S1201: Combination Chemo for Patients W/Advanced or Metastatic Esophageal, Gastric, or Gastroesophageal Junction Cancer
- Conditions
- Esophageal CancerAdenocarcinoma of the Gastroesophageal JunctionGastric Cancer
- Interventions
- Registration Number
- NCT01498289
- Lead Sponsor
- SWOG Cancer Research Network
- Brief 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.
- Detailed 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 213
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm I leucovorin calcium 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. Arm I FOLFOX regimen 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. Arm I fluorouracil 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. Arm II docetaxel 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. Arm I oxaliplatin 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. Arm II irinotecan hydrochloride 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.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) Up to 3 years after registration OS is the length of time between protocol registration and patient death
Progression-free Survival (PFS) in High-ERCC1 Patients Up to 3 years after registration Progression-free survival is the length of time between protocol registration and disease progression or death, whichever occurs first.
PFS in Low-ERCC1 Participants Up to 3 years after registration Progression-free survival is the length of time between protocol registration and disease progression or death, whichever occurs first.
- Secondary Outcome Measures
Name Time Method PFS Variation by ERCC1 up to 3 years after registration Progression-free survival is the length of time between protocol registration and disease progression or death, whichever occurs first.
Participants were divided into subgroups according to ERCC1 quartiles to assess whether the differences in PFS between the two treatment arms varied by ERCC1 levels.Overall Response Rate (ORR) Up to 3 years after registration ORR (complete response, unconfirmed complete response, partial response, unconfirmed partial response) in patients with measurable disease were assessed in each arm and compared between arms using Chi-squared test.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs Duration of treatment and follow up until death or 3 years post registration Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Related Research Topics
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Trial Locations
- Locations (504)
University of South Alabama Mitchell Cancer Institute
🇺🇸Mobile, Alabama, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Sutter Auburn Faith Hospital
🇺🇸Auburn, California, United States
Alta Bates Summit Medical Center-Herrick Campus
🇺🇸Berkeley, California, United States
Mills - Peninsula Hospitals
🇺🇸Burlingame, California, United States
Sutter Davis Hospital
🇺🇸Davis, California, United States
Los Angeles County-USC Medical Center
🇺🇸Los Angeles, California, United States
University of Southern California/Norris Cancer Center
🇺🇸Los Angeles, California, United States
Fremont - Rideout Cancer Center
🇺🇸Marysville, California, United States
Memorial Medical Center
🇺🇸Springfield, Illinois, United States
Scroll for more (494 remaining)University of South Alabama Mitchell Cancer Institute🇺🇸Mobile, Alabama, United States