Combining Erlotinib Plus Bevacizumab and Gemcitabine Plus Capecitabine to Treat Advanced Pancreatic Cancer (TARGET)
Recruitment status was Active, not recruiting
Pancreatic cancer is an aggressive, largely chemo-resistant disease with a poor prognosis. EGFR and VEGF are both overexpressed in pancreatic cancers and thought to contribute to tumour development and progression. The combination of gemcitabine and capecitabine has recently been shown to be effective in advanced pancreatic cancer. The combination of gemcitabine plus erlotinib has also been shown to be effective in advanced pancreatic cancer. The aim of this study is to assess whether combining a chemotherapy doublet (gemcitabine plus capecitabine) and a biologic doublet (erlotinib plus bevacizumab) is a safe and effective way to treat advanced pancreatic cancer by targeting multiple tumour stimulating mechanisms simultaneously.
Drug: Gemcitabine 1000 mg/m2 iv days 1, 8, 15 of a 28 day cycle
Drug: Capecitabine orally days 1 -21
Drug: Erlotinib 100 mg orally days 1-28
Drug: Bevacizumab 5 mg/kg intravenously every 2 weeks
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I-II Dose Finding and Early Efficacy Study of Combination Therapy With Erlotinib (Tarceva), Gemcitabine, Bevacizumab (Avastin), and Capecitabine in Advanced Pancreatic Cancer|
- Part A (Phase I): Dose-limiting Toxicity (DLT)
- Part B (Phase II): Overall response rate (complete response and partial response)
- The secondary efficacy objectives of the trial are: One year survival and median overall survival
- Progression free survival, Disease control rate.
- The secondary safety objectives are: Toxicity,Quality of life
- and Assessment of pain
|Study Start Date:||November 2005|
|Estimated Study Completion Date:||December 2009|
To establish the safety and efficacy of a combination of four drugs (capecitabine, gemcitabine, erlotinib and bevacizumab) in the treatment of patients with locally advanced or metastatic pancreatic cancer. The study will be divided into two parts:
Part A (Phase I ): Is to establish the optimal dose of capecitabine for combination with gemcitabine, bevacizumab and erlotinib. This part of the study is necessary in order to characterise any increased side effects that may occur as a result of this combination of drugs. The dose of capecitabine will be increased in cohorts containing 3 to 6 patients(according to standard dose escalation study design) whilst side effects are closely monitored. The doses of the other three drugs will remain fixed during this period:
- Gemcitabine: 1000 mg/m2 Days 1, 8, 15
- Bevacizumab: 5 mg/kg every two weeks iv
- Erlotinib: 100 mg/day orally
Maximum tolerated dose is the dose at which 2 out of a cohort of three to six patients experience dose-limiting toxicity within the first cycle (28 days) of treatment. The recommended dose for further evaluation will be one dose level below this.
Part B (Phase II): Once a recommended dose of capecitabine has been chosen, this will be used for the remainder of the trial to further characterise the efficacy and safety of the drug combination in this group of patients.
|The Royal Marsden Foundation Hospital NHS Trust|
|London and Surrey, London, United Kingdom, SM2 5PT|
|Principal Investigator:||David Cunningham, MD, FRCP||The Royal Marsden Hospital NHS Foundation Trust|