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

Esophageal Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00319735
• Other study ID #: HOG GI05-92
• Status: Completed
• Phase: Phase 2
• First received: April 27, 2006
• Last updated: April 28, 2011
• Start date: April 2006
• Est. completion date: January 2009

Study information

• Verified date: April 2011
• Source: Hoosier Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: January 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
United States	Texas Oncology, PA	Dallas	Texas
United States	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas
United States	Medical & Surgical Specialists, LLC	Galesburg	Illinois
United States	Community Regional Cancer Center	Indianapolis	Indiana
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Siteman Cancer Center	St. Louis	Missouri
United States	AP&S Clinic	Terre Haute	Indiana

Sponsors (3)

Lead Sponsor	Collaborator
Hoosier Cancer Research Network	Bristol-Myers Squibb, Walther Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	· To evaluate complete pathologic response rate in patients with esophageal and GE junction carcinomas		36 months	No
Secondary	To evaluate complete and partial response rate of preoperative radiation and cetuximab in patients with esophageal and GE junction carcinomas		36 months	No
Secondary	To evaluate time to relief of dysphagia in patients with esophageal and GE junction carcinomas receiving preoperative radiation and cetuximab		36 months	No
Secondary	To evaluate the overall toxicities of preoperative radiation and cetuximab in patients with esophageal and GE junction carcinomas		36 months	Yes
Secondary	To perform exploratory molecular correlates to determine the mechanisms of response and resistance to cetuximab and radiation therapy.		36 months	No

External Links

•   Hoosier Oncology Group Home Page