Overview

This trial is active, not recruiting.

Conditions adenocarcinoma of the gastroesophageal junction, esophageal cancer, gastric cancer
Treatments folfox regimen, docetaxel, fluorouracil, irinotecan hydrochloride, leucovorin calcium, oxaliplatin
Phase phase 2
Sponsor Southwest Oncology Group
Collaborator National Cancer Institute (NCI)
Start date February 2012
End date March 2018
Trial size 213 participants
Trial identifier NCT01498289, NCI-2012-00096, S1201, U10CA032102

Summary

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, leucovorin calcium, fluorouracil, irinotecan hydrochloride, and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Combining more than one drug may kill more tumor cells. It is not yet known which regimen of combination chemotherapy is more effective in treating tumor cells.

PURPOSE: This randomized phase II trial studies how well oxaliplatin, leucovorin calcium, and fluorouracil work compared to irinotecan hydrochloride and docetaxel in treating patients with esophageal cancer, gastric cancer, or gastroesophageal junction cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
FOLFOX regimen: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
folfox regimen
Given IV. Fluorouracil, oxaliplatin, & leucovorin calcium.
fluorouracil 5-fluorouracil
400 mg/m^2, IV bolus on Day 1 of each 14 day cycle; 2400 mg/m^2 IV over 46-48 hours on Days 1-2 of each 14 day cycle.
leucovorin calcium NSC-3590
400 mg/m^2, IV over 2 hours on Day 1 of every 14 day cycle.
oxaliplatin Eloxatin
85 mg/m^2, IV over 2 hours on Day 1 of every 14 day cycle.
(Experimental)
Patients receive irinotecan hydrochloride IV over 90 minutes and docetaxel IV over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
docetaxel Taxotere
30 mg/m^2, IV over 30 minutes on Day 1,8 of each 21 day cycle.
irinotecan hydrochloride CPT-11
65 mg/m^2, IV over 90 minutes on Days 1 & 8 of every 21 day cycle.

Primary Outcomes

Measure
Progression-free survival (PFS) between high-ERCC1 and low-ERCC1 patients treated with FOLFOX versus irinotecan hydrochloride plus docetaxel
time frame: Up to 3 years
PFS between low-ERCC1 and high-ERCC1 patients treated with FOLFOX
time frame: Up to 3 years
PFS between low-ERCC1 and high-ERCC1 patients treated with irinotecan hydrochloride plus docetaxel
time frame: Up to 3 years

Secondary Outcomes

Measure
Overall survival
time frame: Up to 3 years
Response rate
time frame: Up to 3 years
Toxicity
time frame: Up to 3 years

Eligibility Criteria

Male or female participants from 18 years up to 120 years old.

DISEASE CHARACTERISTICS: - Patients must have unresectable advanced or metastatic histologically or cytologically confirmed adenocarcinoma of the esophagus, stomach, or gastroesophageal junction (GEJ) - Patients must not have received treatment for metastatic or unresectable disease - Patients must not have brain metastases - Patients must have measurable and/or non-measurable disease - Patients who have had HER-2 expression testing prior to patient consent to this study must be HER-2 negative; if HER-2 expression has not been tested prior to patient consent to this study, a second specimen must be submitted for HER-2 expression; if the specimen is HER-2 positive (or if HER-2 could not be evaluated), the patient will not be randomized - Patients must have completed any prior neoadjuvant and adjuvant therapy for resectable disease at least 180 days prior to registration PATIENT CHARACTERISTICS: - Zubrod performance status of 0-1 - Hemoglobin ≥ 9 g/dL - Absolute neutrophil count (ANC) ≥ 1,500/mcL - Platelets ≥ 100,000/mcL - Total bilirubin ≤ 1.5 mg/dL regardless of whether patients have liver involvement secondary to tumor - AST and ALT both ≤ 3 times institutional upper limit of normal (IULN) unless the liver is involved with tumor, in which case both AST and ALT must be ≤ 5 times IULN - Serum creatinine < 1.5 mg/dL within 28 days prior to registration AND/OR calculated creatinine clearance > 60 mL/min - Patients must not have motor or sensory neuropathy > Grade 1 using CTCAE version 4.0 - Patients must not be pregnant or nursing; women and men of reproductive potential must have agreed to use an effective contraceptive method - No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for five years PRIOR CONCURRENT THERAPY: - See Disease Characteristics - All palliative radiation therapy alone must be completed at least 14 days prior to registration - Patient must have no plans to receive concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or any other type of therapy for treatment of cancer while on this protocol treatment

Additional Information

Official title A Randomized Phase II Pilot Study Prospectively Evaluating Treatment for Patients Based on ERCC1(Excision Repair Cross-Complementing 1) for Advanced/Metastatic Esophageal, Gastric or Gastroesophageal Junction (GEJ) Cancer
Principal investigator Syma Iqbal, MD
Description OBJECTIVES: - To assess progression-free survival of high-excision repair cross-complementing 1(ERCC1) patients with advanced or metastatic cancer of the esophagus, stomach, or gastroesophageal junction (GEJ) treated with FOLFOX comprising oxaliplatin, leucovorin calcium, and fluorouracil compared to those treated with irinotecan hydrochloride plus docetaxel. - To assess progression-free survival of low-ERCC1 patients with advanced or metastatic cancer of the esophagus, stomach, or GEJ treated with FOLFOX compared to those treated with irinotecan hydrochloride plus docetaxel. - To assess progression-free survival of low-ERCC1 patients with advanced or metastatic cancer of the esophagus, stomach, or GEJ treated with FOLFOX compared to high-ERCC1 patients treated with FOLFOX. - To assess overall survival of and toxicities in each of the two treatment arms in this group of patients. - To assess the response probability (confirmed and unconfirmed, complete and partial responses) in the subset of patients with measurable disease in each of the two treatment arms. - To explore whether there is evidence of interaction between treatment arm and ERCC1 expression in this group of patients. (Exploratory) - To bank tissue and blood for future translational medicine studies; a) To explore the relationship of ERCC-1 and ERCC-2 single nucleotide polymorphism (SNP) genotypes with clinical outcome in these patients; and b) To explore the association between germline variations in these SNPs and ERCC-1 mRNA expression in these patients. (Exploratory) OUTLINE: This is a multicenter study. Patients are stratified according to ERCC1 expression (high [≥ 1.7] vs low [< 1.7]), and disease site (esophageal vs gastric/gastroesophageal junction). Patients are randomized to 1 of 2 treatment arms. - Arm I (FOLFOX): Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1-2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. - Arm II: Patients receive irinotecan hydrochloride IV over 90 minutes and docetaxel IV over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Blood and tumor tissue samples may be collected for ERCC1 expression analysis and future research studies. After completion of study treatment, patients are followed up every 3 months for up to 3 years.
Trial information was received from ClinicalTrials.gov and was last updated in May 2016.
Information provided to ClinicalTrials.gov by Southwest Oncology Group.