Clinical trial NCT02366819: Genetic Analysis-Guided Irinotecan Hydrochloride Dosing of mFOLFIRINOX in Treating Patients With Locally Advanced Gastroesophageal or Stomach Cancer
Official title: PERIOP-FOLFIRINOX: A Pilot Trial of Perioperative Genotype-guided Irinotecan Dosing of gFOLFIRINOX for Locally Advanced Gastroesophageal Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: 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
Lead sponsor: University of Chicago
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2015-02-19
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: 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.

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

Primary outcomes:
measure: R0 (analysis will be performed evaluating the R0 rate)
timeFrame: During surgery
Secondary outcomes:
measure: Response rate
timeFrame: Up to 5 years
measure: Surgical morbidity
timeFrame: Up to 5 years
measure: Pattern of recurrence
timeFrame: Up to 5 years
measure: Incidence of toxicity based on NCI-CTCAE v 4.0
timeFrame: Up to 5 years
measure: 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)
timeFrame: Time from enrollment/registration to the time of death, of any cause, assessed up to 5 years
measure: Progression free survival
timeFrame: Time from enrollment/registration to time of progression or death from any cause, assessed up to 5 years
Other outcomes:
measure: Circulating tumor cell (CTC) numbers derived from portal and peripheral blood samples
timeFrame: Up to 5 years
measure: Change in SUVmax for PET/CT studies
timeFrame: Baseline to after 8 weeks of chemotherapy
measure: Change in SUVmax for the primary esophageal tumor
timeFrame: Baseline to up to 5 years
Locations:
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Evanston
country: United States
facility: Kellogg Cancer Center - Evanston Hospital
state: Illinois
city: Evanston
country: United States
facility: NorthShore University HealthSystem
state: Illinois
Study officials:
affiliation: University of Chicago Comprehensive Cancer Center
name: Daniel Catenacci
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.