Phase II consolidation trial with anti-Lewis-Y monoclonal antibody (hu3S193) in platinum-sensitive ovarian cancer after a second remission

2021 ◽  
pp. ijgc-2020-002239
Author(s):  
Oren Smaletz ◽  
Gustavo Ismael ◽  
Maria Del Pilar Estevez-Diz ◽  
Ivana L O Nascimento ◽  
Ana Luiza Gomes de Morais ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Monoclonal Antibody ◽  
Epithelial Ovarian Cancer ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy ◽  
Lewis Y

ObjectiveTo investigate the efficacy and safety of hu3S193, a humanized anti-Lewis-Y monoclonal antibody, as a consolidation strategy in patients with platinum-sensitive recurrent epithelial ovarian cancer who achieved a second complete response after salvage platinum-doublet chemotherapy.MethodsThis single-arm phase II study accrued patients with recurrent epithelial ovarian cancer with Lewis-Y expression by immunohistochemistry who had achieved a second complete response after five to eight cycles of platinum-based chemotherapy. Patients received intravenous infusions of hu3S193, 30 mg/m2 every 2 weeks starting no more than 8 weeks after the last dose of chemotherapy and continuing for 12 doses, until disease progression, or unacceptable toxicity. The primary endpoint was progression-free survival of the second remission. Secondary objectives were safety and pharmacokinetics.ResultsTwenty-nine patients were enrolled. Most had a papillary/serous histology tumor (94%), stage III disease at diagnosis (75%), and five (17%) underwent secondary cytoreduction before salvage chemotherapy. Two patients were not eligible for efficacy but were considered for toxicity analysis. Eighteen patients (62%) completed the full consolidation treatment while nine patients progressed on treatment. At the time of analysis, 23 patients (85%) of the eligible population had progressed and seven of these patients (26%) had died. Median progression-free survival of the second remission was 12.1 months (95% CI: 10.6–13.9), with a 1-year progression-free survival of the second remission rate of 50.1%. The trial was terminated early since it was unlikely that the primary objective would be achieved. The most commonly reported treatment-related adverse events were nausea (55%) and vomiting (51%).ConclusionsHu3S193 did not show sufficient clinical activity as consolidation therapy in patients with recurrent epithelial ovarian cancer who achieved a second complete response after platinum-based chemotherapy.Trial registrationNCT01137071.

Panitumumab in platinum-sensitive epithelial ovarian cancer patients with KRAS wild-type: The PROVE-study, a phase II randomized multicenter study of the North-Eastern German Society of Gynaecologic Oncology.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5558-5558 ◽  
Author(s):  
Radoslav Chekerov ◽  
Peter Klare ◽  
Petra Krabisch ◽  
Jochem Potenberg ◽  
Georg Heinrich ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Ca 125 ◽  
Wild Type ◽  
Skin Reactions ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy

5558 Background: For ovarian cancer (OC) patients with platinum-sensitive recurrence the addition of new biologic agents to chemotherapy may improve survival. Panitumumab is a fully human monoclonal antibody specific to the epidermal growth factor receptor (EGFR). The purpose of this trial was to investigate the therapeutic efficacy of panitumumab in the combination with carboplatin-based chemotherapy in relation to the respective standard combination in patients with a KRAS wildtype with platinum-sensitive recurrent ovarian cancer (NCT01388621). Methods: Major eligibility criteria were pretreated platinum-sensitive epithelial ovarian/ fallopian/ peritoneal cancer and no more than 2 prior treatments for this disease. Only patients with measurable disease or elevated CA125 and with KRAS wild type were eligible. Patients were treated with Carboplatin AUC4/Gemcitabine 1000 mg/m² or Carboplatin AUC5/PLD 40 mg/m² and randomized to panitumumab 6 mg/kg day 1 and day 15, every 3 or 4 weeks. Tumor assessment was performed at baseline and at every third cycle according to CT-scan and CA-125 criteria. Results: In this multi-institutional phase II trial 102 patients were randomized and 96 enrolled for the final analysis. Progression-free survival in the intention-to-treat population (N=96) was 9.5 vs. 10.7 months (HR 0.829, 95%CI of 8.5-11.6 months vs 8.5-13.1 months) for the experimental vs. standard arm, p=0.45. Data of overall survival are not jet evaluable. The most common treatment related grade 3+ toxicities included hematologic toxicity (54%), skin reactions (18%) and gastrointestinal events (16%). Conclusions: The addition of panitumumab to platinum-based chemotherapy for recurrent ovarian cancer does not influence efficacy and progression-free survival in platinum sensitive patients, while no new additional toxicity aspects for panitumumab were evaluated. Clinical trial information: NCT01388621.

Phase III Trial of Observation Versus Six Courses of Paclitaxel in Patients With Advanced Epithelial Ovarian Cancer in Complete Response After Six Courses of Paclitaxel/Platinum-Based Chemotherapy: Final Results of the After-6 Protocol 1

2009 ◽  
Vol 27 (28) ◽  
pp. 4642-4648 ◽  
Author(s):  
Sergio Pecorelli ◽  
Giuseppe Favalli ◽  
Angiolo Gadducci ◽  
Dionyssios Katsaros ◽  
Pierluigi Benedetti Panici ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Complete Response ◽  
First Line ◽  
Free Survival ◽  
Consolidation Treatment ◽  
Platinum Based Chemotherapy ◽  
Advanced Epithelial Ovarian Cancer

Purpose To assess whether six courses of paclitaxel are effective as consolidation treatment in patients with advanced epithelial ovarian cancer who are in complete response after first-line paclitaxel/platinum–based chemotherapy. Patients and Methods Patients with stages IIb to IV disease in clinical or pathologic complete response after six courses of paclitaxel/platinum–based chemotherapy were randomly allocated to either observation (ie, control) or six courses of paclitaxel 175 mg/m2 every 3 weeks (ie, maintenance). Results Two hundred patients were randomly assigned from March 1999 to July 2006. Because of the low accrual rate, an unplanned interim analysis of futility according to the Bayesian approach was performed. Grade 2 or greater motor neurotoxicity and sensory neurotoxicity were reported in 11.3% and 28.0% of the paclitaxel-arm patients, respectively. After a median follow-up of 43.5 months, 107 patients (53%) had experienced relapse, and 48 patients (24%) had died. Two-year progression-free survival rates were 54% (95% CI, 43% to 64%) and 59% (95% CI, 49% to 69%; P = not significant) in the control and maintenance arms, respectively. Corresponding 2-year overall survival rates were 90% (95% CI, 84% to 97%) and 87% (95% CI, 80% to 94%; P = not significant), respectively. The Cox model showed that residual disease after initial surgery (macroscopic v no macroscopic residuum; hazard ratio [HR], 1.91; 95%CI, 1.21 to 3.03) and stage (IIIc to IV v others; HR, 3.10; 95% CI, 1.13 to 8.48) were independent prognostic factors for progression-free survival, whereas the treatment arm (maintenance v control) had no prognostic relevance. Conclusion A consolidation treatment with six cycles of paclitaxel does not prolong progression-free survival or overall survival in patients in complete response after first-line paclitaxel/platinum–based regimens.

Cytoreductive surgery followed by chemotherapy and olaparib maintenance in BRCA 1/2 mutated recurrent ovarian cancer: a retrospective MITO group study

2021 ◽  
pp. ijgc-2020-002343
Author(s):  
Sabrina Chiara Cecere ◽  
Lucia Musacchio ◽  
Michele Bartoletti ◽  
Vanda Salutari ◽  
Laura Arenare ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Cytoreductive Surgery ◽  
Response Rate ◽  
Progression Free Survival ◽  
Recurrent Ovarian Cancer ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Free Interval ◽  
Platinum Based Chemotherapy

IntroductionThe role of cytoreductive surgery in the poly-ADP ribose polymerase inhibitors era is not fully investigated. We evaluated the impact of surgery performed prior to platinum-based chemotherapy followed by olaparib maintenance in platinum-sensitive BRCA-mutated recurrent ovarian cancer.MethodsThis retrospective study included platinum-sensitive recurrent ovarian cancer BRCA-mutated patients from 13 Multicenter Italian Trials in Ovarian cancer and gynecological malignancies centers treated between September 2015 and May 2019. The primary outcomes were progression-free survival and overall survival. Data on post-progression treatment was also assessed.ResultsAmong 209 patients, 72 patients (34.5%) underwent cytoreductive surgery followed by platinum-based chemotherapy and olaparib maintenance, while 137 patients (65.5%) underwent chemotherapy treatment alone. After a median follow-up of 37.3 months (95% CI: 33.4 to 40.8), median progression-free survival in the surgery group was not reached, compared with 11 months in patients receiving chemotherapy alone (P<0.001). Median overall survival was nearly double in patients undergoing surgery before chemotherapy (55 vs 28 months, P<0.001). Post-progression therapy was assessed in 127 patients: response rate to chemotherapy was 29.2%, 8.8%, and 9.0% in patients with platinum-free interval >12 months, between 6 and 12 months, and <6 months, respectively.ConclusionCytoreductive surgery performed before platinum therapy and olaparib maintenance was associated with longer progression-free survival and overall survival in BRCA-mutated platinum-sensitive relapsed ovarian cancer patients. In accordance with our preliminary results, the response rate to chemotherapy given after progression during olaparib was associated with platinum-free interval.

Cambridge Translational Cancer Research Ovarian Study 01 (CTCR-OV01): Expression profiling of advanced epithelial ovarian cancer (EOC) to predict chemotherapy response. A randomised phase II trial design with prospective translational endpoints

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15018-15018
Author(s):  
H. M. Earl ◽  
A. Ahmed ◽  
A. Vallier ◽  
H. Hatcher ◽  
C. A. Parkinson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Phase Ii ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Chemotherapy Response ◽  
Severe Toxicity ◽  
Debulking Surgery ◽  
Fresh Tissue ◽  
Free Survival

15018 Methods: CTCR-OV01 is a randomised phase II neoadjuvant study in stage III-IV epithelial ovarian cancer (EOC). Patients (pts) were consented for diagnostic and fresh tissue research biopsies, and after diagnosis was confirmed, were randomised (1:1) to: Arm A: Carboplatin AUC 7 every 3 weeks (C) × 3 cycles (cy); then interval debulking surgery (IDS); then C AUC 6 with paclitaxel 175 mg/m2 q 3w (CT) × 3 cy; and finally paclitaxel 175 mg/m2 q 3w (T) × 3 cy. Arm B: T × 3 cy; IDS; CT × 3 cy; C × 3 cy. At IDS further fresh tissue samples were collected. Clinical Endpoints: (i) Partial response rate after three cycles of chemotherapy based on CA125 (CA125 RR) and CT scan (CT RR). (ii) Median progression-free survival (PFS). Translational endpoints: Candidate genes and molecular profiles as predictive markers of response/resistance to C and T. Results: Jan ‘02-Dec ‘04, 48 pts were randomised in a single centre study. 4 patients were excluded from analysis (3pts severe toxicity; 1pt incorrect histopathology), leaving 44 patients (21pts A/23 pts B). Median age 60 yr (range 36–75 yrs); 42/44 serous papillary histology; stage III/IV = 77%/23%; grade I/II/III = 2%/34%/64%. All prognostic factors were well balanced between treatment arms. Median follow-up is 22 months (IQR 17–33.5). CA125 RR to pre-operative chemotherapy was A/B = 65%/60% (p = 1). CT RR was A/B = 47%/35% (p = 0.15). CA125 RR, was significantly associated with improvement in progression-free survival (PFS) compared to non-responders (17.3 v 12.4 months; log rank test p = 0.027). Optimal debulking surgery was possible in A/B = 53%/63%. Median PFS was 14 months (m) (A/B = 13 m/14 m (p = 0.53)). Supervised analysis of Affymetrix expression data showed significant enrichment for differential extracellular gene expression in paclitaxel resistant patients. Conclusions: Prospective controlled randomized trials using neoadjuvant treatment are ideally suited for translational research in EOC and provide unique sample sets molecular analysis. No significant financial relationships to disclose.

Genetic polymorphisms in hMSH2 and hMLH1 genes are associated with prognosis in epithelial ovarian cancer patients

2019 ◽  
Vol 29 (7) ◽  
pp. 1148-1155 ◽  
Author(s):  
Wengang Si ◽  
Shan Kang ◽  
Haiyan Sun ◽  
Juan Chen ◽  
Shiru Cao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cancer Patients ◽  
Genetic Polymorphisms ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Allele Frequencies ◽  
Free Survival ◽  
Platinum Based Chemotherapy

ObjectiveDNA mismatch repair deficiency is not only thought to promote tumorigenesis but is also suggested to be associated with platinum-based chemotherapy treatment. In this study, we investigated the effects of two genetic polymorphisms in the hMSH2 and hMLH1 genes on the risk of epithelial ovarian cancer and the clinical outcome of patients treated with platinum-based chemotherapy.MethodsA case-control study was performed in 536 epithelial ovarian cancer patients and 532 control women. Genotypes of two polymorphisms were determined by the polymerase chain reaction/ligase detection reaction method. Pearson Chi-square test was used to evaluate genotype distributions and allele frequencies in the patients and controls. Kaplan-Meier survival curves, and univariate and multivariate Cox regression models were used to analyze the effect of polymorphisms on patients’ prognoses.ResultsThe genotype and allele frequencies of the rs2303428 and rs1800734 polymorphisms were not significantly different between the case and control groups. Compared with wild homozygous genotype, the presence of variant alleles (heterozygous and variant homozygous genotypes) did not affect the risk of developing epithelial ovarian cancer. However, survival analysis showed that the rs2303428 polymorphism was related to the prognosis of epithelial ovarian cancer patients. Compared with the TT genotype, patients carrying the C allele had a shorter progression-free survival during the 3- and 5-year follow-up (HR 1.41, 95% CI 1.07 to 1.87 and HR 1.56, 95% CI 1.12 to 2.16, respectively). For the rs1800734 polymorphism, the A allele may significantly increase patients’ progression-free survival compared with the GG genotype in the 5-year follow-up (HR 0.66, 95% CI 0.44 to 0.98).ConclusionOur research suggests that genetic polymorphisms in hMSH2 and hMLH1 may indicate the clinical progression of epithelial ovarian cancer patients treated with platinum-based chemotherapy.

Đánh giá kết quả điều trị bệnh nhân ung thư biểu mô buồng trứng tái phát bằng phác đồ paclitaxel tại Bệnh viện K

2021 ◽  
Author(s):  
Thi Lan Nguyen
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Sensory Nerve ◽  
Progression Free Survival ◽  
Complete Response ◽  
Recurrent Ovarian Cancer ◽  
Initial Therapy ◽  
Ca 125 ◽  
Free Survival ◽  
Platinum Resistant

TÓM TẮT Đặt vấn đề: Ung thư biểu mô buồng trứng (UTBMBT) là bệnh ác tính của tế bào biểu mô buồng trứng. Bệnh có tiên lượng xấu. Mặc dù điều trị ban đầu tối ưu, UTBMBT sẽ tái phát và cần được điều trị. Điều trị UTBMBT tái phát còn gặp nhiều khó khăn. Nghiên cứu này nhằm đánh giá một số đặc điểm lâm sàng, cận lâm sàng UTBMBT tái phát kháng platinum và kết quả điều trị phác đồ paclitaxel nhóm bệnh nhân này. Phương pháp nghiên cứu: Chúng tôi đưa vào nghiên cứu 65 bệnh nhân được điều trị phác đồ paclitaxel cho ung thư biểu mô buồng trứng tái phát khángplatinum, thỏa mãn các tiêu chuẩn lựa chọn và tiêu chuẩn loại trừ. Với phương pháp nghiên cứu mô tả cắt ngang. Kết quả: Các vị trí tái phát thường gặp nhất là hạch (54,3%), phúc mạc (50%), gan (23,9%). Tăng CA125 ở thời điểm tái phát (77,8%) tỷ lệ đáp ứng chung là 22,5%. Tỷ lệ kiểm soát bệnh (bao gồm đáp ứng hoàn toàn, đáp ứng một phần và bệnh giữ nguyên) đạt 62,5%. Trung vị thời gian sống thêm không tiến triển 26,1 tuần (CI 95%: 20,9 - 28,4). Độc tính trên hệ tạo huyết là giảm bạch cầu đa nhân trung tính độ 1,2. Độc tính trên gan 9,3% chủ yếu tăng men gan độ 1,2. Không có độc tính trên thận. Các tác dụng không mong muốn khác như rụng tóc độ 2: 2,7%, viêm miệng gặp ở 2,1% bệnh nhân, thần kinh cảm giác 15%, chỉ gặp ở độ 1. Có mối liên quan giữa đáp ứng điều trị và nồng độ CA 125. Kết luận: Phác đồ paclitaxel sử dụng điều trị UTBMBT tái phát kháng platinum là phác đồ phù hợp về tính hiệu quả và an toàn cho các bệnh nhân UTBMBT đã trải qua phác đồ hóa trị trước đó. ABSTRACT OUTCOMES OFRECURRENT EPITHELIAL OVARIAN CANCER PATIENTS TREATED WITH PACLITAXEL REGIMEN AT K HOSPITAL Introduction: Epithelial ovarian cancer is a malignant abnormality of the epithelial cell of the ovary. The disease has a poor prognosis. Despite optimal initial therapy, the majority of patients will relapse and require further treatment. Treatment of recurrent ovarian cancer is still challenging. This study aims to describe clinical and subclinical characteristics of patients with platinum - resistant relapsed ovarian carcinoma and evaluate the treatment results of the paclitaxel regimen on these patients. Methods: We enrolled 65 patients with platinum - resistant recurrent epithelial ovarian cancer treated with paclitaxel regimen, met the inclusion and exclusion criteria. Results: The most common recurrent sites were lymph nodes (54.3%), peritoneum (50%), and liver (23.9%). CA125 increased at the time of recurrence (77.8%), the overall response rate was 22.5%. Disease control rates (including complete response, partial response, and stable disease) were achieved at 62.5%. Median progression - free survival was 26.1 weeks (95% CI: 20.9 - 28.4). Hematopoietic system toxicities include neutropenia of grade 1, 2. Hepatotoxicity occupied 9.3%, mainly liver enzymes elevation of grade 1, 2. No renal toxicity was observed. Other undesirable effects include hair loss of grade 2 (2.7%), stomatitis(2.1%), sensory nerve 15% but only grade 1. There was a relationship between treatment response and CA 125 levels. Conclusion: The paclitaxel regimen used to treat platinum - resistant recurrent epithelial ovarian cancer is the appropriate regimen in terms of efficacy and safety. After several lines of chemotherapy regimens. Keywords: Recurrent epithelial ovarian cancer, platinum - resistant, paclitaxel.

Olaparib maintenance monotherapy in platinum-sensitive, relapsed ovarian cancer without germline BRCA mutations: OPINION Phase IIIb study design

2019 ◽  
Vol 15 (32) ◽  
pp. 3651-3663
Author(s):  
Andres M Poveda ◽  
Richard Davidson ◽  
Christopher Blakeley ◽  
Alvin Milner
Keyword(s):  
Ovarian Cancer ◽  
Brca2 Mutation ◽  
Progression Free Survival ◽  
Open Label ◽  
Brca Mutations ◽  
Clinical Trial Registration ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Platinum Based Chemotherapy ◽  
Phase Iiib

The poly(ADP-ribose) polymerase inhibitor olaparib (Lynparza™) is approved for maintenance treatment of platinum-sensitive relapsed ovarian cancer. OPINION is a single-arm, open-label, multicenter, Phase IIIb study to assess the efficacy and safety of olaparib tablet maintenance therapy in women with high-grade serous or endometrioid platinum-sensitive relapsed ovarian cancer without a germline BRCA1 or BRCA2 mutation. Eligible patients should have received ≥2 prior lines of platinum-based chemotherapy and be in complete or partial response following their most recent course or have no evidence of disease. Patients will receive olaparib tablets (300 mg twice daily) until disease progression, unacceptable toxicity or another discontinuation criterion. The primary end point is investigator-assessed progression-free survival; secondary end points include progression-free survival according to tumor homologous recombination deficiency status. Clinical trial registration: NCT03402841.

An open label, randomized, parallel, phase II trial to evaluate the efficacy and safety of cremophor-free, polymeric micelle formulation of paclitaxel compared to paclitaxel in subjects with ovarian cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 5568-5568
Author(s):  
Yong-Man Kim ◽  
Shin-Wha Lee ◽  
Chi Heum Cho ◽  
Soo-Young Hur ◽  
Byoung-Gie Kim ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Polymeric Micelle ◽  
Ca 125 ◽  
Free Survival ◽  
Composite Response

5568 Background: Cremorphor EL, used to enhance drug solubility, may add to paclitaxel’s toxicities such as hypersensitivity reactions or peripheral neuropathy. This multi-institutional phase II trial is to evaluate the efficacy and safety of Cremophor-Free, Polymeric Micelle Formulation of Paclitaxel (Genexol-PM) compared to Paclitaxel (Genexol) as a combined chemotherapy with carboplatin in patients with advanced epithelial ovarian cancer. Methods: In this phase II, randomized, parallel study, patients with FIGO stage IC-IV epithelial ovarian cancer after debulking surgery received intravenously Genexol-PM 260 mg/m2 or Genexol 175 mg/m2 combined with carboplatin iv (AUC 5) on day 1 of every 3-week cycle for a maximum of six cycles. The primary endpoint was composite response by GCIG CA-125 Response and Response Evaluation Criteria In Solid Tumors (RECIST). Secondary and exploratory endpoints included overall survival, progression-free survival, time to tumor progression, and safety and tolerability. Results: A total of 102 patients were randomized to Genexol-PM plus carboplatin (n = 51) or Genexol plus carboplatin (n = 51). Composite response rate in patients with or without measurable disease was 88.0% in the Genexol-PM plus carboplatin group and 77.1% in the Genexol plus carboplatin group. Noninferiority of Genexol-PM plus carboplatin compared with Genexol plus carboplatin was confirmed for composite response rate by CA-125/RECIST criteria. There were no differences in progression-free survival and overall tumor progression between the groups. Although there was a higher rate of grade 3 neutropenia in the Genexol-PM plus carboplatin group, the overall rate of hemodynamic adverse events was comparable between the 2 groups. There was no difference in peripheral neuropathy and hypersensitivity. No unexpected safety concerns were identified in this study. Conclusions: High-dose of Genexol-PM in combination with carboplatin was well tolerated, and its response rate was noninferior to that of Genexol plus carboplatin in patients with advanced epithelial ovarian cancer. Clinical trial information: NCT01276548.

scholarly journals ICON 9—an international phase III randomized study to evaluate the efficacy of maintenance therapy with olaparib and cediranib or olaparib alone in patients with relapsed platinum-sensitive ovarian cancer following a response to platinum-based chemotherapy

2020 ◽  
Vol 31 (1) ◽  
pp. 134-138
Author(s):  
Osnat Elyashiv ◽  
Jonathan Ledermann ◽  
Gita Parmar ◽  
Laura Farrelly ◽  
Nicholas Counsell ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Maintenance Therapy ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Wild Type ◽  
Free Survival ◽  
Platinum Sensitive ◽  
Primary Endpoints ◽  
Platinum Based Chemotherapy

BackgroundTwo novel biological agents—cediranib targeting angiogenesis, and olaparib targeting DNA repair processes—have individually led to an improvement in ovarian cancer control. The aim of ICON9 is to investigate the combination of cediranib and olaparib maintenance in recurrent ovarian cancer following platinum-based therapy.Primary objectiveTo assess the efficacy of maintenance treatment with olaparib in combination with cediranib compared with olaparib alone following a response to platinum-based chemotherapy in women with platinum-sensitive ovarian, fallopian tube or peritoneal cancer during first relapse.Study hypothesisMaintenance therapy with cediranib and olaparib in combination is associated with improved patient outcomes compared with olaparib alone.Trial designInternational phase III randomized controlled trial. Following a response to platinum-based chemotherapy patients are randomized 1:1 to either oral olaparib and cediranib (intervention arm) or oral olaparib alone (control arm).Major inclusion criteriaPatients with a known diagnosis of high grade serous or endometrioid carcinoma of the ovary, fallopian tube or peritoneum, progressing more than 6 months after first-line platinum-based chemotherapy, who have responded to second-line platinum-based chemotherapy.Primary endpointsProgression-free and overall survival. Co-primary endpoints to be assessed using a fixed-sequence gatekeeping approach: (1) progression-free survival, all patients; (2) progression-free survival, BRCA wild type; (3) overall survival, all patients; (4) overall survival, BRCA wild type.Sample size618 patients will be recruited.Estimated dates for completing accrual and presenting resultsAccrual is expected to be completed in 2024 with presentation of results in 2025.Trial registrationClinicalTrials.gov: NCT03278717.

Sign in / Sign up

Export Citation Format

Share Document