Clinical trial NCT00381706
Conditions: Esophageal Cancer
Keywords: squamous cell carcinoma of the esophagus adenocarcinoma of the esophagus stage IV esophageal cancer recurrent esophageal cancer
Sponsor: Alliance for Clinical Trials in Oncology
Start date: 2006-09-15; Completion date: 2014-10-15
Enrollment: 245 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving more than one chemotherapy drug (combination chemotherapy) together with cetuximab may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying three different combination chemotherapy regimens to compare how well they work when given together with cetuximab in treating patients with metastatic esophageal cancer or gastroesophageal junction cancer.

Detailed description:
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to histology (squamous cell carcinoma vs adenocarcinoma) and Eastern Cooperative Oncology Group (ECOG) performance status (0 or 1 vs 2). Patients are randomized to 1 of 3 treatment arms. For more information please see the "Arms" section which includes a detailed description of the treatment regimens.

The primary objective of the study is evaluate the tumor response rate (RR) for each of the regimens in this trial and to select the most promising regimen based on RR for further testing in patients with metastatic esophageal or GE junction adenocarcinoma. The secondary objectives are:

1. To evaluate overall survival (OS) for each of the regimens in this trial in patients with metastatic esophageal or GE junction adenocarcinoma.
2. To evaluate progression-free survival (PFS) for each of the regimens in this trial in patients with metastatic esophageal or GE junction adenocarcinoma.
3. To evaluate time to treatment failure (TTF) for each of the regimens in this trial in patients with metastatic esophageal or GE junction adenocarcinoma.
4. To determine the type and severity of toxicities associated with each of these regimens in the multi-institutional phase II setting.
5. Quantitative immunohistochemistry results will be correlated with objective response rate, overall survival and time to progression.
6. To evaluate the cellular damage (apoptosis) as a result of oxaliplatin.
7. To determine if germline EGFR variants correlate with skin rash in patients treated with cetuximab.
8. To evaluate if a correlation exists between germline EGFR variants and tumor EFGR expression as measured by immunohistochemistry.

All subjects must be premedicated with diphenhydramine hydrochloride 50 mg IV (or a similar agent) prior to the first dose of cetuximab in an effort to minimize infusion and hypersensitivity reactions. Premedication is recommended prior to subsequent doses, but the dose of diphenhydramine (or similar agent) may be reduced at the investigator's discretion. More information is detailed in the protocol including a description of the premedication requirements. Patients were closely monitored for treatment-related adverse events. After completion of study treatment, patients are followed periodically for up to 2 years.

Arms: arm 1: Patients receive cetuximab 400 mg/m\^2 IV over 120 minutes on day 1 of the first cycle, then 250 mg/m\^2 IV over 60 minutes thereafter. Patients receive cetuximab IV on days 1, 8 and 15. Patients receive epirubicin 50 mg/m\^2 IV after cetuximab on day 1 followed by cisplatin 60 mg/m\^2 IV over 60 minutes. On days 1-21, patients receive 5-fluorouracil 200 mg/m\^2/day continuous IV infusion. Treatment repeats every 21 days in the absence of disease progression and unacceptable toxicity. arm 2: Patients receive cetuximab 400 mg/m\^2 IV over 120 minutes on day 1 of the first cycle, then 250 mg/m\^2 IV over 60 minutes thereafter. Patients receive cetuximab on days 1, 8 and 15. Patients receive cisplatin 30 mg/m\^2 IV over 30 minutes on days 1 and 8 after cetuximab. Patients also receive irinotecan 65 mg/m\^2 IV over 90 minutes on days 1 and 8 after receiving cisplatin.Treatment repeats every 21 days in the absence of disease progression and unacceptable toxicity. arm 3: Patients receive cetuximab 400 mg/m\^2 IV over 120 minutes on day 1 of the first cycle, then 250 mg/m\^2 IV over 60 minutes thereafter. Patients receive cetuximab on days 1 and 8. On Day 1, patients also receive oxaliplatin 85 mg/m\^2 IV over 120 minutes and leucovorin 400 mg/m\^2 IV over 120 minutes either concurrently with oxaliplatin via a separate infusion line or post oxaliplatin administration. Following leucovorin, patients will receive 5-fluorouracil 400 mg/m\^2 IV bolus injection, then 5-fluorouracil 2400 mg/m\^2 IV infusion over 46-48 hours. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: cetuximab intervention 2: ECF intervention 3: IC intervention 4: FOLFOX
Intervention descriptions: intervention 1: given IV intervention 2: epirubicin and 5-fluorouracil given IV intervention 3: cisplatin and irinotecan given IV intervention 4: oxaliplatin , leucovorin and 5-fluorouracil IV

Protocol documents: