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

NCT02366819 | Suspended Phase 4

• 3 other identifiers: IRB14-0594NCI-2014-02574P30CA014599
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

Brief Summary

This pilot clinical trial studies genetic analysis-guided irontecan hydrochloride dosing of modified fluorouracil, irinotecan hydrochloride, leucovorin calcium, oxaliplatin (mFOLFIRINOX) in treating patients with gastroesophageal or stomach cancer that has spread from where it started to nearby tissue or lymph nodes. Drugs used in chemotherapy, such as fluorouracil, irinotecan hydrochloride, leucovorin calcium, 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 calcium may also help fluorouracil work better. Genetic analysis may help doctors determine what dose of irinotecan hydrochloride patients can tolerate.

Conditions

Esophageal Adenocarcinoma; Gastric Adenocarcinoma; Stage IIB Gastric Cancer; Stage IIIA Gastric Cancer; Stage IIIB Esophageal Adenocarcinoma; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Adenocarcinoma; Stage IIIC Gastric Cancer; Stage IIIA Esophageal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• R0 (analysis will be performed evaluating the R0 rate)

  Intention-to-treat analysis will be performed, and patients with tumor progression during/after neoadjuvant chemotherapy that precludes surgery will be included as non-R0 resection. A subset analysis will be performed evaluating the R0 rate for those patients actually undergoing surgery.

  During surgery

Secondary Outcomes (6)

• Response rate

  Up to 5 years

• Surgical morbidity

  Up to 5 years

• Pattern of recurrence

  Up to 5 years

• Incidence of toxicity based on NCI-CTCAE v 4.0

  Up to 5 years

• OS (estimated using the Kaplan-Meier procedure and compared in the subgroups of patients with and without pCR (grade 1a) using the log-rank test)

  Time from enrollment/registration to the time of death, of any cause, assessed up to 5 years

Other Outcomes (3)

• Circulating tumor cell (CTC) numbers derived from portal and peripheral blood samples

  Up to 5 years

• Change in SUVmax for PET/CT studies

  Baseline to after 8 weeks of chemotherapy

• Change in SUVmax for the primary esophageal tumor

  Baseline to up to 5 years

Study Arms (1)

Treatment (mFOLFIRINOX, surgery)

EXPERIMENTAL

PREOPERATIVE THERAPY: Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and fluorouracil IV over 46 hours continuously on day 1. Courses repeat every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. SURGERY: Patients undergo conventional surgery. POST-OPERATIVE THERAPY: Beginning 5-10 weeks after surgery, patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, irinotecan hydrochloride IV over 90 minutes, and fluorouracil IV over 46 hours continuously on day 1. Courses repeat every 2 weeks for 4 more courses in the absence of disease progression or unacceptable toxicity.

Drug: Oxaliplatin; Drug: Leucovorin Calcium; Drug: Irinotecan Hydrochloride; Drug: Fluorouracil; Procedure: Conventional Surgery

Interventions

Oxaliplatin DRUG

Given IV

Treatment (mFOLFIRINOX, surgery)

Leucovorin Calcium DRUG

Given IV

Also known as: CF

Treatment (mFOLFIRINOX, surgery)

Irinotecan Hydrochloride DRUG

Given IV

Treatment (mFOLFIRINOX, surgery)

Fluorouracil DRUG

Given IV

Treatment (mFOLFIRINOX, surgery)

Conventional Surgery PROCEDURE

Undergo surgery

Also known as: surgery, conventional

Treatment (mFOLFIRINOX, surgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Chicago: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Kellogg Cancer Center - Evanston Hospital

Evanston, Illinois, 60201, United States

Location

NorthShore University HealthSystem

Evanston, Illinois, 60201, United States

Location

Related Publications (1)

• Catenacci DVT, Chase L, Lomnicki S, Karrison T, de Wilton Marsh R, Rampurwala MM, Narula S, Alpert L, Setia N, Xiao SY, Hart J, Siddiqui UD, Peterson B, Moore K, Kipping-Johnson K, Markevicius U, Gordon B, Allen K, Racette C, Maron SB, Liao CY, Polite BN, Kindler HL, Turaga K, Prachand VN, Roggin KK, Ferguson MK, Posner MC. Evaluation of the Association of Perioperative UGT1A1 Genotype-Dosed gFOLFIRINOX With Margin-Negative Resection Rates and Pathologic Response Grades Among Patients With Locally Advanced Gastroesophageal Adenocarcinoma: A Phase 2 Clinical Trial. JAMA Netw Open. 2020 Feb 5;3(2):e1921290. doi: 10.1001/jamanetworkopen.2019.21290.

  PMID: 32058557 DERIVED

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Stomach Neoplasms

Interventions

Oxaliplatin; Leucovorin; Irinotecan; Fluorouracil; Surgical Procedures, Operative; Congresses as Topic

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Camptothecin; Alkaloids; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Organizations; Health Care Economics and Organizations

Study Officials

• Daniel Catenacci

  University of Chicago Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2015
• First Posted: February 19, 2015
• Study Start: December 11, 2014
• Primary Completion (Estimated): June 8, 2026
• Study Completion (Estimated): June 8, 2026
• Last Updated: March 30, 2026

Record last verified: 2026-03

Locations

US (3)