Efficacy and Safety Study of Sorafenib With Topotecan in Patients With Platinum-resistant Recurrent Ovarian Cancer (TRIAS 2009)
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ClinicalTrials.gov Identifier: NCT01047891 |
Recruitment Status :
Completed
First Posted : January 13, 2010
Last Update Posted : February 18, 2015
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Tracking Information | ||||
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First Submitted Date ICMJE | January 12, 2010 | |||
First Posted Date ICMJE | January 13, 2010 | |||
Last Update Posted Date | February 18, 2015 | |||
Study Start Date ICMJE | January 2010 | |||
Actual Primary Completion Date | February 2015 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
Primary objective: Determination of the progression-free survival (PFS) of patients treated with topotecan and sorafenib versus topotecan and placebo [ Time Frame: 18 months ] The primary target value of this study is the comparison of the median progression-free survival time between the two study arms. Progression-free survival time (PFS) of a patient is defined as the time in months from start of the first therapy cycle until PD or death is observed
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Original Primary Outcome Measures ICMJE |
Primary objective: Determination of the progression-free survival (PFS) of patients treated with topotecan and sorafenib versus topotecan and placebo [ Time Frame: 18 months ] | |||
Change History | ||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
Secondary objectives: Overall survival, Response rate, Duration of response, Time to progression (TTP, Safety and tolerability, Assessment of quality of life over time as defined by EORTC-QLQ C 30 and Ovar 28 questionnaire and, in case of participation [ Time Frame: 18 months ] | |||
Current Other Pre-specified Outcome Measures | Not Provided | |||
Original Other Pre-specified Outcome Measures | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | Efficacy and Safety Study of Sorafenib With Topotecan in Patients With Platinum-resistant Recurrent Ovarian Cancer | |||
Official Title ICMJE | A Randomized, Double-blind, Placebo Controlled, Multicenter Phase II Study to Assess the Efficacy and Safety of Sorafenib Added to Standard Treatment With Topotecan in Patients With Platinum-resistant Recurrent Ovarian Cancer | |||
Brief Summary | It is assumed, that the patients of the standard arm show a median progression-free survival time of 4.4 months those of the experimental arm of at least 6.9 months. Assuming a recruitment period of 18 months and follow-up for at least 12 months a total sample size of 174 patients is required (two-sided, α=0.05, 80% power). To account for 5% drop-outs 184 patients will be randomized. A Data Monitoring and Safety Board (DMSB) will be established. This board will evaluate the safety profile of the drug combination after 6 patients and after 12 patients have received 1 cycle of treatment. |
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Detailed Description | Ovarian cancer continues to be a leading cause of cancer-related deaths in women and is the leading cause of deaths attributed to gynecologic malignancies. Because ovarian cancer is usually asymptomatic in its early stages, the disease often has spread outside of the pelvic region at the time of diagnosis and requires debulking surgery followed by systemic chemotherapy. First-line chemotherapy involves platinum-based treatments, including the widely adopted regimens of cisplatin/paclitaxel, carboplatin/paclitaxel, and single-agent carboplatin. Although these regimens yield relatively satisfactory tumor response rates, the majority of patients experience disease recurrence and receive additional treatments. For such patients, a number of antitumor agents with novel mechanisms of action (topotecan, gemcitabine, pegylated liposomal doxorubicin, docetaxel, etoposide) have been applied, in addition to retreatment with platinum, with the goal of re-establishing remission or disease control, minimizing disease-related symptoms, improving quality of life, and extending patient survival. Of these agents, topotecan (Hycamtin®; GlaxoSmithKline) is one of the best-characterized agents in the recurrent setting. Topotecan is an S-phase 1-dependent cytotoxic agent that targets the topoisomerase I enzyme and exhibits broad activity in solid tumors and is approved for the treatment of recurrent ovarian cancer in US and in most western countries. Data from preclinical and clinical studies reported in the last 2 years demonstrate the importance of several proangiogenic factors in the tumorigenesis and prognosis of ovarian cancer, suggesting possible new targets for antiangiogenic therapy. Once-daily oral treatment with Sorafenib produces broad spectrum antitumor efficacy in preclinical tumor models including also xenograft models of ovarian carcinoma. Preliminary antitumor activity has been reported in single ovarian cancer patients in several phase I and phase II studies. Most promising strategy in the therapy of advanced and recurrent ovarian cancer seems to be the combination of cytotoxic agents and targeted therapies. Furthermore an oral therapy to achieve and maintain long term tumor control seems to be very attractive. Therefore Sorafenib and Topotecan would make a rational therapeutic strategy for combination in recurrent ovarian cancer. |
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Study Type ICMJE | Interventional | |||
Study Phase ICMJE | Phase 2 | |||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Treatment |
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Condition ICMJE | Ovarian Cancer | |||
Intervention ICMJE | Drug: Sorafenib
Topotecan 1,25 mg/m²/d administered as an i.v. infusion over 30 minutes once daily on days 1-5, every 21 days and Sorafenib 400 mg orally twice daily (total daily dose 800 mg) administered
Other Name: Nexavar®
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Study Arms ICMJE | Experimental: Experimental
Intervention: Drug: Sorafenib
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Publications * | Chekerov R, Hilpert F, Mahner S, El-Balat A, Harter P, De Gregorio N, Fridrich C, Markmann S, Potenberg J, Lorenz R, Oskay-Oezcelik G, Schmidt M, Krabisch P, Lueck HJ, Richter R, Braicu EI, du Bois A, Sehouli J; NOGGO; AGO TRIAS Investigators. Sorafenib plus topotecan versus placebo plus topotecan for platinum-resistant ovarian cancer (TRIAS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2018 Sep;19(9):1247-1258. doi: 10.1016/S1470-2045(18)30372-3. Epub 2018 Aug 9. | |||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | ||||
Recruitment Status ICMJE | Completed | |||
Actual Enrollment ICMJE |
174 | |||
Original Estimated Enrollment ICMJE |
184 | |||
Actual Study Completion Date ICMJE | February 2015 | |||
Actual Primary Completion Date | February 2015 (Final data collection date for primary outcome measure) | |||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years and older (Adult, Older Adult) | |||
Accepts Healthy Volunteers ICMJE | No | |||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | |||
Listed Location Countries ICMJE | Germany | |||
Removed Location Countries | ||||
Administrative Information | ||||
NCT Number ICMJE | NCT01047891 | |||
Other Study ID Numbers ICMJE | TRIAS 2009 | |||
Has Data Monitoring Committee | Yes | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement ICMJE | Not Provided | |||
Current Responsible Party | JSehouli, Charite University, Berlin, Germany | |||
Original Responsible Party | Represented by Prof. Dr. med. Jalid Sehouli, Charité - Universitätsmedizin Berlin | |||
Current Study Sponsor ICMJE | JSehouli | |||
Original Study Sponsor ICMJE | Charite University, Berlin, Germany | |||
Collaborators ICMJE | Not Provided | |||
Investigators ICMJE |
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PRS Account | Charite University, Berlin, Germany | |||
Verification Date | February 2015 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |