Prospective Randomized Trial Comparing Gastrectomy, Metastasectomy Plus Systemic Therapy Versus Systemic Therapy Alone: GYMSSA Trial
- Conditions
- Gastric Cancer
- Interventions
- Procedure: Gastrectomy and/or metastasectomy
- Registration Number
- NCT00941655
- Lead Sponsor
- National Cancer Institute (NCI)
- 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.
* 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 15
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Surgery + HIPEC + Systemic Chemotherapy Gastrectomy and/or metastasectomy 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. Surgery + HIPEC + Systemic Chemotherapy Oxaliplatin 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. Surgery + HIPEC + Systemic Chemotherapy Irinotecan 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. Surgery + HIPEC + Systemic Chemotherapy 5-Fluorouracil 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. Surgery + HIPEC + Systemic Chemotherapy Leucovorin 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. Systemic Chemotherapy Alone Oxaliplatin 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. Systemic Chemotherapy Alone Irinotecan 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. Systemic Chemotherapy Alone 5-Fluorouracil 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. Systemic Chemotherapy Alone Leucovorin 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.
- Primary Outcome Measures
Name Time Method Overall Survival in Patients With Limited Metastatic Gastric Carcinoma: Arm II 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 I 12 weeks up to 3 years Time between the first day of treatment and the date of death.
- Secondary Outcome Measures
Name Time Method Number of Participants With Serious and Non-Serious Adverse Events Date treatment consent signed to date off study, approximately, 40.5 months Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
12 Months Disease Free Survival (DFS) 12 months Participants who were alive and disease free at 12 months. DFS was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response was disappearance of all target lesions. Partial response was at least a 30% decrease in target lesions. Progression was at least a 20% increase in target lesions and stable disease is neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.
Quality of Life (QOL) Parameters Between the Two Study Groups up to 3 years QOL tools Functional Assessment of Cancer Therapy - Gastric cancer (FACT-Ga) specifically developed for the assessment of QOL in gastric cancer patients.
Patterns of Disease Recurrence Between the Two Therapeutic Approaches and Their Clinical Implications up to 3 years Compare surgery + heated intraperitoneal chemotherapy + systemic chemotherapy; and systemic chemotherapy alone to determine how each group responds clinically.
Gillys Stage Before and After Surgery Day 1 Gillys stage measures the completeness of the cytoreduction and is recorded before and after surgery. It is used to classify disease burden and determine prognosis. Stage 0 is no macroscopic signs of disease, stage 1 is nodules \>5mm in one part of the abdomen, stage 2 is nodules \>5 mm throughout the abdomen, stage 3 is nodules 5mm to 2 cm, and stage 4 is nodules \< 2 cm.
Median Hospital Stay After Initial Surgery 1-10 weeks Recuperation period following complex surgery for this disease.
Median Duration of Cytoreduction Surgery and Heated Intraperitoneal Chemotherapy (HIPEC) up to 12 hours Time it takes to perform this complex surgery and HIPEC to reduce tumor burden overall in this disease.
Completeness of Cytoreduction (CCR) Score Day 1 CCR is assessed by Sugarbaker's criteria. CCR-0 is no residual tumor. CCR-1 is no residual nodules greater than 2.5 mm in diameter, CCR-2 is no residual nodules greater than 25 mm, and CCR-3 is residual nodules greater than 25 mm.
Median Blood Loss During Surgery Day 1 Blood loss during surgery is related to complexity of the operation and via that to the stage of disease (more tumor to be cytoreduced, more blood loss).
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
🇺🇸Bethesda, Maryland, United States