Cisplatin and 5-FU +/- Panitumumab for Patients With Nonresectable,Advanced or Metastatic Esophageal Squamous Cell Cancer (POWER)
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ClinicalTrials.gov Identifier: NCT01627379 |
Recruitment Status :
Terminated
(Sponsor decision due to recommendation of the IDMC.)
First Posted : June 25, 2012
Last Update Posted : March 2, 2018
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Tracking Information | ||||
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First Submitted Date ICMJE | June 13, 2012 | |||
First Posted Date ICMJE | June 25, 2012 | |||
Last Update Posted Date | March 2, 2018 | |||
Study Start Date ICMJE | May 2012 | |||
Actual Primary Completion Date | May 2015 (Final data collection date for primary outcome measure) | |||
Current Primary Outcome Measures ICMJE |
Overall Survival [ Time Frame: 3 years ] Kaplan-Meier estimate of the median time between date of randomization and the date of death from any cause or the date of last follow-up in case of no documentation of death.
Comparison of Overall survival of treatment arms "Panitumumab + Chemotherapy" and "Chemotherapy only" in patients with nonresectable, advanced or metastatic ESCC.
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Original Primary Outcome Measures ICMJE | Same as current | |||
Change History | ||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | |||
Current Other Pre-specified Outcome Measures | Not Provided | |||
Original Other Pre-specified Outcome Measures | Not Provided | |||
Descriptive Information | ||||
Brief Title ICMJE | Cisplatin and 5-FU +/- Panitumumab for Patients With Nonresectable,Advanced or Metastatic Esophageal Squamous Cell Cancer | |||
Official Title ICMJE | An Open-label, Randomized Phase III Trial of Cisplatin and 5-fluorouracil With or Without Panitumumab for Patients With Nonresectable, Advanced or Metastatic Esophageal Squamous Cell Cancer | |||
Brief Summary | More than 50% of patients with esophageal cancer have locally advanced or metastatic disease at presentation. The use of chemotherapy for this patient group is increasing with the intention of local and distant tumor control, improving quality of life and prolongation of survival. Previous data suggested not only that EGFR antibody targeted therapy may be safely combined with cisplatin and 5-FU but also may increase the efficacy of standard cisplatin / 5-FU regime. In the present study, patients with nonresectable, advanced or metastatic esophageal squamous cell cancer (ESCC) will receive chemotherapy or chemotherapy plus panitumumab every 3 weeks until disease progression occurs. The primary objective is to demonstrate superiority of 5-FU, Cisplatin and Panitumumab over 5-FU and Cisplatin alone in terms of overall survival in esophageal cancer. |
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Detailed Description | More than 50% of patients with esophageal cancer have locally advanced or metastatic disease at presentation. The use of chemotherapy for this patient group is increasing with the intention of local and distant tumor control, improving quality of life and prolongation of survival. The most frequently used agents are 5-fluorouracil, cisplatin, with or without various anthracyclines. Cisplatin plus continuous 5-fluorouracil are the standard of care regimens. Taxanes and anthracyclins are eligible agents for possible future studies, however with higher incidences of toxicities and life threatening complications. Response rates for single agents range from 15%-30%. Combination regimens usually tend to produce higher response rates and occasionally patients achieve complete responses (0%-11%). However, with the combination regimens, the median survival time remains clearly less than 10 months, mostly between 4-8 months [Homs MY et al]. In comparison of different chemotherapy protocols, there was no consistent benefit of any specific chemotherapy regimen. So far, cisplatin combined with 5-fluorouracil is one of the approved standard regimens in esophageal cancer world wide[Medical Research Council Oesophageal Cancer Group]. This so called three-weekly MRC regimen has a better toxicity profile than the four weekly CF regimen given in Central Europe with the higher Cisplatin dose[Lorenzen S et al], but less overall chemotherapy given per 4 months. Advances in molecular biology and new molecular technologies can possibly contribute to improvement of response to neoadjuvant or palliative therapy in ESCC patients as well. EGFR1 blockade with platinum-based chemotherapy already significantly improved response rates as well as the progression-free and overall survival compared to chemotherapy alone in patients with head and neck tumors, which are also squamous cancers[Vermorken JB et al]. Even more, the Arbeitsgemeinschaft Internistische Onkologie (AIO) has performed a randomized phase II study of the EGFR antibody cetuximab plus cisplatin/5-fluorouracil versus cisplatin/5-fluorouracil alone in first-line metastatic ESCC[Lorenzen S et al]. For a maximum of six 28-day cycles, patients received cisplatin 100 mg/m(2), day 1, plus 5-FU 1000 mg/m(2) days 1-5 (CF), either alone or in combination with cetuximab (CET-CF). The primary endpoint was tumor response. From 62 eligible patients included, 32 receiving CET-CF and 30 CF. Cetuximab weekly did not exacerbate grade 3/4 toxicity, except for rash (6% vs 0%) and diarrhea (16% vs 0%). The overall response rate according to RECIST criteria were 19% and 13% and the disease control rates, were 75% and 57% for the CET-CF and CF arms, respectively. With a median follow-up of 21.5 months, the median progression-free survival was 5.9 and 3.6 months and median overall survival 9.5 and 5.5 months for CET-CF and CF, respectively. No KRAS codon 12/13 tumor mutations were identified in the 37 evaluated samples. Thus, with respect to the AIO data and in concordance with the head and neck data by Vermorken, EGFR antibody targeted therapy may not only be safely combined with CF, but may also very likely increase the efficacy of standard CF, particularly with regard to a chosen primary endpoint of overall survival. Therefore, the aim of this study is to investigate if the overall survival of patients with squamous cell carcinoma of the esophagus can be prolonged if panitumumab is added to the standard CF chemotherapy. |
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Study Type ICMJE | Interventional | |||
Study Phase ICMJE | Phase 3 | |||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Esophageal Squamous Cell Cancer | |||
Intervention ICMJE |
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Study Arms ICMJE |
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Publications * |
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* 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 | Terminated | |||
Estimated Enrollment ICMJE |
300 | |||
Original Estimated Enrollment ICMJE | Same as current | |||
Actual Study Completion Date ICMJE | May 2017 | |||
Actual Primary Completion Date | May 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 | NCT01627379 | |||
Other Study ID Numbers ICMJE | POWER / AIO-STO-0309 2010-020606-15 ( EudraCT Number ) |
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Has Data Monitoring Committee | Yes | |||
U.S. FDA-regulated Product | Not Provided | |||
IPD Sharing Statement ICMJE | Not Provided | |||
Current Responsible Party | AIO-Studien-gGmbH | |||
Original Responsible Party | Same as current | |||
Current Study Sponsor ICMJE | AIO-Studien-gGmbH | |||
Original Study Sponsor ICMJE | Same as current | |||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | AIO-Studien-gGmbH | |||
Verification Date | March 2018 | |||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |