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

Launched by UNIVERSITY OF CHICAGO · Feb 11, 2015

Keywords

ClinConnect Summary

This clinical trial is exploring a new way to give chemotherapy to patients with advanced stomach or esophageal cancer. The study focuses on using genetic testing to help doctors figure out the best dose of a specific chemotherapy drug called irinotecan hydrochloride, which is part of a treatment regimen known as mFOLFIRINOX. This regimen combines several drugs that work together to stop cancer cells from growing and spreading. By tailoring the dose based on genetic analysis, the researchers hope to improve treatment outcomes and make the process safer for patients.

To be eligible for the trial, participants should have a confirmed diagnosis of locally advanced gastric or esophagogastric cancer and must be able to undergo surgery aimed at curing the disease. They should also be generally healthy, with specific blood counts and liver function within normal ranges. Patients aged 65 and older are welcome to join, and both men and women can participate, provided they agree to use effective contraception during the study. Participants can expect to receive close monitoring and care throughout the trial, and they will be contributing to important research that could help improve cancer treatment in the future.

Gender

ALL

Eligibility criteria

• 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 enrolment 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)
• • All patients must have diagnostic laparoscopy with diagnostic washings for cytology; both cytology positive and negative patients are eligible for enrolment, 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 for patients without liver metastases OR SGOT and SGPT \< 5 x upper limit of normal for patients with liver metastases
• • Creatinine =\< 1.5 x upper limit of normal
• • Measurable or non-measurable disease by Response Evaluation Criteria in Solid Tumor (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
• • Patients with any polymorphism in UGT1A1 other than \*1 or \*28 (e.g, \*6) will be allowed and treated as in the \*28/\*28 dosing group