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

NCT00319735 | Completed Phase 2 Results DMC

• 1 other identifier: HOG GI05-92
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Esophageal Cancer

Outcome Measures

Primary Outcomes (1)

• Complete Pathologic Response (pCR)

  To evaluate complete pathologic response rate in patients with esophageal and GE junction carcinomas. Complete pathologic response (pCR) is defined as the absence of tumor cells on the resected specimen in the esophagus and/or GE junction.

  36 months

Secondary Outcomes (9)

• Complete Pathological Response Rate for Patients Who Underwent Esophagectomy.

  Up to 36 months

• Time to Relief of Dysphagia

  36 months

• Evaluate Toxicity

  36 months

• Perform Exploratory Molecular Correlates.

  36 months

• Complete and Partial Response Rate for Patients by Disease Stage: IIA

  36 months

Study Arms (1)

Investigational Treatment

EXPERIMENTAL

* 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 * Combined with radiation therapy for six weeks. * Surgery for esophageal resection after 6 to 8 week rest period. Subjects who consent will provide tissue samples.

Procedure: Radiation Therapy; Procedure: Surgery; Procedure: Tissue Sample

Interventions

Radiation Therapy PROCEDURE

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

Investigational Treatment

Surgery PROCEDURE

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

Investigational Treatment

Tissue Sample PROCEDURE

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

Investigational Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Nasser Hanna, M.D.: lead
• Bristol-Myers Squibb: collaborator
• Walther Cancer Institute: collaborator

Study Sites (7)

Medical & Surgical Specialists, LLC

Galesburg, Illinois, 61401, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Community Regional Cancer Center

Indianapolis, Indiana, 46256, United States

Location

AP&S Clinic

Terre Haute, Indiana, 47804, United States

Location

Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Texas Oncology, PA

Dallas, Texas, 75246, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75390, United States

Location

Related Publications (1)

• Becerra CR, Hanna N, McCollum AD, Becharm N, Timmerman RD, DiMaio M, Kesler KA, Yu M, Yan T, Choy H. A phase II study with cetuximab and radiation therapy for patients with surgically resectable esophageal and GE junction carcinomas: Hoosier Oncology Group G05-92. J Thorac Oncol. 2013 Nov;8(11):1425-9. doi: 10.1097/JTO.0b013e3182a46c3b.

  PMID: 24084441 RESULT

Related Links

• Hoosier Oncology Group Home Page

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

Radiotherapy; Surgical Procedures, Operative; Histocompatibility Testing

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Immunologic Tests; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Immunologic Techniques

Results Point of Contact

• Title: Principal Investigator
• Organization: Hoosier Cancer Research Network, Inc.

jsmith@hoosiercancer.org

317-921-2050

Study Officials

• Carlos Becerra, M.D.

  Hoosier Oncology Group, LLC

  STUDY CHAIR

• Nasser Hanna, M.D.

  Hoosier Oncology Group, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: April 27, 2006
• First Posted: April 27, 2006
• Study Start: April 1, 2006
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: April 28, 2016
• Results First Posted: April 28, 2016

Record last verified: 2016-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)