Paclitaxel, Cisplatin, and Radiation Therapy With or Without Cetuximab in Treating Patients With Locally Advanced Esophageal Cancer
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Esophageal Cancer |
Biological: cetuximab Drug: cisplatin Drug: paclitaxel Radiation: radiation therapy |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Primary Purpose: Treatment |
| 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 |
- Overall survival (failure: death due to any cause) [ Designated as safety issue: No ]
- Local control (failure: residual cancer on post-treatment endoscopic biopsy or recurrent primary disease as defined in protocol) [ Designated as safety issue: No ]
- Adverse events as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
- Endoscopic complete response rate [ Designated as safety issue: No ]
- Health-related quality of life (FACT-E) [ Designated as safety issue: No ]
- Quality-adjusted survival (using EQ-5D), if primary hypothesis is supported [ Designated as safety issue: No ]
- Tissue handling/storage for future studies [ Designated as safety issue: No ]
| Estimated Enrollment: | 420 |
| Study Start Date: | June 2008 |
| Estimated Primary Completion Date: | August 2018 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 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.
|
Biological: cetuximab
Given IV
Drug: cisplatin
Given IV
Drug: paclitaxel
Given IV
Radiation: radiation therapy
Given 5 days a week for 5½ weeks
|
|
Active Comparator: Arm II
Patients receive paclitaxel and cisplatin as in arm I. Patients also undergo radiotherapy as in arm I.
|
Drug: cisplatin
Given IV
Drug: paclitaxel
Given IV
Radiation: radiation therapy
Given 5 days a week for 5½ weeks
|
Detailed 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.
Eligibility| Ages Eligible for Study: | 18 Years to 74 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Show 175 Study Locations| Study Chair: | Mohan Suntharalingam, MD | University of Maryland Greenebaum Cancer Center |
| Investigator: | David H. Ilson, MD, PhD | Memorial Sloan-Kettering Cancer Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | Walter John Curran, Jr, Radiation Therapy Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00655876 History of Changes |
| Other Study ID Numbers: | CDR0000538085, RTOG-0436 |
| Study First Received: | April 9, 2008 |
| Last Updated: | September 28, 2012 |
| Health Authority: | Unspecified |
Keywords provided by National Cancer Institute (NCI):
|
stage IIA esophageal cancer stage IIB esophageal cancer stage IIIA esophageal cancer stage IIIB esophageal cancer |
stage IIIC esophageal cancer stage IV esophageal cancer squamous cell carcinoma of the esophagus |
Additional relevant MeSH terms:
|
Esophageal Diseases Esophageal Neoplasms Gastrointestinal Diseases Digestive System Diseases Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Head and Neck Neoplasms Cetuximab Cisplatin |
Paclitaxel Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Radiation-Sensitizing Agents Physiological Effects of Drugs Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Phytogenic |
ClinicalTrials.gov processed this record on June 18, 2013