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

• ClinicalTrials.gov Identifier: NCT01498289
• Recruitment Status: Completed
• First Posted: December 23, 2011
• Results First Posted: August 29, 2019
• Last Update Posted: November 7, 2019
• Sponsor: Southwest Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Southwest Oncology Group

Tracking Information

• First Submitted Date: December 22, 2011
• First Posted Date: December 23, 2011
• Results First Submitted Date: July 15, 2019
• Results First Posted Date: August 29, 2019
• Last Update Posted Date: November 7, 2019
• Actual Study Start Date: February 2012
• Actual Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 26, 2019)

• Progression-free Survival (PFS) in High-ERCC1 Patients [ Time Frame: 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 [ Time Frame: 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.
• Overall Survival (OS) [ Time Frame: Up to 3 years after registration ]
  OS is the length of time between protocol registration and patient death

Original Primary Outcome Measures (submitted: December 22, 2011)

• Progression-free survival (PFS) between high-ERCC1 and low-ERCC1 patients treated with FOLFOX versus irinotecan hydrochloride plus docetaxel
• PFS between low-ERCC1 and high-ERCC1 patients treated with FOLFOX

Current Secondary Outcome Measures (submitted: August 26, 2019)

• Overall Response Rate (ORR) [ Time Frame: 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.
• PFS Variation by ERCC1 [ Time Frame: 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.
• Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: December 22, 2011)

• Overall survival
• Response rate
• Toxicity

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Adenocarcinoma of the Gastroesophageal Junction
• Esophageal Cancer
• Gastric Cancer

Intervention

• Drug: FOLFOX regimen
  Given IV. Fluorouracil, oxaliplatin, & leucovorin calcium.
• 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: 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: 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
• 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

Study Arms

• 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.
  Interventions:

  • Drug: FOLFOX regimen
  • Drug: fluorouracil
  • Drug: leucovorin calcium
  • Drug: oxaliplatin
• 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.
  Interventions:

  • Drug: docetaxel
  • Drug: irinotecan hydrochloride

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 22, 2015): 213
• Original Estimated Enrollment (submitted: December 22, 2011): 225
• Actual Study Completion Date: September 19, 2019
• Actual Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 120 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01498289
• Other Study ID Numbers: S1201; S1201 ( Other Identifier: SWOG ); U10CA032102 ( U.S. NIH Grant/Contract ); NCI-2012-00096 ( Other Identifier: CTRP )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Southwest Oncology Group
• Study Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Syma Iqbal, MD; University of Southern California

• PRS Account: Southwest Oncology Group
• Verification Date: October 2019