Prospective Randomized Trial Comparing Gastrectomy, Metastasectomy Plus Systemic Therapy Versus Systemic Therapy Alone: GYMSSA Trial

NCT00941655 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 09018909-C-0189
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Gastric Cancer

Keywords

Gastric Carcinoma; Chemotherapy; Liver Tumors; Peritoneal Tumors; Metastatic Gastric Cancer; Stomach Cancer; Gastric Cancer

Outcome Measures

Primary Outcomes (2)

• Overall Survival in Patients With Limited Metastatic Gastric Carcinoma: Arm I

  Time between the first day of treatment and the date of death.

  12 weeks up to 3 years

• Overall Survival in Patients With Limited Metastatic Gastric Carcinoma: Arm II

  Time between the first day of treatment and the date of death

  12 weeks up to 3 years

Secondary Outcomes (9)

• 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

• Gillys Stage Before and After Surgery

  Day 1

• Completeness of Cytoreduction (CCR) Score

  Day 1

• Median Blood Loss During Surgery

  Day 1

Study Arms (2)

Surgery + HIPEC + Systemic Chemotherapy

EXPERIMENTAL

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.

Drug: Oxaliplatin; Drug: Irinotecan; Drug: 5-Fluorouracil; Drug: Leucovorin; Procedure: Gastrectomy and/or metastasectomy

Systemic Chemotherapy Alone

EXPERIMENTAL

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.

Drug: Oxaliplatin; Drug: Irinotecan; Drug: 5-Fluorouracil; Drug: Leucovorin

Interventions

Oxaliplatin DRUG

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 - Oxaliplatin 85 mg/m\^2 over 120 minutes,

Also known as: Eloxatin

Surgery + HIPEC + Systemic Chemotherapy; Systemic Chemotherapy Alone

Irinotecan DRUG

Irinotecan 165 mg/m\^2 IV over 90 minutes

Also known as: Camptosar

Surgery + HIPEC + Systemic Chemotherapy; Systemic Chemotherapy Alone

5-Fluorouracil DRUG

Surgery and heated intraperitoneal chemotherapy with Fluouracil (5-FU) 400 mg/m\^2 intravenous (IV) over 5 minutes. systemic chemotherapy -3200 mg/m\^2 continuous intravenous over 48 hours.

Also known as: Efudex, Adracil, Carac

Surgery + HIPEC + Systemic Chemotherapy; Systemic Chemotherapy Alone

Leucovorin DRUG

surgery and heated intraperitoneal chemotherapy -20 mg/m\^2 intravenous over 5 minutes. systemic chemotherapy - 200 mg/m\^2 intravenous over 120 minutes.

Also known as: Folinic acid

Surgery + HIPEC + Systemic Chemotherapy; Systemic Chemotherapy Alone

Gastrectomy and/or metastasectomy PROCEDURE

Gastrectomy: tumor resection and a bypass; palliative treatment for pain, bleeding, obstruction and/or if deemed in the best interest of the patient. Metastasectomy: anatomical segmental resection to render the patient no evidence of disease (NED) with at least 1cm negative margins when possible, followed by systemic chemotherapy.

Surgery + HIPEC + Systemic Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed gastric adenocarcinoma.
• Metastatic disease must be measurable by computed tomography (CT) and/or magnetic resonance imaging (MRI)
• There must be a history of positive peritoneal washings or carcinomatosis
• All disease should be deemed resectable to negative margins (NED) based on imaging studies.
• Note: Patients with both pulmonary and peritoneal metastases will be enrolled at the discretion of the Principal Investigator.
• Esophageal invasion \< 4cm that does not require thoracotomy (Seiwert II and III lesions).
• Hepatic metastases (unilateral or bilateral less than or equal to 5 lesions, less than or equal to 15 cm total diameter).
• Primary peritoneal metastases (small disease load less than or equal to P2 disease) without massive ascites or intestinal obstruction.
• Para-aortic lymph node metastases (stations 16 a1 and/or b2).
• Lung metastases (less than or equal to 3 unilateral/bilateral, 9 cm total diameter).
• Patients who present with both hepatic and peritoneal metastases must have no evidence of extensive para-aortic/retro-pancreatic lymph node metastases.
• Greater than or equal to 18 years of age.
• Must be able to understand and sign the Informed Consent Document.
• Clinical performance status of Eastern Cooperative Oncology Group (ECOG) less than or equal to 2.
• Life expectancy of greater than three months.

You may not qualify if:

• Prior treatment with 5-FU, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) (treatment with any of the components as separate regimens is allowable).
• Inability to tolerate any of the chemotherapeutic agents.
• Grade 2 or greater neuropathy.
• Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the chemotherapy on the fetus or infant.
• Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system; myocardial infarction; cardiac arrhythmias; obstructive or restrictive pulmonary disease.
• Brain metastases or a history of brain metastases.
• Childs B or C cirrhosis or with evidence of severe portal hypertension by history, endoscopy, or radiologic studies.
• Weight less than 40 kg.
• Significant ascites, greater than 1000cc in the absence of peritoneal disease.
• History of congestive heart failure and/or an left ventricular ejection fraction (LVEF) less than 40%.
• Note: Patients at increased risk for coronary artery disease or cardiac dysfunction (e.g., greater than 65yo, diabetes, history of hypertension, elevated low-density lipoprotein (LDL), first degree relative with coronary artery disease) will undergo full cardiac evaluation and will not be eligible if they demonstrate significant irreversible ischemia on stress thallium or an ejection fraction \< 40%.
• Significant chronic obstructive pulmonary disease (COPD) or other chronic pulmonary restrictive disease with pulmonary function tests (PFT's) indicating an forced expiratory volume 1 (FEV1) less than 50% or a carbon monoxide diffusing capacity (DLCO) less than 40% predicted for age.
• Note: Patients who have shortness of breath with minimal exertion or who are at risk for pulmonary disease (e.g., chronic smokers) will undergo pulmonary function testing and will not be eligible if their FEV1 is less than 50% of expected.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (6)

• Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993 Mar 3;85(5):365-76. doi: 10.1093/jnci/85.5.365.

  PMID: 8433390 BACKGROUND

• Blazeby JM, Conroy T, Bottomley A, Vickery C, Arraras J, Sezer O, Moore J, Koller M, Turhal NS, Stuart R, Van Cutsem E, D'haese S, Coens C; European Organisation for Research and Treatment of Cancer Gastrointestinal and Quality of Life Groups. Clinical and psychometric validation of a questionnaire module, the EORTC QLQ-STO 22, to assess quality of life in patients with gastric cancer. Eur J Cancer. 2004 Oct;40(15):2260-8. doi: 10.1016/j.ejca.2004.05.023.

  PMID: 15454251 BACKGROUND

• Sakamoto Y, Ohyama S, Yamamoto J, Yamada K, Seki M, Ohta K, Kokudo N, Yamaguchi T, Muto T, Makuuchi M. Surgical resection of liver metastases of gastric cancer: an analysis of a 17-year experience with 22 patients. Surgery. 2003 May;133(5):507-11. doi: 10.1067/msy.2003.147.

  PMID: 12773978 BACKGROUND

• Rudloff U, Langan RC, Mullinax JE, Beane JD, Steinberg SM, Beresnev T, Webb CC, Walker M, Toomey MA, Schrump D, Pandalai P, Stojadinovic A, Avital I. Impact of maximal cytoreductive surgery plus regional heated intraperitoneal chemotherapy (HIPEC) on outcome of patients with peritoneal carcinomatosis of gastric origin: results of the GYMSSA trial. J Surg Oncol. 2014 Sep;110(3):275-84. doi: 10.1002/jso.23633. Epub 2014 Jul 5.

  PMID: 25042700 RESULT

• Kemp CD, Kitano M, Kerkar S, Ripley RT, Marquardt JU, Schrump DS, Avital I. Pulmonary resection for metastatic gastric cancer. J Thorac Oncol. 2010 Nov;5(11):1796-805. doi: 10.1097/JTO.0b013e3181ed3514.

  PMID: 20881648 DERIVED

• Kerkar SP, Kemp CD, Duffy A, Kammula US, Schrump DS, Kwong KF, Quezado M, Goldspiel BR, Venkatesan A, Berger A, Walker M, Toomey MA, Steinberg SM, Giaccone G, Rosenberg SA, Avital I. The GYMSSA trial: a prospective randomized trial comparing gastrectomy, metastasectomy plus systemic therapy versus systemic therapy alone. Trials. 2009 Dec 23;10:121. doi: 10.1186/1745-6215-10-121.

  PMID: 20030854 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms; Carcinoma, Hepatocellular

Interventions

Oxaliplatin; Irinotecan; Fluorouracil; Leucovorin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Liver Neoplasms; Liver Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Heterocyclic Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Results Point of Contact

• Title: Dr. Udo Rudloff
• Organization: National Cancer Institute, National Institutes of Health

Udo.Rudloff@nih.gov

301-496-3098

Study Officials

• Udo Rudloff, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: July 16, 2009
• First Posted: July 17, 2009
• Study Start: July 22, 2009
• Primary Completion: July 14, 2011
• Study Completion: June 18, 2012
• Last Updated: November 13, 2019
• Results First Posted: July 11, 2013

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)