S1201: Combination Chemo for Patients W/Advanced or Metastatic Esophageal, Gastric, or Gastroesophageal Junction Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Southwest Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT01498289
First received: December 22, 2011
Last updated: July 23, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Adenocarcinoma of the Gastroesophageal Junction
Esophageal Cancer
Gastric Cancer
Drug: FOLFOX regimen
Drug: docetaxel
Drug: fluorouracil
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Drug: oxaliplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • PFS between low-ERCC1 and high-ERCC1 patients treated with FOLFOX [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • PFS between low-ERCC1 and high-ERCC1 patients treated with irinotecan hydrochloride plus docetaxel [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Response rate [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 225
Study Start Date: February 2012
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
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.
Drug: FOLFOX regimen
Given IV. Fluorouracil, oxaliplatin, & leucovorin calcium.
Drug: 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.
Other Names:
  • 5-fluorouracil
  • 5-FU
  • NSC-19893
Drug: leucovorin calcium
400 mg/m^2, IV over 2 hours on Day 1 of every 14 day cycle.
Other Name: NSC-3590
Drug: oxaliplatin
85 mg/m^2, IV over 2 hours on Day 1 of every 14 day cycle.
Other Names:
  • Eloxatin
  • NSC-266046
Experimental: 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.
Drug: docetaxel
30 mg/m^2, IV over 30 minutes on Day 1,8 of each 21 day cycle.
Other Names:
  • Taxotere
  • RP56976
  • NSC-628503
Drug: irinotecan hydrochloride
65 mg/m^2, IV over 90 minutes on Days 1 & 8 of every 21 day cycle.
Other Names:
  • CPT-11
  • NSC-616348

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01498289

Contacts
Contact: Kimberly Kaberle 2106148808 ext 1022 kkaberle@swog.org
Contact: Dana Sparks, MAT 2106148808 ext 1004 dsparks@swog.org

  Show 425 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Principal Investigator: Syma Iqbal, MD University of Southern California
  More Information

Additional Information:
No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT01498289     History of Changes
Other Study ID Numbers: S1201, S1201, U10CA032102, NCI-2012-00096
Study First Received: December 22, 2011
Last Updated: July 23, 2014
Health Authority: United States: Federal Government

Keywords provided by Southwest Oncology Group:
recurrent esophageal cancer
stage IV esophageal cancer
recurrent gastric cancer
stage IV gastric cancer
adenocarcinoma of the gastroesophageal junction
stage IIIB gastric cancer
stage IIIC gastric cancer
stage IIIB esophageal cancer
stage IIIC esophageal cancer
adenocarcinoma of the esophagus
adenocarcinoma of the stomach

Additional relevant MeSH terms:
Adenocarcinoma
Esophageal Neoplasms
Stomach Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Stomach Diseases
Fluorouracil
Oxaliplatin
Irinotecan
Docetaxel
Camptothecin
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on July 26, 2014