Combination Chemotherapy and Cetuximab in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer

Phase 2

Completed

Conditions: Esophageal Cancer

Interventions: Biological: cetuximab
Drug: ECF
Drug: IC
Drug: FOLFOX

Registration Number: NCT00381706

Lead Sponsor: Alliance for Clinical Trials in Oncology

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 245

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A (ECF + cetuximab)	ECF	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 C (FOLFOX + cetuximab)	cetuximab	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.
Arm A (ECF + cetuximab)	cetuximab	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 B (IC + cetuximab)	cetuximab	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 B (IC + cetuximab)	IC	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 C (FOLFOX + cetuximab)	FOLFOX	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.

Primary Outcome Measures

Name	Time	Method
Response Rate (Complete and Partial) in Patients With Measurable Esophageal or GE Junction Adenocarcinoma	Up to 2 years post-treatment	Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria. Overall tumor response is the total number of CR and PRs in participants with adenocarcinoma who have received at least one cycle of therapy.

Secondary Outcome Measures

Name	Time	Method
Tumor Response Rate (Complete and Partial) in Patients With Squamous Cell Carcinoma	Up to 2 years post-treatment	Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria. Overall tumor response is the total number of CR and PRs in participants with squamous cell carcinoma who have received at least one cycle of therapy.
Overall Survival in Patients With Adenocarcinoma	Up to 2 years post-treatment	Overall survival (OS) was defined as the time from study entry to death of any cause. The median OS with 95% CI was estimated using the Kaplan Meier method.
Progression-free Survival in Patients With Adenocarcinoma	Up to 2 years post-treatment	Progression free survival (PFS) was defined as the time from study entry to progression or death of any cause. The median PFS with 95% CI was estimated using the Kaplan Meier method.
Time to Treatment Failure in Patients With Adenocarcinoma	Up to 2 years post-treatment	Time to treatment failure (TTF) was measured from study entry until documented progression, death resulting from any cause, or end of protocol therapy because of unacceptable toxicity. The median TTF with 95% CI was estimated using the Kaplan Meier method.

Trial Locations

Locations (226): Norwalk Hospital
🇺🇸
Norwalk, Connecticut, United States
Tunnell Cancer Center at Beebe Medical Center
🇺🇸
Lewes, Delaware, United States
CCOP - Christiana Care Health Services
🇺🇸
Newark, Delaware, United States
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
🇺🇸
Washington, District of Columbia, United States
Rush-Copley Cancer Care Center
🇺🇸
Aurora, Illinois, United States
St. Joseph Medical Center
🇺🇸
Kansas City, Missouri, United States
Graham Hospital
🇺🇸
Canton, Illinois, United States
Memorial Hospital
🇺🇸
Carthage, Illinois, United States
University of Chicago Cancer Research Center
🇺🇸
Chicago, Illinois, United States
Decatur Memorial Hospital Cancer Care Institute
🇺🇸
Decatur, Illinois, United States
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Norwalk Hospital
🇺🇸Norwalk, Connecticut, United States