NCI HIGH PRIORITY CLINICAL TRIAL --- Phase III Study of Adjuvant Postoperative Interferon alpha in Melanoma Patients at High Risk for Recurrence: High Dose for 1 Year vs Chronic Low Dose vs No Treatment
Basic Trial Information
|Phase III||Treatment||Closed||physiologic 18-70||NCI||EST-1690|
CLB-9190, SWOG-9111, E1690
I. Establish the efficacy of 1 year of adjuvant treatment with interferon alpha (IFN-A) at maximum tolerated doses in improving the disease-free and overall survival of melanoma patients at high risk for recurrence after definitive surgery for deep primary lesions or for regional lymph node recurrence. II. Evaluate the efficacy and tolerance of long-term adjuvant low-dose (3 MU/day, 3 x weekly) IFN-A in comparison to 1 year of treatment at maximum tolerated doses in the same patient population.
Completely resected, histopathologically documented cutaneous melanoma of 1 of the following TNM stages at high risk for recurrence: T4 N0 M0 (deep primary, i.e., greater than 4 mm Breslow depth, with or without lymphadenectomy) T1-4 N1 M0 (primary melanoma with regional lymph node metastases found at lymphadenectomy but clinically undetectable, i.e., occult) T1-4 N1-2 M0 (primary melanoma with clinically apparent, i.e., overt, regional lymph node metastases confirmed by lymphadenectomy) T1-4 N1-2 M0 (recurrence of melanoma at the site of proximal regional lymph node resection) Definitive surgery and randomization within 56 days of initial biopsy required, as follows: Wide excision of primary with 2 cm margins Full lymphadenectomy Lymphadenectomy not required in T4 N0 M0 patients Pathologic confirmation of adequate surgical margins (e.g., 2 cm minimum for lesions of greater than 1 mm Breslow depth) required Distal interphalangeal amputation required for subungual melanoma Randomization within 42 days of lymphadenectomy required in patients entering with recurrent regional lymph node disease No melanoma of unknown or noncutaneous primary site No local recurrence or satellite lesions No more than 1 involved lymph node group allowed No extra nodal extension or soft tissue invasion Registration on protocol E-2690 (An Evaluation of the In Vivo Mechanism of Interferon Alfa-2b) prior to registration on this protocol required unless ineligible solely because of HIV or hepatitis B infection
Biologic therapy: No prior adjuvant immunotherapy Chemotherapy: No prior adjuvant chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior adjuvant radiotherapy Surgery: Complete surgical resection required Other: No preoperative infusion or perfusion therapy No concurrent requirement for the following: Steroids Nonsteroidal anti-inflammatory agents Other prostaglandin synthetase inhibitors Antihistamines Other immunomodulators
Age: Physiologic 18 to 70 Performance status: ECOG 0 or 1 Hematopoietic: WBC at least 4,000 Platelets at least 125,000 Hematocrit at least 33% Hepatic: Bilirubin no more than 2 x normal SGOT no more than 2 x normal Renal: Creatinine no greater than 1.8 mg/dl BUN no greater than 33 mg/dl Cardiovascular: No CHF (NYHA classification greater than 2) No history of treatment with anthracyclines No ventricular or supraventricular arrhythmia requiring treatment Other: No medical or psychiatric disorders precluding therapy, e.g.: No organic brain syndrome No significant impairment of basal cognitive function No depression No second malignancy except: In situ cervical cancer Basal and squamous cell skin cancer (exceptions may be discussed with study chairman)
A total of 625 patients will be entered over an estimated 4.5 years.
Randomized study. Arm I: Biological Response Modifier Therapy. Interferon alpha (Schering), IFN-A, NSC-377523. High dose for 1 year. Arm II: Biological Response Modifier Therapy. IFN-A. Chronic low dose. Arm III: No Further Treatment.
Chen M, Harrington DP, Ibrahim JG: Bayesian cure rate models for malignant melanoma: a case-study of Eastern Cooperative Oncology Group trial E1690 . [Abstract] J R Stat Soc Ser C Appl Stat 51 (2): 135-50, 2002.
Kirkwood JM, Richards T, Zarour HM, et al.: Immunomodulatory effects of high-dose and low-dose interferon alpha2b in patients with high-risk resected melanoma: the E2690 laboratory corollary of intergroup adjuvant trial E1690. Cancer 95 (5): 1101-12, 2002.[PUBMED Abstract]
Rao UN, Ibrahim J, Flaherty LE, et al.: Implications of microscopic satellites of the primary and extracapsular lymph node spread in patients with high-risk melanoma: pathologic corollary of Eastern Cooperative Oncology Group Trial E1690. J Clin Oncol 20 (8): 2053-7, 2002.[PUBMED Abstract]
Kirkwood JM, Ibrahim JG, Sondak VK, et al.: High- and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. J Clin Oncol 18 (12): 2444-58, 2000.[PUBMED Abstract]
Kirkwood JM, Ibrahim J, Sondak V, et al.: Preliminary analysis of the E1690/S9111/C9190 Intergroup postoperative adjuvant trial of high-and-low-dose IFNa2b (HDI and LDI) in high-risk primary or lymph node metastatic melanoma. [Abstract] Proceedings of the American Society of Clinical Oncology 18: A2072, 537a, 1999.
Ibrahim JG, Chen MH, Chu H: Bayesian methods in clinical trials: a Bayesian analysis of ECOG trials E1684 and E1690. BMC Med Res Methodol 12: 183, 2012.[PUBMED Abstract]
Rao UN, Lee SJ, Luo W, et al.: Presence of tumor-infiltrating lymphocytes and a dominant nodule within primary melanoma are prognostic factors for relapse-free survival of patients with thick (t4) primary melanoma: pathologic analysis of the e1690 and e1694 intergroup trials. Am J Clin Pathol 133 (4): 646-53, 2010.[PUBMED Abstract]
Bonetti M, Gigliarano C, Muliere P: The Gini concentration test for survival data. Lifetime Data Anal 15 (4): 493-518, 2009.[PUBMED Abstract]
Kilbridge KL, Cole BF, Kirkwood JM, et al.: Quality-of-life-adjusted survival analysis of high-dose adjuvant interferon alpha-2b for high-risk melanoma patients using intergroup clinical trial data. J Clin Oncol 20 (5): 1311-8, 2002.[PUBMED Abstract]
Kilbridge KL, Cole B, Weeks JC, et al.: Quality-of-life (QOL) adjusted analysis of high-dose adjuvant interferon alfa-2B (HDI) for melanoma based on E1694/S9512/C509801, E1690/S9111/C9190 and E1684. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1398, 2002.
Kirkwood JM, Manola J, Ibraham J, et al.: Pooled-analysis of four ECOG/Intergroup trials of high-dose interferon Alfa-2b (HDI) in 1916 patients with high-risk resected cutaneous melanoma. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-1395, 2001.
Sondak VK, Wolfe JA: Adjuvant therapy for melanoma. Curr Opin Oncol 9 (2): 189-204, 1997.[PUBMED Abstract]
Trial Contact Information
Trial Lead Organizations
Eastern Cooperative Oncology Group
Southwest Oncology Group
Ph: 313-576-8715; 800-527-6266
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.