Overview

This trial is active, not recruiting.

Condition esophageal cancer
Treatments cetuximab, cisplatin, paclitaxel, radiation therapy
Phase phase 3
Target EGFR
Sponsor Radiation Therapy Oncology Group
Collaborator National Cancer Institute (NCI)
Start date June 2008
End date August 2018
Trial size 420 participants
Trial identifier NCT00655876, CDR0000538085, RTOG 0436

Summary

RATIONALE: Drugs used in chemotherapy, such as paclitaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. 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. Cetuximab may stop the growth of esophageal cancer by blocking blood flow to the tumor. It is not yet known whether giving paclitaxel and cisplatin together with radiation therapy is more effective with or without cetuximab in treating esophageal cancer.

PURPOSE: This randomized phase III trial is comparing how well giving paclitaxel and cisplatin together with radiation therapy works with or without cetuximab in treating patients with locally advanced esophageal cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
Patients receive cetuximab IV over 1-2 hours, paclitaxel IV over 1 hour, and cisplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Patients also undergo radiotherapy once daily, 5 days a week, for 5½ weeks.
cetuximab
Given IV
cisplatin
Given IV
paclitaxel
Given IV
radiation therapy
Given 5 days a week for 5½ weeks
(Active Comparator)
Patients receive paclitaxel and cisplatin as in arm I. Patients also undergo radiotherapy as in arm I.
cisplatin
Given IV
paclitaxel
Given IV
radiation therapy
Given 5 days a week for 5½ weeks

Primary Outcomes

Measure
Overall survival (failure: death due to any cause)
time frame: From randomization to the date of death or last follow-up for up to 10 years

Secondary Outcomes

Measure
Local control (failure: residual cancer on post-treatment endoscopic biopsy or recurrent primary disease as defined in protocol)
time frame: From randomization to the date of disease progression for up to 10 years
Adverse events as assessed by NCI CTCAE v3.0
time frame: From randomization to the date of death or last follow-up for up to 10 years
Endoscopic complete response rate
time frame: From randomization to 11- 14 weeks
Health-related quality of life (FACT-E)
time frame: Less than 14 days prior to registration, 6-8 weeks, 1 year and 2 years post treatment
Quality-adjusted survival (using EQ-5D), if primary hypothesis is supported
time frame: Less than 14 days prior to registration, 6-8 weeks, 1 year and 2 years post treatment

Eligibility Criteria

Male or female participants from 18 years up to 74 years old.

DISEASE CHARACTERISTICS: - Histologically confirmed primary squamous cell or adenocarcinoma* of the esophagus or gastroesophageal junction - Patients with involvement of the gastroesophageal junction with Siewert type I or II tumors (tumors arising from the distal esophagus and involving the esophagogastric junction or tumors starting at the esophagogastric junction and involving the cardia) are eligible - Patients with cervical esophageal carcinoma are eligible - Patients with celiac, perigastric, mediastinal, or supraclavicular adenopathy are eligible NOTE: * The adenocarcinoma stratum is closed as of 5/3/2012. - Stage T1, N1, M0; T2-4, Any N, M0; or Any T, Any N, M1a disease based on history/physical examination, endoscopy with biopsy, AND PET/PET-CT scan or chest/abdominal CT scan within 6 weeks prior to registration - Disease must be encompassed in a radiotherapy field - No evidence of tracheoesophageal fistulas or invasion into the trachea or major bronchi - Patients with T3-4 proximal thoracic esophageal tumors (15-25 cm) must undergo bronchoscopy to exclude fistula PATIENT CHARACTERISTICS: - Zubrod performance status 0-2 - ANC ≥ 1,500/mm³ - Platelets ≥ 100,000 cells/mm³ - Hemoglobin ≥ 8.0 g/dL (transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL allowed) - Creatinine ≤ 1.5 mg/dL - Bilirubin ≤ 1.5 times upper limit of normal (ULN) - AST or ALT ≤ 3 times ULN - Negative pregnancy test - Not pregnant or nursing - Fertile patients must use effective contraception - Total intake (oral/enteral) must be ≥ 1,500 kCal/day - No prior invasive malignancy except nonmelanomatous skin cancer (e.g., carcinoma in situ of the breast, oral cavity, or cervix) unless disease-free for ≥ 2 years - No prior allergic reaction to the study drugs - No prior severe infusion reaction to a monoclonal antibody - No severe, active comorbidity, including any of the following: - Unstable angina and/or congestive heart failure requiring hospitalization within the past 3 months - Transmural myocardial infarction within the past 6 months - Acute bacterial or fungal infection requiring intravenous antibiotics - Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy - Acquired immune deficiency syndrome based upon current CDC definition - HIV testing is not required for entry into this study PRIOR CONCURRENT THERAPY: - No prior systemic chemotherapy for esophageal cancer (prior chemotherapy for another cancer allowed) - No prior therapy that specifically and directly targets the EGFR pathway - No prior platinum-based and/or paclitaxel-based therapy - No prior radiotherapy that would result in overlap of planned study radiotherapy fields - No concurrent investigational agent - No concurrent cytotoxic agent - No other concurrent radiotherapy

Additional Information

Official title A Phase III Trial Evaluating the Addition of Cetuximab to Paclitaxel, Cisplatin, and Radiation for Patients With Esophageal Cancer Who Are Treated Without Surgery
Principal investigator Mohan Suntharalingam, MD
Description OBJECTIVES: Primary - To evaluate whether the addition of cetuximab to chemotherapy comprising paclitaxel, cisplatin, and radiotherapy improves overall survival compared with paclitaxel, cisplatin, and radiotherapy alone in patients with esophageal cancer treated without surgery. Secondary - To evaluate whether the addition of cetuximab to paclitaxel, cisplatin, and radiotherapy improves local control by increasing the clinical complete response and decreasing local recurrence in these patients. - To evaluate adverse events in these patients. - To evaluate endoscopic complete response rates in these patients. - To evaluate if the addition of cetuximab to paclitaxel, cisplatin, and radiotherapy improves the Esophageal Cancer Subscale score of the FACT-E quality of life tool. - To evaluate the quality-adjusted survival of each treatment arm using EQ-5D if the primary endpoint supports the primary hypothesis. OUTLINE: This is a multicenter study. Patients are stratified according to histology (adenocarcinoma* vs squamous), cancer lesion size (< 5 cm vs ≥ 5 cm), and disease status of celiac nodes (present vs absent). Patients are randomized to 1 of 2 treatment arms. NOTE: * The adenocarcinoma stratum is closed as of 5/3/2012. - Arm I: Patients receive cetuximab IV over 1-2 hours, paclitaxel IV over 1 hour, and cisplatin IV over 30-60 minutes on days 1, 8, 15, 22, 29, and 36. Patients also undergo radiotherapy once daily, 5 days a week, for 5½ weeks for a total dose of 50.4Gy. - Arm II: Patients receive paclitaxel and cisplatin as in arm I. Patients also undergo radiotherapy as in arm I. Patients undergo endoscopy 6 to 8 weeks after completion of chemoradiotherapy. Quality of life is assessed at baseline, within 1 week of post-treatment endoscopy, and at 1 and 2 years from beginning of study treatment. After completion of study treatment, patients are followed periodically.
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by Radiation Therapy Oncology Group.