Clinical trial NCT00319735: Cetuximab and Radiation Therapy for Surgically Resectable Esophageal and Gastroesophageal (GE) Junction Carcinomas
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Esophageal Cancer
Lead sponsor: Hoosier Cancer Research Network
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
name: Walther Cancer Institute
First posted: 2006-04-27
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Complete Pathologic Response (pCR)
timeFrame: 36 months
Secondary outcomes:
measure: Complete Pathological Response Rate for Patients Who Underwent Esophagectomy.
timeFrame: Up to 36 months
measure: Time to Relief of Dysphagia
timeFrame: 36 months
measure: Evaluate Toxicity
timeFrame: 36 months
measure: Perform Exploratory Molecular Correlates.
timeFrame: 36 months
measure: Complete and Partial Response Rate for Patients by Disease Stage: IIA
timeFrame: 36 months
measure: Complete and Partial Response Rate for Patients by Disease Stage: IIB
timeFrame: 36 months
measure: Complete and Partial Response Rate for Patients by Disease Stage: III
timeFrame: 36 months
measure: Complete and Partial Response Rate for Patients by Histology: Adenocarcinoma
timeFrame: 36 months
measure: Complete and Partial Response Rate for Patients by Histology: Squamous Cell
timeFrame: 36 months
Other outcomes:
Locations:
city: Galesburg
country: United States
facility: Medical & Surgical Specialists, LLC
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Indianapolis
country: United States
facility: Community Regional Cancer Center
state: Indiana
city: Terre Haute
country: United States
facility: AP&S Clinic
state: Indiana
city: St. Louis
country: United States
facility: Siteman Cancer Center
state: Missouri
city: Dallas
country: United States
facility: Texas Oncology, PA
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
Study officials:
affiliation: Hoosier Oncology Group, LLC
name: Carlos Becerra, M.D.
role: STUDY_CHAIR
affiliation: Hoosier Oncology Group, LLC
name: Nasser Hanna, M.D.
role: STUDY_CHAIR
References:
citation: 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.