was 98/ 80%. Toxicity (grade 3/4): neutropenia 10%, thrombocytopenia 11%, anaemia 1%. Grade 3-4 hyponatraemia/ hypokalaemia occurred in 46/ and 17%. Grade 2 tinnitus, grade 3 fatigue occurred in 16%, and 12%, of patients. Motor/sensory/other neurotoxicity was grade 1: 6/28/7%, grade 2: 2/26/2% and grade 3: 1/7/2% respectively. There were 2 toxic deaths at 32 and 74 days due to acute pneumonitis and cardiac arrest. The PFRS-18 (including symptomatic progression) was 53% (80% confidence intervals, CI, 42-64%). The overall survival was 13.5 months (95% CI 10.5-15) with 56% (95% CI 44-66%) alive at 1 year. The PFS was 5.1 months (95% CI 3.3-6.5). Conclusions: On the basis of the PFRS-18, the null hypothesis could not be rejected, although CB gave predictable toxicity and was as active as other reported regimens in MPM.

Sorafenib and continued erlotinib or sorafenib alone in patients with advanced non-small cell lung cancer progressing on erlotinib: A randomized phase II study of the Sarah Cannon Research Institute (SCRI).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7587-7587 ◽  
Author(s):  
Victor Gian ◽  
Mark S. Rubin ◽  
Dianna Shipley ◽  
Howard A. Burris ◽  
Joseph Kaplan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Factor ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Single Agent ◽  
Small Cell ◽  
Small Cell Lung ◽  
Randomized Phase Ii ◽  
Grade 3

7587 Background: Erlotinib is an oral epidermal growth factor receptor kinase inhibitor used in the treatment of advanced non-small-cell lung cancer (NSCLC). Resistance develops in patients (pts) who initially respond to erlotinib leading to progressive disease (PD). Sorafenib is an oral inhibitor of vascular endothelial and platelet-derived growth factor receptors and Raf kinases which play important roles in PD. This randomized phase II study evaluated the role of sorafenib and continued erlotinib or sorafenib alone in pts with progressive NSCLC following initial benefit with erlotinib. Methods: Eligible pts had IIIB/IV NSCLC, an ECOG PS 0-2, and had received ≤2 lines of therapy with the last being single-agent erlotinib. Pts must have PD following clinical benefit (complete/partial response/stable disease) from erlotinib for >8 weeks. Pts were randomized 1:1 to continue erlotinib at the dose administered at the time of PD with the addition of sorafenib 400 mg orally twice daily (Arm A) or to sorafenib alone (Arm B). Cycles were 28 days with restaging every 2 cycles. The primary endpoint was progression-free survival (PFS). Results: 52 pts were enrolled from 2/2008 to 3/2011 (A 24; B 28). Baseline characteristics were balanced between arms and included: median age 65 years (41-87); 65% female; 69% adenocarcinoma/large cell; and 96% PS <2. 41% of pts were either never smokers or smoked <100 cigarettes/lifetime. Pts received a median of 8 weeks of treatment per arm (0.6–67 weeks). The median PFS was 3.1 (95% CI 1.7-3.7) and 2.3 (1.7-3.6) months for A and B, respectively (p=.84). There were no grade 3/4 hematologic toxicities in either arm except grade 3 anemia in 1 pt (A). Severe nonhematologic toxicities in >5% included: fatigue 17%(A)/7%(B); diarrhea 17%/0; dehydration 13%/7%; hand-foot skin reaction 8%/8%, and anorexia 4%/7%. Conclusions: Sorafenib has modest activity when used in combination with erlotinib or as a single agent in pts with PD following benefit with erlotinib alone. Additional study to identify potential subsets of refractory pts who might derive the greatest benefit from sorafenib are warranted.

A randomized phase II study of bevacizumab versus bevacizumab plus lomustine versus lomustine single agent in recurrent glioblastoma: The Dutch BELOB study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2001-2001 ◽  
Author(s):  
Walter Taal ◽  
Hendrika M Oosterkamp ◽  
Annemiek M.E. Walenkamp ◽  
Laurens Victor Beerepoot ◽  
Monique Hanse ◽  
...  
Keyword(s):  
Phase Ii ◽  
Combination Treatment ◽  
Phase Ii Study ◽  
Controlled Trial ◽  
Performance Status ◽  
Single Agent ◽  
Recurrent Glioblastoma ◽  
Controlled Study ◽  
Hematological Toxicity ◽  
Randomized Phase Ii

2001 Background: Bevacizumab (BEV) is widely used in recurrent glioblastoma, alone or in combination with other agents. There is however no well-controlled trial to support the use for this indication. Methods: In a three-arm Dutch multicenter randomized phase II study (NTR 1929) patients were assigned to either BEV 10 mg/kg iv every 2 weeks, BEV 10 mg/kg iv every 2 weeks and 110 mg/m2 lomustine every 6 weeks, or lomustine 110 mg/m2every 6 weeks. Eligible were patients with histologically proven glioblastoma, with a first recurrence after chemo-irradiation with temozolomide, having concluded radiotherapy more than 3 months ago, with adequate bone marrow, renal and hepatic function, and WHO performance status (PS) 0-2. Primary endpoint was 9 months overall survival (OS); P0 was set at 35% and P1 at 55%. Progression was defined using RANO criteria. A safety review after the first 10 patients in the combination arm was preplanned. Results: Between December 2009 and November 2011, 153 patients were enrolled of whom 148 were considered eligible. Median age was 57 years (range, 24-77) and median WHO PS was 1. With respect to prognostic factors groups were well balanced. After review of the safety cohort the dosage lomustine in the combination arm was lowered to 90 mg/m2 because of hematological toxicity (predominantly thrombocytopenia without symptoms). At this lower lomustine dose level the combination treatment was in general well tolerated. Outcome: see Table. Conclusions: In this first well-controlled study on BEV in recurrent glioblastoma with a primary OS endpoint, combination treatment with bevacizumab and lomustine met the prespecified criterion for further investigation in clinical trials, whereas both drugs given as single agent failed to meet this criterion. Clinical trial information: NTR1929. [Table: see text]

Paclitaxel/carboplatin with or without sorafenib in the first-line treatment of patients with stage III/IV epithelial ovarian cancer: A randomized phase II study of the Sarah Cannon Research Institute.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5513-5513
Author(s):  
Dana Shelton Thompson ◽  
B. Stephens Dudley ◽  
John A. Bismayer ◽  
Victor G. Gian ◽  
William McIver Merritt ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Single Agent ◽  
Angiogenesis Inhibitor ◽  
Stage Iii ◽  
Vegf Receptor ◽  
First Line ◽  
Randomized Phase Ii

5513 Background: The combination of paclitaxel and carboplatin is the most widely used chemotherapy regimen for patients (pts) with advanced ovarian cancer, producing a median survival of approximately 36 months. Recently, the addition of bevacizumab, an angiogenesis inhibitor, has improved progression-free survival (PFS) when compared to paclitaxel/carboplatin alone. Sorafenib is an oral multi-kinase inhibitor with effects on tumor angiogenesis through inhibition of the VEGF receptor. The purpose of this randomized phase II study was to compare efficacy of paclitaxel/carboplatin with and without sorafenib. Methods: Women with histologically confirmed, maximally debulked, previously untreated stage III/IV epithelial ovarian carcinoma were randomized to receive paclitaxel 175 mg/m2and carboplatin AUC 6 (PC) or PC + sorafenib 400 mg PO BID (S). All patients received 6 cycles, given every 3 weeks; pts receiving PC+S continued single agent sorafenib for 52 weeks total. The primary endpoint was 2-year PFS rate. Results: 85 pts were randomized between 1/07 and 10/11 (PC+S 43; PC 42). Pt characteristics were similar between groups, except that more patients with only CA125 elevation received PC+S (65% vs 43%). Overall, 67 pts (79%) completed 6 cycles of chemotherapy (PC+S 74%; PC 83%). More patients stopped PC+S due to toxicity (14% vs 7%). 22 pts (51%) receiving PC+S began single agent S after 6 cycles PC, and 12 pts (28%) completed 52 weeks of S. There was no difference in the 2-year PFS rates: PC+S 40%, PC 39%. Overall survival comparisons were also similar (p = 0.36). Pts receiving PC+S had more grade 3 rash (33% vs 0%) and hand-foot syndrome (9% vs 0%). Conclusions: The addition of sorafenib did not improve the efficacy of standard first-line PC in pts with stage III/IV ovarian carcinoma, and resulted in additional toxicity. Clinical trial information: NCT00390611.

scholarly journals Randomized, Phase II Study Prospectively Evaluating Treatment of Metastatic Esophageal, Gastric, or Gastroesophageal Cancer by Gene Expression of ERCC1: SWOG S1201

2020 ◽  
Vol 38 (5) ◽  
pp. 472-479 ◽  
Author(s):  
Syma Iqbal ◽  
Shannon McDonough ◽  
Heinz-Josef Lenz ◽  
David Ilson ◽  
Barbara Burtness ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Interactive Effects ◽  
Randomized Phase Ii ◽  
Esophagogastric Cancer ◽  
Significant Difference ◽  
Grade 3 ◽  
Ercc1 Expression

PURPOSE Platinum-based therapy is the standard of care in patients who have HER2-negative, advanced esophagogastric cancer (AEGC). Retrospective data suggest that intratumoral ERCC1 levels may determine platinum sensitivity. A randomized, phase II study was performed in patients with AEGC to explore whether the efficacy of a platinum-based therapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) versus a non–platinum-containing regimen of irinotecan and docetaxel (IT) differed according to ERCC1 levels. PATIENTS AND METHODS Overall, 202 untreated patients with HER2-negative AEGC and a Zubrod performance status of 0-1 were evaluated prospectively for mRNA expression of ERCC1 level and then randomly assigned to FOLFOX or IT, stratified by the intratumoral statuses of ERCC1 low (< 1.7) or high (≥ 1.7). Objectives were to assess progression-free survival (PFS) and overall survival (OS) in all patients treated with FOLFOX compared with IT, stratified by low and high ERCC1 levels, and to assess for interactive effects between ERCC1 expression and treatment arm. RESULTS Eighty-six percent of patients had ERCC1 values < 1.7. Thus, evaluation of the ERCC1-high subgroup was limited. Grade ≥ 3 anemia, dehydration, diarrhea, and fatigue were greater in patients with IT. Occurrences of grade ≥ 3 neuropathy and decreased neutrophils were greater in patients with FOLFOX. In all patients, FOLFOX had a statistically superior median PFS compared with IT (5.7 v 2.9 months; hazard ratio, 0.68; P = .02). In patients with ERCC1 levels < 1.7 receiving FOLFOX, PFS and response rate were statistically superior to IT, with no significant difference in OS. CONCLUSION The evaluation of ERCC1 in patients with upper GI tumors was thwarted by an overwhelming predominance of low ERCC1 mRNA expression. Nonetheless, distribution of treatment effects on PFS did not vary with expression. For all patients and for those with low ERCC1 expression, FOLFOX was superior in efficacy to IT.

A randomized phase II study of EMD 121974 in patients (pts) with metastatic melanoma (MM)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8548-8548 ◽  
Author(s):  
K. B. Kim ◽  
A. H. Diwan ◽  
N. E. Papadopoulos ◽  
A. Y. Bedikian ◽  
L. H. Camacho ◽  
...  
Keyword(s):  
Phase Ii ◽  
Clinical Efficacy ◽  
Performance Status ◽  
Single Agent ◽  
Stage Iv ◽  
Melanoma Cells ◽  
Serum Lactate Dehydrogenase ◽  
Ecog Performance Status ◽  
Randomized Phase Ii ◽  
Grade 3

8548 Background: EMD 121974 is a selective antagonist of avβ3 integrin, which promotes the proliferation of tumor-associated endothelial cells and potentially the survival of melanoma cells expressing avβ3 integrin. We conducted a randomized phase II trial of cilengitide in pts with MM to evaluate the clinical efficacy at 2 different doses. Methods: Pts with stage IV or unresectable stage III non-choroidal melanoma who had no more than 1 prior systemic therapy were enrolled. Pts at least 18 years of age and with ECOG performance status of 0 to 2 were eligible. All pts underwent baseline tumor biopsy and were randomly assigned to either 500 mg or 2,000 mg intravenous (IV) EMD 121974 twice weekly, using the following stratification factors: 1) prior systemic treatment; 2) visceral metastases; 3) serum lactate dehydrogenase level; 4) tumor avβ3 overexpression, where overexpression is defined as > 25% of melanoma cells staining positive. The primary objective of this study was to determine the progression-free survival rate at 8 weeks. Results: Twenty-nine pts were enrolled, and 26 pts (14 at 500 mg; 12 at 2,000 mg dose) were treated. Patient characteristics for 500 mg and 2,000 mg arm, respectively, are as follows: median age, 57 and 61; percentage (% age) of male, 50% and 50%; % age of ECOG performance status of 0, 79% and 58%; % age of stage IV, 79% and 75%; % age of tumor avβ3 overexpression, 21% and 25%. Three of 26 pts were progression-free at 8 weeks (2 at 500 mg; 1 at 2,000 mg dose). One pt at 2,000 mg had a prolonged partial response after initial 28% enlargement of target lesions. There were no grade 3 or 4 adverse events (AEs) except one pt with grade 3 lymphopenia at 2,000 mg. Although both doses of EMD 121974 were well tolerated, the 2,000 mg was associated with higher incidences of grade 2 fatigue, arthralgia, lymphopenia, peripheral neuropathy, and GI AEs. Optional tumor biopsies were performed on day 8, and the correlative studies to examine the molecular changes in the tumor are currently in progress. Conclusions: IV EMD 121974, 500 or 2,000 mg twice weekly, was well tolerated but had minimal clinical efficacy as a single-agent for MM. Supported by NCI grant N01 CM-17003 and CA16672 No significant financial relationships to disclose.

Front-line chemo-immunotherapy with carboplatin-paclitaxel using oregovomab indirect immunization in advanced ovarian cancer: A randomized phase II study

2020 ◽  
Vol 156 (3) ◽  
pp. 523-529 ◽  
Author(s):  
Molly Brewer ◽  
Roberto Angioli ◽  
Giovani Scambia ◽  
Domenica Lorusso ◽  
Corrado Terranova ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Advanced Ovarian Cancer ◽  
Front Line ◽  
Randomized Phase Ii
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