Protocol Title:

A Phase I/II Study of Low-Dose Upper Abdominal Radiation Thearpy (UART) or Whole (W) Art as Chemosensitizer in Patients with Locally Advanced or Metastatic Tumors of the Gastrointestinal Tract or Ovary

Protocol Status:

Pending

Protocol Number:

J-0727

Type of Cancer:

Locally Advanced Metastatic Tumors of the Gastrointestinal Tract or Ovary

Principal Investigator:

Joseph Herman, M.D.

Research Nurse:

Beth Griffith, R.N.

Phase Number:

I/II

General Eligibility:

Men or women can participate if they are 18 years of age or older as well as having either locally advanced or metastatic tumors of the gastrointestinal tract or ovary. Patients must have adequate hemetologic, hepatic, and renal function. Subjects can have had previous malignancies along with brain metastasis but only under certain specific situations.

Purpose:

To assess the maximum tolerated dose of low-dose UART or WART given in combination with standard fixed dose-rate Gemcitabine in patients with advanced GI or ovarian tumors ( Phase I ).

To assess response rate and survival in advanced upper GI tumors following completion of therapy (Phase II ).

Treatment:

Chemotherapy: Gemcitabine will be given at 1250 mg per meter squared over 2 hours days 1 and 8 of a 21 day cycle for a total of 4 cycles. Low-dose WART or UART: Patients and treatment will be stratified according to whether they have A) locally advanced carcinomas with unassociated clinical evidence of diffuse peritoneal carcinomatosis or B) peritoneal carcinomatosis. Those with locally advanced disease unassociated with peritoneal carcinomatosis will be treated with UART while those with peritoneal carcinomatosis will be treated with WART. WART will be as standard with AP/PA treatment fields encompassing the whole of the peritoneal surface from the level of the diaphragm to the obturator foramen. AP/PA kidney blocks will be used at a dose of 20 Gy and APPA shielding of 30-50% of the liver will be used at 22Gy. UART will differ from WART in that the lower field edge will be limited to the top of the iliac crest. Radiation therapy will be given on the days of and the day after each administration of Gemcitabine. Treatment will be given in 2 fractions with a minimum 4 hr inter-fraction interval. The first fraction of radiotherapy will be given after the initiation of Gemcitabine. A classic phase I dose escalation design will be used with the initial radiation dose per fraction being 60 cGy. A maximum of 3-6 patients at each of 4 possible WART or UART dose levels/bins will be evaluated (i.e. 60, 70, 80, or 90 cGy bid). Dose escalation bins will be stratified according to whether UART 6 or WART is used. If dose limiting toxicity (DLT) is not experienced, with DLT defined as Grade 4 neutropenia or thrombocytopenia, neutropenic fever, or Grade 3 or greater nonhematologic (except nausea, vomiting, hyperbilirubinemia secondary to biliary obstruction, and any grade of alopecia), the dose of UART or WART will be escalated by 10 cGy per fraction for the next cohort of 3-6patients. A minimum of 3 patients within each cohort who are at least 4 weeks into protocol Rx is required prior to proceeding with dose escalation. Note: Grade 4 neutropenia has to last at least 5 days or be associated with fever to be considered a dose limiting toxicity. After DLT is identified an additional 3 patients will be accrued. If only 1 of 6 patients experiences DLT, then dose escalation will continue with each subsequent dose level requiring 6 patients, until a maximum of 2 of 6 patients experiences DLT (i.e. MTD) or a maximum total UART or WART dose of 2880 cGy (i.e. 90 cGy per fraction) has been evaluated.