NCI HIGH PRIORITY CLINICAL TRIAL --- Phase III Randomized Study of Adjuvant Chemoradiotherapy with 5-FU/CF in Patients with Resected Gastric Cancer
Chemotherapy and Radiation Therapy or No Further Therapy Following Surgery in Treating Patients With Stomach Cancer
Basic Trial Information
|Phase III||Treatment||Closed||any age||NCI||SWOG-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 resection.
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 involvement) 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
Biologic therapy: No prior immunotherapy allowed Chemotherapy: No prior chemotherapy allowed Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy allowed Surgery: En bloc resection of all known tumor required
Age: Any age Performance status: SWOG 0-2 Hematopoietic: WBC at least 4,000 Platelets above the institutional lower limit Hepatic: Bilirubin less than 1.5 x ULN SGOT less than 5 x ULN Alkaline phosphatase less than 5 x ULN Renal: 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 Other: 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
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).
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]
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.
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]
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
Ph: 212-604-6011; 888-442-2623
Radiation Therapy Oncology Group
North Central Cancer Treatment Group
Eastern Cooperative Oncology Group
Cancer and Leukemia Group B
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.