Prospective Randomized Trial Comparing Gastrectomy, Metastasectomy Plus Systemic Therapy Versus Systemic Therapy Alone: GYMSSA Trial
Overview
- Phase
- Phase 3
- Intervention
- Irinotecan
- Conditions
- Gastric Cancer
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Overall Survival in Patients With Limited Metastatic Gastric Carcinoma: Arm I
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
Background:
- Gastric (stomach) cancer is a rare cancer. In most cases, by the time it has been diagnosed it has spread to other organs in the body and the chance of a cure is very small. The standard treatment for gastric cancer is a combination of chemotherapy drugs.
- Researchers are interested in finding out if surgically removing all tumors before beginning chemotherapy for stomach cancer can slow or halt its spread better than giving chemotherapy alone.
Objectives:
- To determine whether tumor removal surgery followed by chemotherapy is more effective in treating gastric cancer than chemotherapy given alone.
Eligibility:
- Patients 18 years of age and older who have been diagnosed with gastric cancer.
Design:
-
All patients will undergo an initial physical examination, blood tests, imaging scans, and a laparoscopy to determine the extent of the disease.
-
Half of the participants will be assigned to have surgery first and then chemotherapy; the other half will be assigned to have chemotherapy alone.
- The surgery-plus-chemotherapy group will have major surgery to remove all tumors in the stomach and abdominal area, followed by a recovery time of up to 4 weeks. Chemotherapy will begin 6 to 8 weeks after surgery.
- The chemotherapy-only group will begin treatment within 2 weeks of laparoscopy.
-
All patients will receive four chemotherapy drugs: 5-Fluorouracil, leucovorin, oxaliplatin, and irinotecan. The drugs are given intravenously over 2 days every 2 weeks (one cycle) for 12 cycles (about 6 months), either at the National Institutes of Health (NIH) Clinical Center or at home with a referring oncologist. Patients in the surgery group who have tumors in the peritoneum will receive an additional set of chemotherapy drugs in a separate treatment.
-
During the chemotherapy cycles, patients will provide blood samples approximately once a week and will have physical examinations and scans on a regular basis.
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Patients will return to the NIH Clinical Center for follow-up visits about every 4 months for 2 years, then every 6 months for 3 years and yearly thereafter.
Detailed Description
Background: * The standard of care for metastatic gastric cancer (MGC) is systemic therapy resulting in median survival of 6-12 months and rare survivors of up to three years. * For patients with limited MGC, retrospective studies have shown improved overall survival following gastrectomy and/or metastasectomy plus systemic therapy (e.g. median survival after liver resection for metastatic gastric cancer of 15-37 months, with a five year survival rate of 25%). * This prospective randomized trial for patients with MGC and limited metastases is designed to compare two therapeutic approaches-gastrectomy with metastasectomy plus systemic therapy (GYMS) vs. systemic therapy alone (SA)-- and to evaluate outcome in light of selection criteria to define those patients who may benefit from the more aggressive approach. Objectives: Primary Objective: - To compare two therapeutic approaches--GYMS vs. SA--in terms of overall survival in patients with limited MGC. Secondary Objectives: * To analyze selection criteria for patients who might benefit from the GYMS approach. * To determine progression-free survival in both arms. Eligibility: * MGC with limited metastatic disease thought to be resectable to no evidence of disease. * 18 years old or greater with an Eastern Cooperative Oncology Group (ECOG) 0-2 * Laboratory and physical examination parameters within acceptable limits by standard of practice guidelines prior to surgery Design: * Patients will be randomized to receive gastrectomy and metastasectomy followed by systemic chemotherapy (GYMS) or systemic chemotherapy (SA) alone and will be stratified based on sites of metastatic disease, previous therapy and disease free interval. * Patients in both arms will receive the FOLFOXIRI regimen (5-FU, leucovorin, oxaliplatin and irinotecan) * No cross over will be allowed. * Survival analysis will be done in intention to treat fashion from time of randomization. * Based on estimated 12 and 20 months overall survival for the SA and the GYMS arms respectively, 68 patients per arm (power=0.80, 0.05 two-tailed log-rank test) will be enrolled. Patients will be recruited over 6 years and followed for an additional 2 years from the date of entry of the last patient.
Investigators
Udo Rudloff, M.D.
Principal investigator
National Cancer Institute (NCI)
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Surgery + HIPEC + Systemic Chemotherapy
Surgery -gastric resection, metastasectomy, and heated intraperitoneal chemotherapy with Fluouracil (5-FU) 400 mg/m\^2 intravenous (IV) over 5 minutes. Leucovorin 20 mg/m\^2 IV and Oxaliplatin 460 mg/m\^2 diluted in 2.0 L/m\^2 of dextrose 5% in water (D5W) given as a heated intraperitoneal perfusion. Systemic chemotherapy - Irinotecan 165 mg/m\^2 IV over 90 minutes, Oxaliplatin 85 mg/m\^2 over 120 minutes, Leucovorin 200 mg/m\^2 IV 120 minutes, 5FU 3200 mg/m\^2 continuous IV infusion over 48 hours.
Intervention: Irinotecan
Surgery + HIPEC + Systemic Chemotherapy
Surgery -gastric resection, metastasectomy, and heated intraperitoneal chemotherapy with Fluouracil (5-FU) 400 mg/m\^2 intravenous (IV) over 5 minutes. Leucovorin 20 mg/m\^2 IV and Oxaliplatin 460 mg/m\^2 diluted in 2.0 L/m\^2 of dextrose 5% in water (D5W) given as a heated intraperitoneal perfusion. Systemic chemotherapy - Irinotecan 165 mg/m\^2 IV over 90 minutes, Oxaliplatin 85 mg/m\^2 over 120 minutes, Leucovorin 200 mg/m\^2 IV 120 minutes, 5FU 3200 mg/m\^2 continuous IV infusion over 48 hours.
Intervention: Oxaliplatin
Surgery + HIPEC + Systemic Chemotherapy
Surgery -gastric resection, metastasectomy, and heated intraperitoneal chemotherapy with Fluouracil (5-FU) 400 mg/m\^2 intravenous (IV) over 5 minutes. Leucovorin 20 mg/m\^2 IV and Oxaliplatin 460 mg/m\^2 diluted in 2.0 L/m\^2 of dextrose 5% in water (D5W) given as a heated intraperitoneal perfusion. Systemic chemotherapy - Irinotecan 165 mg/m\^2 IV over 90 minutes, Oxaliplatin 85 mg/m\^2 over 120 minutes, Leucovorin 200 mg/m\^2 IV 120 minutes, 5FU 3200 mg/m\^2 continuous IV infusion over 48 hours.
Intervention: 5-Fluorouracil
Surgery + HIPEC + Systemic Chemotherapy
Surgery -gastric resection, metastasectomy, and heated intraperitoneal chemotherapy with Fluouracil (5-FU) 400 mg/m\^2 intravenous (IV) over 5 minutes. Leucovorin 20 mg/m\^2 IV and Oxaliplatin 460 mg/m\^2 diluted in 2.0 L/m\^2 of dextrose 5% in water (D5W) given as a heated intraperitoneal perfusion. Systemic chemotherapy - Irinotecan 165 mg/m\^2 IV over 90 minutes, Oxaliplatin 85 mg/m\^2 over 120 minutes, Leucovorin 200 mg/m\^2 IV 120 minutes, 5FU 3200 mg/m\^2 continuous IV infusion over 48 hours.
Intervention: Leucovorin
Surgery + HIPEC + Systemic Chemotherapy
Surgery -gastric resection, metastasectomy, and heated intraperitoneal chemotherapy with Fluouracil (5-FU) 400 mg/m\^2 intravenous (IV) over 5 minutes. Leucovorin 20 mg/m\^2 IV and Oxaliplatin 460 mg/m\^2 diluted in 2.0 L/m\^2 of dextrose 5% in water (D5W) given as a heated intraperitoneal perfusion. Systemic chemotherapy - Irinotecan 165 mg/m\^2 IV over 90 minutes, Oxaliplatin 85 mg/m\^2 over 120 minutes, Leucovorin 200 mg/m\^2 IV 120 minutes, 5FU 3200 mg/m\^2 continuous IV infusion over 48 hours.
Intervention: Gastrectomy and/or metastasectomy
Systemic Chemotherapy Alone
Irinotecan 165 mg/m\^2 IV over 90 minutes, Oxaliplatin 85 mg/m\^2 over 120 minutes, Leucovorin 200 mg/m\^2 IV 120 minutes, 5FU 3200 mg/m\^2 continuous IV infusion over 48 hours.
Intervention: Oxaliplatin
Systemic Chemotherapy Alone
Irinotecan 165 mg/m\^2 IV over 90 minutes, Oxaliplatin 85 mg/m\^2 over 120 minutes, Leucovorin 200 mg/m\^2 IV 120 minutes, 5FU 3200 mg/m\^2 continuous IV infusion over 48 hours.
Intervention: Irinotecan
Systemic Chemotherapy Alone
Irinotecan 165 mg/m\^2 IV over 90 minutes, Oxaliplatin 85 mg/m\^2 over 120 minutes, Leucovorin 200 mg/m\^2 IV 120 minutes, 5FU 3200 mg/m\^2 continuous IV infusion over 48 hours.
Intervention: 5-Fluorouracil
Systemic Chemotherapy Alone
Irinotecan 165 mg/m\^2 IV over 90 minutes, Oxaliplatin 85 mg/m\^2 over 120 minutes, Leucovorin 200 mg/m\^2 IV 120 minutes, 5FU 3200 mg/m\^2 continuous IV infusion over 48 hours.
Intervention: Leucovorin
Outcomes
Primary Outcomes
Overall Survival in Patients With Limited Metastatic Gastric Carcinoma: Arm I
Time Frame: 12 weeks up to 3 years
Time between the first day of treatment and the date of death.
Overall Survival in Patients With Limited Metastatic Gastric Carcinoma: Arm II
Time Frame: 12 weeks up to 3 years
Time between the first day of treatment and the date of death
Secondary Outcomes
- Number of Participants With Serious and Non-Serious Adverse Events(Date treatment consent signed to date off study, approximately, 40.5 months)
- 12 Months Disease Free Survival (DFS)(12 months)
- Quality of Life (QOL) Parameters Between the Two Study Groups(up to 3 years)
- Patterns of Disease Recurrence Between the Two Therapeutic Approaches and Their Clinical Implications(up to 3 years)
- Median Hospital Stay After Initial Surgery(1-10 weeks)
- Gillys Stage Before and After Surgery(Day 1)
- Median Duration of Cytoreduction Surgery and Heated Intraperitoneal Chemotherapy (HIPEC)(up to 12 hours)
- Completeness of Cytoreduction (CCR) Score(Day 1)
- Median Blood Loss During Surgery(Day 1)