This pilot phase I trial studies genetic analysis-guided irinotecan hydrochloride dosing of genotype-directed fluorouracil, irinotecan hydrochloride, leucovorin, oxaliplatin (gFOLFIRINOX) with or without trastuzumab in treating patients with gastroesophageal or stomach cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced). Drugs used in chemotherapy, such as fluorouracil, irinotecan hydrochloride, leucovorin, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Leucovorin may also help fluorouracil work better. Trastuzumab binds to human epidermal growth factor 2 (HER2) on the surface of HER2-positive cancer cells, and may kill tumor cells. Genetic analysis may help doctors determine what dose of irinotecan hydrochloride patients can tolerate.
Additional locations may be listed on ClinicalTrials.gov for NCT02366819.
Locations matching your search criteria
United States
Illinois
Chicago
University of Chicago Comprehensive Cancer CenterStatus: Temporarily closed to accrual
Contact: Ardaman Shergill
Phone: 773-702-4274
Harvey
Ingalls Memorial HospitalStatus: Temporarily closed to accrual
Contact: Mark Farrell Kozloff
Phone: 708-915-6119
PRIMARY OBJECTIVES:
I. To determine the residual tumor (R) 0 resection rate.
II. To determine the pathologic complete response (pCR) rate of up to 36 patients treated with 4 cycles of neoadjuvant gFOLFIRINOX (and trastuzumab for HER2 positive [+] gastroesophageal adenocarcinoma [GEC]) (UGTA1A1 genotype-dosed irinotecan [irinotecan hydrochloride]) regimen.
SECONDARY OBJECTIVES:
I. Response rate (radiographic [computed tomography (CT)], and metabolic (positron emission tomography [PET] maximum standardized uptake value [SUVmax]) to chemotherapy.
II. Chemotherapy-related toxicity.
III. Surgical morbidity.
IV. Overall survival (OS) measured from the time of histologic diagnosis.
V. Disease-free survival measured from the time of histologic diagnosis.
VI. Pattern of recurrence (distant, locoregional, both).
VII. HER2+ versus (vs) HER2 negative (-) difference in clinical outcomes.
OUTLINE:
PREOPERATIVE THERAPY: Patients receive oxaliplatin intravenously (IV) over 2 hours, irinotecan hydrochloride IV over 90 minutes, fluorouracil IV over 46 hours continuously, and leucovorin IV over 2 hours on day 1. Patients who are HER2+ also receive trastuzumab IV over 30-90 minutes on day 1. Cycles repeat every 2 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity.
SURGERY: Patients undergo surgery.
POST-OPERATIVE THERAPY: Beginning 5-10 weeks after surgery, patients receive oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, fluorouracil IV over 46 hours continuously, leucovorin IV over 2 hours, and trastuzumab IV over 30-90 minutes (HER2+ patients only) on day 1. Cycles repeat every 2 weeks for 4 more cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo collection of blood samples before and after neoadjuvant therapy, after surgery, at post-adjuvant therapy, and if cancer recurs. Patients also undergo computed tomography (CT), CT/positron emission tomography (PET), and upper endoscopy throughout the trial, and HER2+ patients also undergo multigated acquisition scans (MUGA) or echocardiograms (ECHO) throughout the trial. Additionally, patients may undergo laparoscopies and endoscopic ultrasounds (EUS) as clinically indicated throughout the study.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3-5 years.
Lead OrganizationUniversity of Chicago Comprehensive Cancer Center
Principal InvestigatorArdaman Shergill
