Cetuximab and Radiation Therapy for Surgically Resectable Esophageal and Gastroesophageal (GE) Junction Carcinomas

This study has been completed.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Walther Cancer Institute
Information provided by:
Hoosier Cancer Research Network
ClinicalTrials.gov Identifier:
NCT00319735
First received: April 27, 2006
Last updated: April 28, 2011
Last verified: April 2011
  Purpose

The interaction of epidermal growth factor receptor (EGFR) inhibitory agents such as cetuximab combined with radiation shows promising results. EGFR inhibitory agents also enhance radiation-induced apoptosis and inhibit radiation induced damage repair. These interactions may represent the principle effects that contribute to the synergy between EGFR and radiation.

This trial will investigate the feasibility and activity of this combination in patients with surgically resectable disease.


Condition Intervention Phase
Esophageal Cancer
Procedure: Radiation Therapy
Procedure: Surgery
Procedure: Tissue Sample
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study With Cetuximab and Radiation Therapy for Patients With Surgically Resectable Esophageal and GE Junction Carcinomas: Hoosier Oncology Group Study (GI05-92)

Resource links provided by NLM:


Further study details as provided by Hoosier Cancer Research Network:

Primary Outcome Measures:
  • · To evaluate complete pathologic response rate in patients with esophageal and GE junction carcinomas [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate complete and partial response rate of preoperative radiation and cetuximab in patients with esophageal and GE junction carcinomas [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • To evaluate time to relief of dysphagia in patients with esophageal and GE junction carcinomas receiving preoperative radiation and cetuximab [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • To evaluate the overall toxicities of preoperative radiation and cetuximab in patients with esophageal and GE junction carcinomas [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
  • To perform exploratory molecular correlates to determine the mechanisms of response and resistance to cetuximab and radiation therapy. [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Enrollment: 41
Study Start Date: April 2006
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Cetuximab 400 mg/m2 IV over 120 minutes Day -14 (Loading Dose) Cetuximab 250 mg/m2 IV over 60 minutes Day -7 Cetuximab 250 mg/m2 IV over 60 minutes Days 1, 8, 15, 22, 29 and 36
Procedure: Radiation Therapy
External beam radiation therapy, beginning on day 1, 4500 cGy to esophagus with boost of 540 cGy at 180 cGy per fraction for 6 weeks
Procedure: Surgery
Surgical resection of primary tumor and adjacent mediastinal and/or celiac lymph nodes by a transthoracic approach after satisfactory hematologic and functional recovery within 8 weeks of completion of radiation therapy
Procedure: Tissue Sample
For patients who give their consent, fresh frozen tissue will be obtained per EUS at baseline, per EUS 2 weeks after the initiation of chemotherapy, and at the time of surgery for pathology submission

Detailed Description:

OUTLINE: This is a multi-center study.

  • Cetuximab 400 mg/m2 IV over 120 minutes Day -14 (Loading Dose)
  • Cetuximab 250 mg/m2 IV over 60 minutes, day -7.
  • Cetuximab 250 mg/m2 IV over 60 minutes, days 1, 8, 15, 22, 29 and 36.
  • External beam radiation therapy, beginning on day 1, 4500 cGy to esophagus with boost of 540 cGy at 180 cGy per fraction for 6 weeks.
  • Surgical resection of primary tumor and adjacent mediastinal and/or celiac lymph nodes by a transthoracic approach after satisfactory hematologic and functional recovery within 8 weeks of completion of radiation therapy.
  • For patients who give their consent, fresh frozen tissue will be obtained per EUS at baseline, per EUS 2 weeks after the initiation of cetuximab, and at the time of surgery for pathology submission.
  Eligibility

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

Inclusion Criteria:

  • Pathological diagnosis of either squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction.
  • Clinical stage IIA, IIB or III without metastatic disease
  • Patients must have documented EGFR status or have tumor tissue available for assessment of EGFR status by IHC
  • Patients must be surgical candidates as determined by surgical consult.
  • Patients must agree to surgery.
  • ECOG performance status 0 or 2
  • Absolute neutrophil count (ANC) > 1,000 mm3
  • Platelet count > 75,000 mm3· Hemoglobin > 10g/dL
  • Bilirubin < 2.5 X upper limit of normal
  • AST (SGOT) or ALT (SGPT) < 5.0 ´ upper limit of normal
  • Creatinine < 2.0 X upper limit of normal

Exclusion Criteria:

  • No history of or current brain metastasis.
  • No significant history of uncontrolled cardiac disease; i.e. uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.
  • No history of interstitial pneumonitis or pulmonary fibrosis, or suspicion of interstitial pneumonitis or pulmonary fibrosis on imaging.
  • No concurrent chemotherapy not indicated in the study protocol or any other investigational agent(s).
  • No prior use of radiation or chemotherapy for cancer of the esophagus or GE junction
  • No prior therapy that specifically and directly targets the EGFR pathway (such as kinase inhibitors and antibodies directed against the HER family receptors).
  • No prior severe infusion reaction to a monoclonal antibody.
  • No major surgery within 28 days prior to being registered for protocol therapy.
  • No clinically significant infections as judged by the treating investigator.
  • No acute hepatitis or known HIV.
  • No other active malignancies.
  • Negative pregnancy test.
  • No female patients currently breastfeeding.
  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: NCT00319735

Locations
United States, Illinois
Medical & Surgical Specialists, LLC
Galesburg, Illinois, United States, 61401
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202
Community Regional Cancer Center
Indianapolis, Indiana, United States, 46256
AP&S Clinic
Terre Haute, Indiana, United States, 47804
United States, Missouri
Siteman Cancer Center
St. Louis, Missouri, United States, 63110
United States, Texas
Texas Oncology, PA
Dallas, Texas, United States, 75246
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75390
Sponsors and Collaborators
Hoosier Cancer Research Network
Bristol-Myers Squibb
Walther Cancer Institute
Investigators
Study Chair: Carlos Becerra, M.D. Hoosier Oncology Group, LLC
Study Chair: Nasser Hanna, M.D. Hoosier Oncology Group, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Nasser Hanna, M.D., Hoosier Oncology Group
ClinicalTrials.gov Identifier: NCT00319735     History of Changes
Other Study ID Numbers: HOG GI05-92
Study First Received: April 27, 2006
Last Updated: April 28, 2011
Health Authority: United States: Institutional Review Board

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
Cetuximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014