Chemoradiation With Gemcitabine in Combination With Panitumumab for Patients With Locally Advanced Pancreatic Cancer (Vectibix)
The purpose of this study is to investigate whether the addition of panitumumab to radiotherapy plus gemcitabine will increase the number of patients who are alive and progression free at 7 months.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Chemoradiation With Gemcitabine in Combination With Panitumumab for Patients With Locally Advanced Pancreatic Cancer|
- Phase I: the recommended safe dosing for the combination of chemoradiation with gemcitabine plus panitumumab. [ Time Frame: 43 days ] [ Designated as safety issue: Yes ]During the phase I part of the study, we have planned to study four dose levels of panitumumab if no MTD is being derived before the final dose level. Patients will be enrolled in cohorts of 3 per dose level. If there are no dose-limiting toxicities (DLTs) experienced by the first 3 patients in a cohort during the first 43 days after the first study treatment, additional patients will be entered in the next dose level. At the final dose level recommended for the phase II study a minimum of 6 patients will be treated.
- Phase II: the proportion of patients that is alive and progression-free at 7 months. [ Time Frame: 1 year ] [ Designated as safety issue: No ]For each patient, the time of progression will be recorded. Any patient who discontinues treatment due to adverse reactions, refusal, or who goes on to receive alternate therapy will be considered censored at their last tumor assessment. The sample size was determined based upon a Bryant Day Phase II clinical trial design, taking into account both activity as well as toxicity. The proportion of patients with 7 month PFS will be calculated with exact 95% confidence intervals.
- Phase II: safety and tolerability [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]Toxicities will be tabulated and summarized overall and across grade and type according to CTC criteria. When grade ≥3 toxicity occurs in ≥ 50% of patients this will be evaluated as unacceptable toxicity according to the two step evaluation design as described. This relatively high percentage of toxicity is based on the details of multiple studies of combination chemoradiation with gemcitabine as given in the introduction.
- Early signs of clinical activity of the combination of chemoradiation with gemcitabine plus panitumumab. [ Time Frame: 1 year ] [ Designated as safety issue: No ]The assessment of early signs of clinical activity will be determined based upon CT-scan evaluation, pain relieve and decay in CA19.9 (where applicable).
- Clinical response rate of the combination of chemoradiation with gemcitabine plus panitumumab. [ Time Frame: 1 year ] [ Designated as safety issue: No ]The response rate will be determined as the proportion of treated patients who had a partial or complete response (as defined in Response Criteria section).
- Time-to-progression (TTP) and overall survival [ Time Frame: 1 year ] [ Designated as safety issue: No ]TTP and overall survival will be described in all patients using Kaplan-Meier curves. TTP will be defined based on CT-scan imaging based on Response Criteria according to RECIST (version 1.1) preferably or based on clinical evaluation and will be measured from enrolment. In addition, analyses of TTP will include death as being progressive disease. Kaplan-Meier curves will be used to summarize the pattern of TTP and overall survival. M median TTP and overall survival will be calculated along with 95% confidence intervals.
|Study Start Date:||July 2010|
|Estimated Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
During the first 6 weeks Panitumumab will be administered weekly in combination with radiotherapy plus gemcitabine. From week 8 and further gemcitabine will be administered as monotherapy until disease progression or unacceptable toxicity, for a maximum duration of 1 year.
This is a phase I/II, multi-center dose escalation study.
Patients will be enrolled in cohorts of 3 per dose level until the MTD of panitumumab has been established.
Up to approximately 56 patients will be treated at the MTD level of panitumumab as established in the phase I part of the study.
Based on the historic data of patients with pancreatic cancer treated with gemcitabine based chemoradiation, we aim to increase the number of patients who are alive and progression free at 7 months from the historical value of 50% to 70% with the combination treatment of chemoradiation plus panitumumab.
|Contact: Henk MW Verheul, MD, PhDfirstname.lastname@example.org|
|VU University Medical Center||Recruiting|
|Amsterdam, Netherlands, 1081HV|
|Contact: Henk MW Verheul, MD, PhD +31-20-4444321 email@example.com|
|Principal Investigator: Henk MW Verheul, MD, PhD|
|Principal Investigator:||Henk MW Verheul, MD, PhD||VU University Medical Center|