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

Phase 3
18 Years
Not Enrolling
Gastric Cancer

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Trial Information

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


- 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.


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.


- MGC with limited metastatic disease thought to be resectable to no evidence of disease.

- 18 years old or greater with an ECOG 0-2

- Laboratory and physical examination parameters within acceptable limits by standard of
practice guidelines prior to surgery


- 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

- 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.

Inclusion Criteria


1. Histologically or cytologically confirmed gastric adenocarcinoma.

2. Metastatic disease must be measurable by CT and/or MRI


There must be a history of positive peritoneal washings or carcinomatosis

3. All disease should be deemed resectable to negative margins (NED) based on imaging

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

- 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

- Patients who present with both hepatic and peritoneal metastases must have no
evidence of extensive para-aortic/retro-pancreatic lymph node metastases.

4. Greater than or equal to 18 years of age.

5. Must be able to understand and sign the Informed Consent Document.

6. Clinical performance status of ECOG less than or equal to 2.

7. Life expectancy of greater than three months.

8. Patients of both genders must be willing to practice birth control during and for
four months after receiving chemotherapy.

9. Hematology:

- Absolute neutrophil count greater than 1300/mm(3) without the support of

- Platelet count greater than 75,000/mm(3).

- Hemoglobin greater than 8.0 g/dl.

10. Chemistry:

- Serum ALT/AST less than or equal to 5 times the upper limit of normal. Except in
the presence of obstructive liver metastases where ALT/AST may be up to 10 times
the upper limit of normal.

- Serum creatinine less than or equal to 1.5 mg/dl unless the measured creatinine
clearance is greater than 60 mL/min/1.73 m(2).

- Total bilirubin less than or equal to 2 mg/dl, except in the presence of
obstructive metastases.

- PT within 2 seconds of the upper limit of normal (INR less than or equal to

11. No history of prior/other malignancies within the 2 years prior to enrollment with
the exception of basal cell carcinoma.


1. Prior treatment with FOLFOXIRI (treatment with any of the components as separate
regimens is allowable).

2. Inability to tolerate any of the chemotherapeutic agents.

3. Grade 2 or greater neuropathy.

4. Women of child-bearing potential who are pregnant or breastfeeding because of the
potentially dangerous effects of the chemotherapy on the fetus or infant.

5. 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.

6. Brain metastases or a history of brain metastases.

7. Childs B or C cirrhosis or with evidence of severe portal hypertension by history,
endoscopy, or radiologic studies.

8. Weight less than 40 kg.

9. Significant ascites, greater than 1000cc in the absence of peritoneal disease.

10. History of congestive heart failure and/or an 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 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%.

11. Significant COPD or other chronic pulmonary restrictive disease with PFT's indicating
an FEV1 less than 50% or a 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.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To compare two therapeutic approaches-gastrectomy and/or metastasectomy followed by systemic chemotherapy vs. systemic chemotherapy-alone in terms of overall survival in patients with limited metastatic gastric carcinoma.

Principal Investigator

Udo Rudloff, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:




Start Date:

July 2009

Completion Date:

January 2013

Related Keywords:

  • Gastric Cancer
  • Gastric Carcinoma
  • Chemotherapy
  • Liver Tumors
  • Peritoneal Tumors
  • Metastatic Gastric Cancer
  • Stomach Cancer
  • Gastric Cancer
  • Stomach Neoplasms



National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892