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Gastric CancerPhase 3NCT00941655

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

A Phase 3 study testing Oxaliplatin, Irinotecan and 5-Fluorouracil in people with Gastric Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Gastric Cancer
What is being tested?
Oxaliplatin, Irinotecan and 5-Fluorouracil
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
22 Jul 2009to 18 Jun 2012
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

None listed.

Who cannot join

  • 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.
Show all 13Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

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.
Read more

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.
Read the 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.
Conditions
Gastric Cancer
Being tested
Oxaliplatin, Irinotecan, 5-Fluorouracil, Leucovorin, Gastrectomy and/or metastasectomy
Keywords
Gastric Carcinoma, Chemotherapy, Liver Tumors, Peritoneal Tumors, Metastatic Gastric Cancer, Stomach Cancer, Gastric Cancer
Medical subject headings
Stomach Neoplasms, Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OxaliplatinDrug

    Also called Eloxatin

    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,

  • IrinotecanDrug

    Also called Camptosar

    Irinotecan 165 mg/m^2 IV over 90 minutes

  • 5-FluorouracilDrug

    Also called Efudex, Adracil, Carac

    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.

  • LeucovorinDrug

    Also called Folinic acid

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

    systemic chemotherapy - 200 mg/m^2 intravenous over 120 minutes.

  • Gastrectomy and/or metastasectomyProcedure or surgery

    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.

Study groups in NCT00941655
Study groupRoleWhat they receive
Surgery + HIPEC + Systemic ChemotherapyExperimentalSurgery -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.
Receives: Drug: Oxaliplatin; Drug: Irinotecan; Drug: 5-Fluorouracil; Drug: Leucovorin; Procedure: Gastrectomy and/or metastasectomy
Systemic Chemotherapy AloneExperimentalIrinotecan 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.
Receives: Drug: Oxaliplatin; Drug: Irinotecan; Drug: 5-Fluorouracil; Drug: Leucovorin

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

    Measured: 12 weeks up to 3 years

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

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

    Measured: 12 weeks up to 3 years

Secondary outcomes (9)

  1. Number of Participants With Serious and Non-Serious Adverse Events

    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.

    Measured: Date treatment consent signed to date off study, approximately, 40.5 months

  2. 12 Months Disease Free Survival (DFS)

    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.

    Measured: 12 months

  3. Gillys Stage Before and After Surgery

    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.

    Measured: Day 1

  4. Completeness of Cytoreduction (CCR) Score

    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.

    Measured: Day 1

  5. Median Blood Loss During Surgery

    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).

    Measured: Day 1

  6. Median Hospital Stay After Initial Surgery

    Recuperation period following complex surgery for this disease.

    Measured: 1-10 weeks

  7. Median Duration of Cytoreduction Surgery and Heated Intraperitoneal Chemotherapy (HIPEC)

    Time it takes to perform this complex surgery and HIPEC to reduce tumor burden overall in this disease.

    Measured: up to 12 hours

  8. Quality of Life (QOL) Parameters Between the Two Study Groups

    QOL tools Functional Assessment of Cancer Therapy - Gastric cancer (FACT-Ga) specifically developed for the assessment of QOL in gastric cancer patients.

    Measured: up to 3 years

  9. Patterns of Disease Recurrence Between the Two Therapeutic Approaches and Their Clinical Implications

    Compare surgery + heated intraperitoneal chemotherapy + systemic chemotherapy; and systemic chemotherapy alone to determine how each group responds clinically.

    Measured: up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jul 2009 (estimated)
  2. Study start22 Jul 2009
  3. Primary completion14 Jul 2011
  4. Study completion18 Jun 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00941655
Sponsor's protocol ID
090189
Other IDs
09-C-0189
Status last verified
Nov 2019
First submitted
16 Jul 2009
Last updated
13 Nov 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 8433390

  • 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.

    PubMed 15454251

  • 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.

    PubMed 12773978

  • 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.

    PubMed 25042700

  • 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.

    PubMed 20881648

  • 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.

    PubMed 20030854

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Oxaliplatin, Irinotecan and 5-Fluorouracil in people with Gastric Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 0 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Jul 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival in Patients With Limited Metastatic Gastric Carcinoma: Arm I (time frame: 12 weeks up to 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00941655, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2019.

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Clinical Trial NCT00941655 | AzTrials