View Cancer Clinical Trials

Details

Title A Phase II Trial of modified FOLFOX-6 Induction Chemotherapy followed by Esophagectomy and post-operative response based chemoradiotherapy in patients with locoregionally advanced adenocarcinoma of the esophagus, gastro-esophageal junction, and gastric cardia.

IRB CASE6213

CC 13-1422

Hospital Fairview, Hillcrest, Main Campus, Mansfield, North Coast Cancer, Strongsville, Wooster

Disease Esophageal, Gastroesophageal junction (GEJ), GI (Gastrointestinal), Head and Neck

Drug Folfox

Description

1. To assess the ability of response adapted adjuvant chemoradiotherapy to improve the 1 year RFS compared to historical data in patients with >50% remaining viable tumor after induction chemotherapy.

1. To determine the rates of symptomatic, endoscopic, and pathologic response to induction chemotherapy.
2. To determine the rate of R0 resection after induction chemotherapy.
3. To establish the toxicity profile of this tri-modality regimen.
4. To assess the recurrence free survival (RFS) and overall survival (OS) of this trimodality therapy regimen for the entire cohort and in patients who do and do not achieve a pathologic response.
5. To assess patterns of failure and assess the rates of distant metastatic control (DMC) and locoregional control (LRC) of this tri-modality therapy regimen.

Inclusion Criteria

1. Patients must have a histologic diagnosis of adenocarcinoma of the esophagus, GEJ, or GC based on biopsy material or adequate cytologic exam. Tumors of the GC are defined as originating within 5 cm of the GEJ.
2. Patients must be clinically staged according to the 7th edition (2010) of the AJCC staging system and must have either clinical T3-4a, or ≥ N1 disease. Staging should include upper endoscopy with endoscopic ultrasound and a FDG-PET/CT scan (with diagnostic CT abdomen/pelvis preferred).
3. Patients must have an ECOG performance status of 0-1.
4. Patients must have adequate bone marrow function as evidenced by:
   1. Absolute neutrophil count ≥ 1,500/ml.
   2. Platelet count ≥ 100,000/ml.
5. Patients must have adequate renal function as evidenced by: Serum creatinine (Scr) ≤ 1.5mg/dl. If the Scr > 1.5, patients may still be eligible if the calculated GFR (Cockroft-Gault) is ≥ 40ml/minute.
6. Patients must have adequate hepatic function as evidenced by:
   1. Serum total bilirubin ≤ 1.5X the institutional ULN.
   2. Alkaline phosphatase ≤ 3X the institutional ULN.
   3. AST/ALT ≤ 3X the institutional ULN.
   4. Patients with Gilberts syndrome are eligible provided the total bilirubin is ≤ 3 and the remainder of the liver function tests (ALT, AST, ALK Phos) are within the institutional normal range.
7. Patients must have a FEV-1 and DLCO > 50% predicted.
8. Patients or their legal representatives must be able to read, understand, provide and sign informed consent to participate in the trial.
9. Patients of childbearing potential must agree to use an effective form of contraception during this study and for 90 days following the last dose of chemotherapy. An effective form of contraception is an oral contraceptive or a double barrier method.
10. Age ≥ 18 years

Exclusion Criteria

1. Patients with any other diagnosis except for adenocarcinoma (squamous cell carcinoma, small cell carcinoma, mixed adenosquamous, lymphoma, sarcoma, etc.) will be ineligible.
2. Patients with evidence of clinical T4b (unresectable) or M1 (distant metastasis) according to the AJCC 2010 staging system will be ineligible.
3. No prior chemotherapy, radiation therapy, or surgery for this malignancy will be allowed. Prior endoscopic procedures for superficial disease (endoscopic mucosal resection, cryotherapy, photodynamic therapy, etc.) will not exclude a patient. Prior dilatation is also allowed.
4. Patients with another active malignancy will not be eligible except for:
   1. Resected basal cell carcinoma and squamous cell carcinoma of the skin, cervical or prostatic intraepithelial neoplasia, and ductal or lobular carcinoma in situ of the breast.
   2. Patients with localized prostate cancer who have received curative intent therapy are also eligible provided:
      1. Surgically treated patients have an undetectable PSA.
      2. Patients treated with brachytherapy have a PSA within the institutional normal range.
      3. Patients who have received pelvic external beam radiotherapy are not eligible.
5. Patients with a clinically apparent active infection will not be eligible (Please note, an isolated elevation in the white blood cell count, by itself, does not constitute evidence of an infection).
6. Patients with known hypersensitivity to any component of the chemotherapy regimen will not be eligible.
7. Patients with a baseline peripheral neuropathy ≥ grade 2 will not be eligible.
8. Patients who are receiving any other concurrent investigational therapy, or who have received investigational therapy within 30 days of the first scheduled day of protocol treatment (investigational therapy as defined as treatment for which there is currently no regulatory authority approved indication) will not be eligible.
9. Patients who are pregnant or lactating will not be eligible. Pregnant patients are ineligible due to the potential teratogenic effects of cytotoxic chemotherapy and radiotherapy.
10. Patients with angina, a cardiac ejection fraction < 50%, or ischemic heart disease are not eligible.
11. Patients with any other medical condition, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with the patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results, will not be eligible.
12. Patients with any history of solid organ or bone marrow transplant will not be eligible.
13. Patients with a known history of infection with hepatitis B or hepatitis C virus (active, previously treated, or both) will not be eligible due to the increased risk of hepatotoxicity and viral reactivation associated with systemic chemotherapy.
14. Patients with known infection with HIV will not be eligible. HIV infected patients are ineligible because of the increased risk for lethal infections when treated with marrow suppressive therapy.