Clinical trial NCT00911820
Conditions: Esophageal Cancer Gastric Cancer Stomach Cancer
Sponsor: Dana-Farber Cancer Institute
Start date: 2009-07-01; Completion date: 2013-08-01
Enrollment: 88 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
There is no clear standard of care for metastatic stomach or esophageal cancer in the United States. The purpose of this research study is to determine the differences between two regimens of chemotherapy; Arm A: PCA (Cisplatin, Irinotecan and Bevacizumab) and Arm B: TPCA (Docetaxel, Cisplatin, Irinotecan and Bevacizumab). Docetaxel, Cisplatin, and Irinotecan are traditional chemotherapy drugs. Bevacizumab is an antibody (a protein that attacks a foreign substance in the body). Bevacizumab is believed to stop the formation of new blood vessels that carry nutrients to tumors. Both of the chemotherapy regimens (PCA and TPCA) have been studied in patients with esophageal and gastric cancer, and we are trying to determine if one regimen will keep your cancer from growing and improve how long you can live.

Detailed description:
OBJECTIVES:

Primary

\* To evaluate progression-free survival at 7 months in metastatic esophageal and gastric patients treated with either PCA or TPCA

Secondary

* To determine overall survival
* To determine the response rate (RECIST) in measurable disease patients
* To evaluate type and severity of toxicities associated with each regimen

Exploratory:

* To correlate expression of tumoral and serum VEGF with response and survival
* To correlate TGF alpha levels and tumor microvessel density with clinical activity of the combination of PCA or TPCA
* To examine circulating endothelial cells (CECs) as surrogate markers of antitumor activity of bevacizumab
* To explore if 7/7 and 7/6 UGT1A1 polymorphisms correlate with grade III/IV irinotecan-related diarrhea and neutropenia when irinotecan is given at relatively low dose to patients with esophageal and gastric cancer

DESIGN:

This trial was designed to compare 7-month progression-free survival between arms. The hypothesis was that TPCA would have superior outcome over PCA (70% vs 50%). With 40 eligible patients per arm followed for 1 year there was 80% power to detect a hazard ratio of 0.48 using the log-rank test at a one-sided type I error rate of 5%. Stratification factors were ECOG performance status 0/1 vs 2 and site of primary tumor (gastric vs GE junction/esophageal).

Arms: arm 1: Patients first received bevacizumab 10 mg/kg IV on day 1 of every cycle (cycle length=21 days) at approximately 0.5 mg/kg/minute. Additionally, on days 1 and 8 of each cycle, patients received cisplatin 30 mg/m2 IV over 30 minutes and then irinotecan 65 mg/m2 IV over 30 minutes of each 3-week cycle. Treatment could continue until disease progression or unacceptable toxicity. arm 2: Patients first received bevacizumab 10 mg/kg IV on day 1 of every cycle (cycle length=21 days) at approximately 0.5 mg/kg/minute. Additionally on days 1 and 8 of each cycle, patients received docetaxel 30 mg/m2 IV over 30 minutes followed by cisplatin 25 mg/m2 IV over 30 minutes and then irinotecan 50 mg/m2 IV over 30 minutes of each 3-week cycle.
Interventions: intervention 1: Bevacizumab intervention 2: Cisplatin intervention 3: Irinotecan intervention 4: Docetaxel
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None

Protocol documents: