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

NCT ID: NCT02366819

Last Updated: 2025-06-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-12-11

Study Completion Date

2026-06-08

Brief Summary

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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.

Detailed Description

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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 mFOLFIRINOX (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. Human epidermal growth factor receptor 2 positive (HER2+) vs HER2 negative (-) difference in clinical outcomes.

OUTLINE:

PREOPERATIVE THERAPY: Patients receive oxaliplatin intravenously (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 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.

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

Conditions

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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (mFOLFIRINOX, surgery)

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.

Group Type EXPERIMENTAL

Oxaliplatin

Intervention Type DRUG

Given IV

Leucovorin Calcium

Intervention Type DRUG

Given IV

Irinotecan Hydrochloride

Intervention Type DRUG

Given IV

Fluorouracil

Intervention Type DRUG

Given IV

Conventional Surgery

Intervention Type PROCEDURE

Undergo surgery

Interventions

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Oxaliplatin

Given IV

Intervention Type DRUG

Leucovorin Calcium

Given IV

Intervention Type DRUG

Irinotecan Hydrochloride

Given IV

Intervention Type DRUG

Fluorouracil

Given IV

Intervention Type DRUG

Conventional Surgery

Undergo surgery

Intervention Type PROCEDURE

Other Intervention Names

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CF surgery, conventional

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

University of Chicago

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Daniel Catenacci

Role: PRINCIPAL_INVESTIGATOR

University of Chicago Comprehensive Cancer Center

Locations

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University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status RECRUITING

Kellogg Cancer Center - Evanston Hospital

Evanston, Illinois, United States

Site Status RECRUITING

NorthShore University HealthSystem

Evanston, Illinois, United States

Site Status RECRUITING

Countries

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United States

Facility Contacts

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Daniel V. Catenacci

Role: primary

773-702-7596

Robert d. Marsh

Role: primary

847-570-2112

Mark S. Talamonti

Role: primary

847-570-2560

References

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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.

Reference Type DERIVED
PMID: 32058557 (View on PubMed)

Other Identifiers

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NCI-2014-02574

Identifier Type: REGISTRY

Identifier Source: secondary_id

IRB14-0594

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA014599

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB14-0594

Identifier Type: -

Identifier Source: org_study_id

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