RTOG 1010 - A PHASE III TRIAL EVALUATING THE ADDITION OF TRASTUZUMAB TO TRIMODALITY TREATMENT OF HER2-OVEREXPRESSING ESOPHAGEAL ADENOCARCINOMA
Description
RTOG 1010 - A PHASE III TRIAL EVALUATING THE ADDITION OF TRASTUZUMAB TO TRIMODALITY TREATMENT OF HER2-OVEREXPRESSING ESOPHAGEAL ADENOCARCINOMA
Primary:
To determine if trastuzumab increases disease-free survival when combined with trimodality treatment (radiation plus chemotherapy followed by surgery) for patients with HER2- overexpressing esophageal adenocarcinoma
Secondary:
To evaluate whether the addition of trastuzumab to this neoadjuvant chemoradiation increases the pathologic complete response rate and overall survival of these patients.
To develop a tissue bank of tumor tissue from patients with non-metastatic esophageal adenocarcinoma.
To determine molecular correlates of complete pathologic response, disease-free survival, and overall survival of patients treated with these regimens.
To evaluate predictors of cardiotoxicity in patients treated with these regimens.
To evaluate adverse events associated with these regimens in these patients.
Tertiary Quality of Life Objectives
To determine whether trastuzumab improves patient-reported Functional Assessment of Cancer Therapy for Esophageal Cancer (FACT-E), Esophageal Cancer Subscale (ECS) score.
To determine whether an improvement in the FACT-E ECS score at 6-8 weeks after completion of neoadjuvant chemoradiation correlates with pathologic complete response.
To determine whether pathologic complete response correlates with the FACT-E ECS score at 1 year and/or 2 years in patients treated with these regimens.
To determine whether the addition of trastuzumab to neoadjuvant chemoradiation improves the Swallow Index and Eating Index Subscale scores of the FACT-E of these patients.
To determine whether the addition of trastuzumab to neoadjuvant chemoradiation impacts quality-adjusted survival of these patients.
Study/Treatment
GI Tract Cancer
Inclusion/Notes
Eligibility Criteria:
PRIOR TO STEP 1 REGISTRATION BUT WITHIN 56 DAYS
PRIOR TO STEP 2 REGISTRATION
Age = 18
Pathologically confirmed primary adenocarcinoma of the esophagus that involves the mid (up to 25 cm), distal, or esophagogastric junction. The cancer may involve the stomach up to 5 cm
Endoscopy with biopsy
Intent to submit tissue for central HER2 testing
Stage T1N1-2, T2-3N0-2, according to the American Joint Committee on Cancer (AJCC) 7th edition staging, based upon the following minimum diagnostic work-up:
Chest/abdominal/pelvic CT or whole-body PET/CT (NOTE: if CT is performed at this time point whole-body PET/CT will be required prior to Step 2 registration)
Patients may have regional adenopathy including para-esophageal, gastric,gastrohepatic and celiac nodes. If celiac adenopathy is present, it must be < 2 cm.
Patients with tumors at the level of the carina or above must undergo bronchoscopy to exclude fistula
Zubrod performance status 0-2
CBC/differential obtained, with adequate bone marrow function defined as follows:
Absolute neutrophil count (ANC) = 1,500 cells/mm3
Platelets = 100,000 cells/mm3
Hemoglobin = 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb = 8.0 g/dl is acceptable)
Additional laboratory studies
Creatinine = 2 x the upper limit of normal
Bilirubin = 1.5 x upper limit of normal
AST = 3 x upper limit of normal
For women of childbearing potential, a negative serum or urine pregnancy test
Patients must sign study-specific informed consent prior to study entry
Conditions for Patient Eligibility PRIOR TO STEP 2 REGISTRATION (HER2-positive patients only)
HER2 expressing adenocarcinoma of the esophagus centrally assessed within 56 days prior to Step 2 registration
Surgical consultation to confirm that patient will be able to undergo curative resection after completion of chemoradiation within 56 days prior to Step 2 registration
Radiation oncology consultation to confirm that disease can be encompassed in a radiotherapy field within 56 days prior to Step 2 registration
Consultation with a medical oncologist within 56 days prior to Step 2 registration
Stage T1N1-2, T2-3N0-2, according to the AJCC 7th edition staging, based upon the following minimum diagnostic work-up:
History/physical examination, with documentation of the patient’s weight, within 14 days prior to Step 2 registration
Whole-body PET/CT scan within 56 days prior to Step 2 registration (if only CT performed prior to Step 1 registration)
Endoscopic ultrasound within 56 days prior to Step 2 registration, unless the patient is found to have adenopathy per CT or whole-body PET/CT scan
EKG within 56 days prior to Step 2 registration
Serum creatinine = 2 x the upper limit of normal within 14 days prior to step 2 registration
Zubrod performance status 0-2 within 14 days prior to Step 2 registration
For women of childbearing potential, a negative serum pregnancy test within 14 days prior to Step 2 registration
LVEF = institutional lower limit of normal by cardiac echo or MUGA scan within 56 days prior to Step 2 registration
Women of childbearing potential and sexually active male participants must agree to practice adequate contraception while on study and for at least 60 days following the last dose of chemotherapy or trastuzumab
Exclusions
Patients with cervical esophageal carcinoma
Patients with T1N0 disease, T4 disease, and proximal esophageal cancers (15-24 cm)
Prior systemic chemotherapy for esophageal cancer; note that prior chemotherapy for a different cancer is allowable
Prior radiation for esophageal cancer or prior chest radiotherapy
Prior anthracycline or taxane
Evidence of tracheoesophageal fistula or invasion into the trachea or major bronchi
Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 2 years (e.g., carcinoma in situ of the breast, oral cavity, or cervix are permissible)
Medical contraindications to esophagectomy
Prior therapy with any agent targeting the HER2 pathway or HER1 (EGFR)pathway
Prior therapy with trastuzumab
Prior allergic reaction to the study drugs involved in this protocol or to a monoclonal antibody
Previous history of congestive heart failure
Severe, active comorbidity, defined as follows:
Unstable angina in the last 6 months
Transmural myocardial infarction within the last 6 months
Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
Acquired immune deficiency syndrome (AIDS) based upon current CDC definition; note, however, that HIV testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immunocompromised patients.
Pregnant or nursing women or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.
Start Date
03/15/2011
Principal Name
John A. Pablo, M.D.
Contact Name
Nancy N. and J.C. Lewis Cancer & Research Pavilion
Fax
(912) 819-5705
Phone
(912) 819-5704
Nancy N. and J.C. Lewis Cancer & Research Pavilion225 Candler Drive, Savannah, Georgia 31405
