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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Eastern Cooperative Oncology Group
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00381706
First received: September 26, 2006
Last updated: March 15, 2011
Last verified: June 2009
  Purpose

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.


Condition Intervention Phase
Esophageal Cancer
Biological: cetuximab
Drug: cisplatin
Drug: epirubicin hydrochloride
Drug: fluorouracil
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Drug: oxaliplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: Randomized Phase II Study of ECF-C, IC-C, or FOLFOX-C in Metastatic Esophageal and GE Junction Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Tumor response rate (complete and partial) in patients with measurable esophageal or GE junction adenocarcinoma [ Designated as safety issue: No ]
  • Tumor response rate (complete and partial) in patients with adenocarcinoma who have received at least 1 treatment course as measured by RECIST criteria [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Tumor response rate (complete and partial) in patients with squamous cell carcinoma [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Time to treatment failure [ Designated as safety issue: No ]

Estimated Enrollment: 270
Study Start Date: September 2006
Estimated Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (ECF + cetuximab)
Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15; epirubicin hydrochloride IV followed by cisplatin IV over 1 hour on day 1; and fluorouracil IV continuously on days 1-21. Treatment repeats every 21 days in the absence of disease progression and unacceptable toxicity.
Biological: cetuximab
given IV
Drug: cisplatin
given IV
Drug: epirubicin hydrochloride
given IV
Experimental: Arm II (IC + cetuximab)
Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15 and cisplatin IV over 30 minutes followed by irinotecan hydrochloride IV over 90 minutes on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Biological: cetuximab
given IV
Drug: cisplatin
given IV
Drug: irinotecan hydrochloride
given IV
Experimental: ARM III (FOLFOX + cetuximab)
Patients receive cetuximab IV over 1-2 hours on days 1 and 8; oxaliplatin IV over 2 hours followed by leucovorin calcium IV over 2 hours on day 1; and fluorouracil IV continuously over 46-48 hours on days 1 and 2. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.
Biological: cetuximab
given IV
Drug: fluorouracil
given IV
Drug: leucovorin calcium
given IV
Drug: oxaliplatin
given IV

Detailed Description:

OBJECTIVES:

Primary

  • Compare the tumor response rate in patients with metastatic esophageal or gastroesophageal junction cancer treated with epirubicin hydrochloride, cisplatin, fluorouracil, and cetuximab (ECF-C); irinotecan hydrochloride, cisplatin, and cetuximab (IC-C); or fluorouracil, oxaliplatin, leucovorin calcium, and cetuximab (FOLFOX-C).

Secondary

  • Compare overall survival of patients treated with these regimens.
  • Compare progression-free survival of patients treated with these regimens.
  • Compare treatment failure in patients treated with these regimens.
  • Determine the type and severity of toxicities associated with these regimens in the multi-institutional phase II setting.
  • Correlate quantitative immunohistochemistry results with objective response rate, overall survival, and time to progression in these patients.
  • Evaluate the cellular damage (i.e., apoptosis) as a result of oxaliplatin in these patients.
  • Determine if germline epidermal growth factor receptor (EGFR) variants correlate with skin rash in patients treated with cetuximab.
  • Correlate germline EGFR variants with tumor EGFR expression as measured by immunohistochemistry.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to histology (squamous cell carcinoma vs adenocarcinoma) and ECOG performance status (0 or 1 vs 2). Patients are randomized to 1 of 3 treatment arms.

  • Arm I (ECF + cetuximab): Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15; epirubicin hydrochloride IV followed by cisplatin IV over 1 hour on day 1; and fluorouracil IV continuously on days 1-21. Treatment repeats every 21 days in the absence of disease progression and unacceptable toxicity.
  • Arm II (IC + cetuximab): Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15 and cisplatin IV over 30 minutes followed by irinotecan hydrochloride IV over 90 minutes on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
  • ARM III (FOLFOX + cetuximab): Patients receive cetuximab IV over 1-2 hours on days 1 and 8; oxaliplatin IV over 2 hours followed by leucovorin calcium IV over 2 hours on day 1; and fluorouracil IV continuously over 46-48 hours on days 1 and 2. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.

Patients undergo tumor sample collection at baseline to examine quantitative immunofluorescence with subcellular localization for epidermal growth factor receptor (EGFR), phospho EGFR, HER-2, phospho-HER-2, HER-3, HER-4, FEF, AKT, phospho AKT, PTEN, gastrin-releasing peptide (GRP), and GRP receptor levels. Tumor samples are collected at baseline from patients randomized to arm III to evaluate molecular mechanisms for correlative studies. Cellular damage (i.e., apoptosis) by oxaliplatin is determined by DNA fragmentation by TUNEL assay.

After completion of study treatment, patients are followed periodically for up to 2 years.

PROJECTED ACCRUAL: A total of 270 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically, cytologically, or radiologically confirmed esophageal cancer, including any of the following types:

    • Squamous cell carcinoma
    • Adenocarcinoma* of the esophagus
    • Adenocarcinoma* of the gastroesophageal (GE) junction according to Siewert classification

      • Type I or II disease

        • No type III disease NOTE: Undifferentiated adenocarcinoma and adenosquamous tumor will be considered as adenocarcinoma
  • Metastatic disease or locally recurrent or residual (post-resection) disease

    • Resected esophageal or GE junction disease that develops radiological or clinical evidence of metastatic disease does not require histological or cytological confirmation of metastatic disease unless 1 of the following is true:

      • More than 5 years since primary surgery and development of metastatic disease
      • Primary cancer was stage I
  • Measurable disease, defined as at least 1 unidimensionally measurable lesion (longest diameter) as ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
  • Must have ≥ 1 paraffin block (or ≥ 15 unstained slides) available for analysis of tumor epidermal growth factor receptor (EGFR) status
  • No known CNS metastases or carcinomatous meningitis

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Platelet count ≥ 100,000/mm^3
  • Granulocyte count ≥ 1,500/mm^3
  • Creatinine ≤ 1.5 mg/dL
  • AST ≤ 5.0 times upper limit of normal
  • Bilirubin ≤ 1.5 mg/dL
  • Albumin ≥ 2.5 g/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Must have a stable weight loss of (i.e., < 1 pound weight loss during the past week)
  • No diarrhea ≥ grade 2 within the past 7 days
  • No myocardial infarction within the past 6 months
  • No New York Heart Association class III or IV congestive heart failure
  • No interstitial pneumonia or symptomatic interstitial fibrosis of the lung
  • No seizure disorder or active neurological disease requiring anti-epileptic medication
  • No peripheral neuropathy ≥ grade 2
  • No evidence of Gilbert's syndrome
  • No prior allergic reaction to chimerized or murine monoclonal antibody therapy or documented presence of human anti-mouse antibodies (HAMA)

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior chemotherapy or radiotherapy
  • No prior therapy that specifically and directly targets the EGFR pathway
  • At least 4 weeks since prior major surgery* and recovered
  • At least 2 weeks since prior minor surgery* and recovered
  • No concurrent palliative radiotherapy
  • No other concurrent investigational agent
  • No other concurrent chemotherapy
  • No concurrent hormonal therapy except for the following:

    • Steroids given temporarily for adrenal failure
    • Hormones for nondisease-related conditions (e.g., insulin for diabetes)
    • Intermittent steroids (e.g., dexamethasone) as an antiemetic NOTE: *Insertion of a vascular device is not considered major or minor surgery
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00381706

  Show 227 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
Investigators
Study Chair: Peter C. Enzinger, MD Dana-Farber Cancer Institute
Investigator: David H. Ilson, MD, PhD Memorial Sloan-Kettering Cancer Center
Study Chair: Barbara A. Burtness, MD Fox Chase Cancer Center
  More Information

Additional Information:
Publications:
Enzinger PC, Burtness B, Hollis D, et al.: CALGB 80403/ECOG 1206: A randomized phase II study of three standard chemotherapy regimens (ECF, IC, FOLFOX) plus cetuximab in metastatic esophageal and GE junction cancer. [Abstract] J Clin Oncol 28 (Suppl 15): A-4006, 2010.

Responsible Party: Monica M. Bertagnolli, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier: NCT00381706     History of Changes
Other Study ID Numbers: CDR0000505535, CALGB-80403, ECOG-E1206
Study First Received: September 26, 2006
Last Updated: March 15, 2011
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
squamous cell carcinoma of the esophagus
adenocarcinoma of the esophagus
stage IV esophageal cancer
recurrent esophageal cancer

Additional relevant MeSH terms:
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Oxaliplatin
Irinotecan
Cetuximab
Cisplatin
Epirubicin
Fluorouracil
Camptothecin
Leucovorin
Levoleucovorin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Vitamin B Complex

ClinicalTrials.gov processed this record on July 22, 2014