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Genetic Analysis-Guided Irinotecan Hydrochloride Dosing of gFOLFIRINOX in Treating Patients with Locally Advanced Gastroesophageal or Stomach Cancer

Trial Status: Active

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.

Inclusion Criteria

  • Histologically confirmed locally advanced gastric (primary endpoint includes proximal and mid-body stomach) or esophagogastric adenocarcinoma; distal gastric (antral) adenocarcinomas are eligible for enrollment but will not be included in the primary analysis
  • Locally advanced disease as determined by endoscopic ultrasound (EUS) stage >= primary tumor (T) 3 and/or any T, lymph nodes (N)+ disease without metastatic disease (Mx)
  • HER2+ and HER2- patients are eligible
  • Cardiac ejection fraction >= 50% (for HER2+ patients) as assessed by echocardiogram, multi gated acquisition scan (MUGA) scan, or cardiac magnetic resonance imaging (MRI)
  • All patients must have diagnostic laparoscopy with diagnostic washings for cytology; both cytology positive and negative patients are eligible for enrollment, but only cytology negative patients will be included in the primary analyses; gross peritoneal disease is not eligible
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1
  • Eligible for surgery with curative intent
  • Absolute neutrophil count (ANC) >= 1250/ul
  • Hemoglobin >= 9 g/dL
  • Platelets >= 100,000/ul
  • Total bilirubin < 1.5 x upper limit of normal
  • Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) < 2.5 x upper limit of normal
  • Creatinine =< 1.5 x upper limit of normal
  • Measurable or non-measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 will be allowed
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation, up until 30 days after final study treatment; should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately
  • Patients taking substrates, inhibitors, or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) should be encouraged to switch to alternative drugs whenever possible, given the potential for drug-drug interactions with irinotecan
  • Signed informed consent

Exclusion Criteria

  • Previous or concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or any other cancer for which the patient has been previously treated and the lifetime recurrence risk is less than 30%
  • Inflammatory bowel disease that is uncontrolled or on active treatment (Crohn’s disease, ulcerative colitis)
  • Diarrhea, grade 1 or greater by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version [v] 4.0)
  • Neuropathy, grade 2 or greater by NCI-CTCAE, v 4.0
  • Serious underlying medical or psychiatric illnesses that would, in the opinion of the treating physician, substantially increase the risk for complications related to treatment
  • Active uncontrolled bleeding
  • Pregnancy or breastfeeding
  • Major surgery within 4 weeks


University of Chicago Comprehensive Cancer Center
Status: ACTIVE
Contact: Daniel Virgil Thomas Catenacci
Phone: 773-702-7596
NorthShore University HealthSystem
Contact: Mark S. Talamonti
Phone: 847-570-2560
NorthShore University HealthSystem-Evanston Hospital
Contact: Robert de Wilton Marsh
Phone: 847-570-2112
Ingalls Memorial Hospital
Status: ACTIVE
Contact: Mark Farrell Kozloff
Phone: 708-915-6119


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.


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.


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 46 hours continuously 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 46 hours continuously, 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 also undergo collection of blood samples before and after neoadjuvant therapy, after surgery, at post-adjuvant therapy, and if cancer recurs.

After completion of study treatment, patients are followed up every 3 months for 1-2 years and then every 6 months for 3-5 years.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
University of Chicago Comprehensive Cancer Center

Principal Investigator
Daniel Virgil Thomas Catenacci

  • Primary ID IRB14-0594
  • Secondary IDs NCI-2014-02574
  • ID NCT02366819