Panitumumab-based Maintenance in Patients With RAS Wild-type, Metastatic Colorectal Cancer (Valentino) (Valentino)
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ClinicalTrials.gov Identifier: NCT02476045 |
Recruitment Status : Unknown
Verified September 2016 by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano.
Recruitment status was: Recruiting
First Posted : June 19, 2015
Last Update Posted : September 14, 2016
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Tracking Information | |||
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First Submitted Date ICMJE | June 11, 2015 | ||
First Posted Date ICMJE | June 19, 2015 | ||
Last Update Posted Date | September 14, 2016 | ||
Study Start Date ICMJE | June 2015 | ||
Estimated Primary Completion Date | July 2018 (Final data collection date for primary outcome measure) | ||
Current Primary Outcome Measures ICMJE |
Efficacy [ Time Frame: 3 years ] in terms of progression free survival (from the enrollment)
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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 | Panitumumab-based Maintenance in Patients With RAS Wild-type, Metastatic Colorectal Cancer (Valentino) | ||
Official Title ICMJE | First-line FOLFOX-4 Plus Panitumumab Followed by 5-FU/LV Plus Panitumumab or Single-agent Panitumumab as Maintenance Therapy in Patients With RAS Wild-type, Metastatic Colorectal Cancer: the VALENTINO Study | ||
Brief Summary | Open label, randomized, multicenter, phase II study to compare the efficacy, in terms of non-inferiority of progression-free survival (PFS), of maintenance with panitumumab alone (arm B) as compared to panitumumab with 5-fluorouracil (5-FU) and leucovorin (LV) (arm A) following induction treatment with 5-fluorouracil + leucovorin+oxaliplatin (FOLFOX-4) and panitumumab in patients with RAS wild-type, metastatic colorectal cancer. The study involves an induction phase with panitumumab as 1 hour intravenous infusion at the dosage of 6 mg/kg, given every two weeks, plus FOLFOX-4 chemotherapy as standard guidelines. Before start of FOLFOX-4 plus panitumumab, at the time of enrollment, patients will be immediately randomized electronically 1:1 to one of the two maintenance arms. Induction treatment with FOLFOX-4 plus panitumumab will continue until progressive disease, unacceptable toxicity or informed consent withdrawal, or for up to 8 cycles. At the end of induction treatment, in presence of complete or partial response, or stable disease, non-progressing patients will be allocated to one of the two pre-assigned maintenance arms: A) 5-FU/LV (De Gramont regimen) plus panitumumab given at 6 mg/Kg every two weeks until progressive disease, unacceptable toxicity or informed consent withdrawal B) Panitumumab alone given at 6 mg/Kg every two weeks until progressive disease, unacceptable toxicity or informed consent withdrawal Imaging studies (thorax and abdominal CT or MRI scan) will be performed at baseline (4 weeks prior enrollment) and every 8 weeks (4 cycles) during treatment. |
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Detailed Description | First-line treatment of metastatic colorectal cancer should be administered according to the individual situation, patients' needs, therapeutic preconditions (e.g. neurotoxicity following adjuvant oxaliplatin-based chemotherapy), biomarkers and aggressiveness of the disease. The OPTIMOX1 trial showed an equivalent duration of disease control for a de-escalation / maintenance / reintroduction strategy compared with a treatment until progression strategy for oxaliplatin-based chemotherapy. Continuation of "lightened" fluoropyrimidine-based chemotherapy and bevacizumab represents a standard of care in the maintenance setting. Panitumumab with FOLFOX-4 chemotherapy represents a standard of care in the treatment of RAS wild-type metastatic colorectal cancer. The question whether the maintenance strategy might apply also to panitumumab in combination with chemotherapy is unknown at present. As the continuation of chemotherapy plus panitumumab until disease progression was foreseen in the hallmark "PRIME" trial, the question is whether a de-escalation of treatment intensity will not be inferior with respect to resulting time with tumor control, but allow patients a period with less toxicity and gain of quality of life. However, no data are available at present regarding the optimal maintenance treatment with anti-epidermal growth factor receptor (EGFR) monoclonal antibodies when used in association with first-line chemotherapy. This is an open label, randomized, multicenter, phase II study to compare the efficacy, in terms of non-inferiority of progression-free survival (PFS), of maintenance with panitumumab alone (arm B) as compared to panitumumab with 5-FU/LV (arm A) following induction treatment with FOLFOX-4 and panitumumab in patients with RAS wild-type, metastatic colorectal cancer. Secondary endpoints are:
Treatment involves an induction phase with panitumumab as 1 hour intravenous infusion at the dosage of 6 mg/kg, given every two weeks, plus FOLFOX-4 chemotherapy as standard guidelines. Before start of FOLFOX-4 plus panitumumab, at the time of enrollment, patients will be immediately randomized electronically 1:1 to one of the two maintenance arms. Induction treatment with FOLFOX-4 plus panitumumab will continue until progressive disease, unacceptable toxicity or informed consent withdrawal, or for up to 8 cycles. At the end of induction treatment, in presence of complete or partial response, or stable disease, non-progressing patients will be allocated to one of the two pre-assigned maintenance arms: A) 5-FU/LV (De Gramont regimen) plus panitumumab given at 6 mg/Kg every two weeks until progressive disease, unacceptable toxicity or informed consent withdrawal B) Panitumumab alone given at 6 mg/Kg every two weeks until progressive disease, unacceptable toxicity or informed consent withdrawal Imaging studies (thorax and abdominal CT or MRI scan) will be performed at baseline (4 weeks prior enrollment) and every 8 weeks (4 cycles) during treatment. The sample size is calculated on the basis of a non-inferiority hypothesis of median PFS with panitumumab alone as compared to 5-fluorouracil/leucovorin and panitumumab, taking into account a median PFS of 10 months observed in the PRIME trial. An overall sample size of 224 subjects (112 in the control group and 112 in the study group) achieves 90% power to detect a probability of 50% in the control group and a maximum difference of 15% in the study group, with a significance level of 0.1. The drop-out rate is 15%. The accrual pattern in the two groups is uniform (allocation 1:1). The study lasts for 24 months of enrollment and 12 months of follow-up |
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Study Type ICMJE | Interventional | ||
Study Phase ICMJE | Phase 2 | ||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE | Metastatic Colorectal 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 | Unknown status | ||
Estimated Enrollment ICMJE |
224 | ||
Original Estimated Enrollment ICMJE | Same as current | ||
Estimated Study Completion Date ICMJE | July 2018 | ||
Estimated Primary Completion Date | July 2018 (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 | Italy | ||
Removed Location Countries | |||
Administrative Information | |||
NCT Number ICMJE | NCT02476045 | ||
Other Study ID Numbers ICMJE | INT 70/15 | ||
Has Data Monitoring Committee | No | ||
U.S. FDA-regulated Product | Not Provided | ||
IPD Sharing Statement ICMJE | Not Provided | ||
Current Responsible Party | Fondazione IRCCS Istituto Nazionale dei Tumori, Milano | ||
Original Responsible Party | Same as current | ||
Current Study Sponsor ICMJE | Fondazione IRCCS Istituto Nazionale dei Tumori, Milano | ||
Original Study Sponsor ICMJE | Same as current | ||
Collaborators ICMJE | Not Provided | ||
Investigators ICMJE | Not Provided | ||
PRS Account | Fondazione IRCCS Istituto Nazionale dei Tumori, Milano | ||
Verification Date | September 2016 | ||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |