NCI HIGH PRIORITY CLINICAL TRIAL --- Phase III Randomized Study of Adjuvant Chemoradiotherapy with 5-FU/CF in Patients with Resected Gastric Cancer

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Alternate Title

Chemotherapy and Radiation Therapy or No Further Therapy Following Surgery in Treating Patients With Stomach Cancer

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIITreatmentClosedany ageNCISWOG-9008
CLB-9195, EST-6290, NCCTG-904151, RTOG-9018, INT-0116


I.  Compare disease-free and overall survival in patients randomized to 
adjuvant chemotherapy with fluorouracil/leucovorin administered with 
radiotherapy vs. no adjuvant therapy in patients with resected gastric cancer.

II.  Compare the incidence and patterns of disease failure on these two arms.

III.  Assess patient tolerance to upper abdominal chemoradiation after gastric 

Entry Criteria

Disease Characteristics:

Stage IB, II, IIIA/B, and IV (T4N2M0) adenocarcinoma of the stomach or
esophagogastric junction
  T2N0M0 eligible only if disease extends beyond the muscularis propria

  No M1 disease, including ascites, peritoneal seeding, liver metastasis, or
  extra-abdominal metastasis

  No recurrent cancer

Disease suitable for surgery with curative intent but at risk for later
failure (i.e., extension of disease beyond the muscularis propria and/or nodal
  En bloc resection of all known tumor required

  Radical subtotal or total gastrectomy with omentobursectomy and lymph node
  dissection recommended

  Surgical specimen must be adequate for TNM staging

  Microscopically positive resection margins exclude

Registration must occur between days 20 and 48 (or the next working day)
postsurgery; treatment must begin within 7 working days of registration or the
next Monday following day 41 postgastrectomy
  Evaluation by a radiation oncologist required prior to registration

Prior/Concurrent Therapy:

Biologic therapy:
  No prior immunotherapy allowed

  No prior chemotherapy allowed

Endocrine therapy:
  Not specified

  No prior radiotherapy allowed

  En bloc resection of all known tumor required

Patient Characteristics:

  Any age

Performance status:
  SWOG 0-2

  WBC at least 4,000
  Platelets above the institutional lower limit

  Bilirubin less than 1.5 x ULN
  SGOT less than 5 x ULN
  Alkaline phosphatase less than 5 x ULN

  Creatinine less than 1.25 x ULN
  Pre- or postoperative urogram, CT with contrast, or scan required
     If only 1 functioning kidney present, at least 2/3 of that kidney must be
     excluded from radiotherapy

  Estimated caloric intake (with oral nutritional supplementation, if
     required) must be at least 1,500 Kcal/day
  No second malignancy within the past 5 years except:
     Nonmelanomatous skin cancer
     Fully resected, noninvasive in situ cancer
  No active infection
  No pregnant or nursing women
  Effective contraception required of all fertile patients

Blood/body fluid analyses to determine eligibility completed within 14 days
prior to registration; screening exams other than blood/body fluid analyses
completed within 42 days prior to registration; imaging studies to determine
disease-free status completed within 56 days prior to registration

Expected Enrollment

550 patients will be randomized over an anticipated 66 months.  Interim 
analyses after each increment of 100 deaths will allow early closure if 
extreme results occur in either arm.


Randomized study.

Arm I:  Observation.  No adjuvant therapy.

Arm II:  Single-Agent Chemotherapy with Drug Modulation plus Radiotherapy.  
Fluorouracil, 5-FU, NSC-19893; with Leucovorin calcium, CF, NSC-3590; plus 
tumor bed irradiation using photons with energies of at least 6 MV (preferably 
10 MV or more).

Published Results

Gordon MA, Gundacker H, Benedetti J, et al.: Assessment of HER2 gene amplification in adenocarcinomas of the stomach or gastroesophageal junction in the INT-0116/SWOG9008 clinical trial. [Abstract] J Clin Oncol 30 (Suppl 15): A-4010, 2012.

Smalley SR, Benedetti JK, Haller DG, et al.: Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol 30 (19): 2327-33, 2012.[PUBMED Abstract]

Macdonald JS, Benedetti J, Smalley S, et al.: Chemoradiation of resected gastric cancer: A 10-year follow-up of the phase III trial INT0116 (SWOG 9008). [Abstract] J Clin Oncol 27 (Suppl 15): A-4515, 2009.

Wang J, Liang M, Hackett C, et al.: Correlation between p16 expression, loss of heterozygosity and survival in advanced gastric cancer. [Abstract] United States and Canadian Academy of Pathology 96th Annual Meeting, March 24-30, 2007, San Diego, CA. A-593, 2007.

Wang J, Liang M, Liu B, et al.: Loss of heterozygosity of p16 gene may predict response to chemoradiation therapy in advanced gastric cancer. [Abstract] United States and Canadian Academy of Pathology 95th Annual Meeting, February 11-17, 2006, Atlanta, GA. A-560, 2006.

Macdonald JS, Smalley S, Benedetti J: Postoperative combined radiation and chemotherapy improves disease-free survival (DFS) and overall survival (OS) in resected adenocarcinoma of the stomach and gastroesophageal junction: update of the results of Intergroup Study INT-0116 (SWOG 9008). [Abstract] American Society of Clinical Oncology 2004 Gastrointestinal Cancers Symposium, 22-24 January 2004, San Francisco, CA. A-6, 2004.

Clements WM, Wang J, Sarnaik A, et al.: beta-Catenin mutation is a frequent cause of Wnt pathway activation in gastric cancer. Cancer Res 62 (12): 3503-6, 2002.[PUBMED Abstract]

Hundahl SA, Macdonald JS, Benedetti J, et al.: Surgical treatment variation in a prospective, randomized trial of chemoradiotherapy in gastric cancer: the effect of undertreatment. Ann Surg Oncol 9 (3): 278-86, 2002.[PUBMED Abstract]

Macdonald JS, Smalley SR, Benedetti J, et al.: Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 345 (10): 725-30, 2001.[PUBMED Abstract]

Macdonald JS, Smalley S, Benedetti J, et al.: Postoperative combined radiation and chemotherapy improves disease-free survival (DFS) and overall survival (OS) in resected adenocarcinoma of the stomach and G.E. junction. Results of Intergroup Study INT-0116 (SWOG 9008). [Abstract] Proceedings of the American Society of Clinical Oncology 19: A1, 2000.

Shepherd T, Tolbert D, Benedetti J, et al.: Alterations in exon 4 of the p53 gene in gastric carcinoma. Gastroenterology 118 (6): 1039-44, 2000.[PUBMED Abstract]

Related Publications

Kundel Y, Purim O, Idelevich E, et al.: Postoperative chemoradiation for resected gastric cancer--is the Macdonald Regimen Tolerable? a retrospective multi-institutional study. Radiat Oncol 6: 127, 2011.[PUBMED Abstract]

Coburn NG, Guller U, Baxter NN, et al.: Adjuvant therapy for resected gastric cancer--rapid, yet incomplete adoption following results of intergroup 0116 trial. Int J Radiat Oncol Biol Phys 70 (4): 1073-80, 2008.[PUBMED Abstract]

Wang SJ, Fuller CD, Scarbrough TJ, et al.: A cost-effectiveness analysis of SWOG 9008: adjuvant chemoradiation therapy for gastric cancer. [Abstract] American Society of Clinical Oncology 2007 Gastrointestinal Cancers Symposium, 19 -21 January 2007, Orlando, Florida A-36, 2007.

Kerwin TL, Miller MJ, Tome MA: Adjuvant chemoradiotherapy for gastric adenocarcinoma: Kaiser institutional experience with INT 0116. [Abstract] J Clin Oncol 24 (Suppl 18): A-14114, 2006.

Macdonald JS: Role of post-operative chemoradiation in resected gastric cancer. J Surg Oncol 90 (3): 166-70, 2005.[PUBMED Abstract]

Macdonald JS: Treatment of localized gastric cancer. Semin Oncol 31 (4): 566-73, 2004.[PUBMED Abstract]

Smalley SR, Gunderson L, Tepper J, et al.: Gastric surgical adjuvant radiotherapy consensus report: rationale and treatment implementation. Int J Radiat Oncol Biol Phys 52 (2): 283-93, 2002.[PUBMED Abstract]

Kim OJ, Stemmermann G, DeVoe G, et al.: E-cadherin, a and b-catenins in gastric cancer expression. [Abstract] Mod Pathol 14: A-506, 88A, 2001.

Estes NC, MacDonald JS, Touijer K, et al.: Inadequate documentation and resection for gastric cancer in the United States: a preliminary report. Am Surg 64 (7): 680-5, 1998.[PUBMED Abstract]

Fenoglio-Preiser CM, Noffsinger AE, Belli J, et al.: Pathologic and phenotypic features of gastric cancer. Semin Oncol 23 (3): 292-306, 1996.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

John MacDonald, MD, Protocol chair
Ph: 212-604-6011; 888-442-2623

Radiation Therapy Oncology Group

Leonard Gunderson, MD, Protocol chair
Ph: 480-301-7351

North Central Cancer Treatment Group

James Martenson, MD, Protocol chair
Ph: 507-284-4561

Eastern Cooperative Oncology Group

Daniel Haller, MD, Protocol chair
Ph: 215-662-6318

Cancer and Leukemia Group B

John Jessup, MD, Protocol chair (Contact information may not be current)
Ph: 412-692-2990

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.