Paclitaxel, Cisplatin, and Radiation Therapy With or Without Cetuximab in Treating Patients With Locally Advanced Esophageal Cancer - Full Text View

Sponsors and Collaborators:	Radiation Therapy Oncology Group National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00655876

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 III

Study Type:	Interventional
Study Design:	Treatment, Randomized
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders Radiation Therapy

Drug Information available for: Cisplatin Paclitaxel Cetuximab

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Overall survival (failure: death due to any cause) [ Designated as safety issue: No ]

Secondary Outcome Measures:

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:	December 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: 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.	Biological: cetuximab Given IV Drug: cisplatin Given IV Drug: paclitaxel Given IV Radiation: radiation therapy Given 5 days a week for 5½ weeks
Arm II: Active Comparator 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 ≥ 5cm), and disease status of celiac nodes (present vs absent).

Patients are randomized to 1 of 2 treatment arms.

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 and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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
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 ≤ 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00655876

Show 114 Study Locations

Sponsors and Collaborators

Radiation Therapy Oncology Group

National Cancer Institute (NCI)

Investigators

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:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Featured trial article This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Radiation Therapy Oncology Group ( Walter John Curran, Jr )
Study ID Numbers:	CDR0000538085, RTOG-0436
Study First Received:	April 9, 2008
Last Updated:	September 8, 2009
ClinicalTrials.gov Identifier:	NCT00655876 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage II esophageal cancer
stage III esophageal cancer
stage IV esophageal cancer
adenocarcinoma of the esophagus
squamous cell carcinoma of the esophagus

Study placed in the following topic categories:

Digestive System Neoplasms
Gastrointestinal Diseases
Esophageal Neoplasms
Cetuximab
Esophageal Cancer
Antimitotic Agents
Squamous Cell Carcinoma
Carcinoma
Digestive System Diseases
Radiation-Sensitizing Agents
Cisplatin

Paclitaxel
Esophageal Disorder
Head and Neck Neoplasms
Tubulin Modulators
Epidermoid Carcinoma
Gastrointestinal Neoplasms
Esophageal Diseases
Carcinoma, Squamous Cell
Adenocarcinoma
Antineoplastic Agents, Phytogenic

Additional relevant MeSH terms:

Digestive System Neoplasms
Molecular Mechanisms of Pharmacological Action
Gastrointestinal Diseases
Antineoplastic Agents
Esophageal Neoplasms
Mitosis Modulators
Physiological Effects of Drugs
Cetuximab
Antimitotic Agents
Pharmacologic Actions
Neoplasms

Digestive System Diseases
Neoplasms by Site
Radiation-Sensitizing Agents
Cisplatin
Paclitaxel
Therapeutic Uses
Head and Neck Neoplasms
Tubulin Modulators
Gastrointestinal Neoplasms
Esophageal Diseases
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on September 09, 2009