O6-benzylguanine and Carmustine in Treating Patients With Unresectable Locally Recurrent or Metastatic Melanoma

A Phase II Trial of O6-Benzylguanine (NSC 637037) and BCNU (Carmustine) in Patients With Metatstatic Melanoma

Phase II trial to study the effectiveness of O6-benzylguanine and carmustine in treating patients who have unresectable locally recurrent or metastatic melanoma. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than once chemotherapy drug may kill more tumor cells.

Study Overview

• Status: Completed
• Conditions: Melanoma (Skin)
• Intervention / Treatment: Drug: O6-benzylguanine; Drug: carmustine

Detailed Description

OBJECTIVES:

I. Determine the objective clinical response rate and duration of response in patients with unresectable locally recurrent or metastatic melanoma treated with O6-benzylguanine and carmustine.

II. Compare the toxicities of this regimen in patients with no prior chemotherapy vs prior chemotherapy failure.

III. Correlate clinical response to this regimen in these patients with O6-alkylguanine DNA alkyltransferase (AGT) depletion and baseline AGT in peripheral blood mononuclear cells and tumor tissue.

OUTLINE: This is a multicenter study. Patients are stratified according to prior chemotherapy (chemotherapy failure vs chemotherapy naive).

Patients receive O6-benzylguanine IV over 1 hour, followed 1 hour later by carmustine IV over 1 hour on day 1. Treatment continues every 6 weeks for a minimum of 2 courses in the absence of disease progression or unacceptable toxicity.

Patients with disease progression are followed every 6 months. All other patients are followed every 3 months for 1 year.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Cancer Research Center
    • Chicago, Illinois, United States, 60640
      • Louis A. Weiss Memorial Hospital
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago Health Sciences Center
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital Cancer Care Institute
    • Evanston, Illinois, United States, 60201
      • Evanston Northwestern Health Care
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Park Ridge, Illinois, United States, 60068
      • Lutheran General Cancer Care Center
    • Peoria, Illinois, United States, 61602
      • Oncology/Hematology Associates of Central Illinois, P.C.
    • Springfield, Illinois, United States, 62701
      • Central Illinois Hematology Oncology Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46885-5099
      • Fort Wayne Medical Oncology and Hematology, Incorporated
    • South Bend, Indiana, United States, 46617
      • Michiana Hematology/Oncology P.C.
  • Ohio
    • Canton, Ohio, United States, 44708
      • Mercy Ireland Cancer Center
    • Cleveland, Ohio, United States, 44106-5065
      • Ireland Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically proven unresectable locally recurrent or metastatic melanoma

  • Chemotherapy naive with no more than 2 prior immunotherapy regimens (including cytokines, vaccines, or adjuvant interferon) OR
  • Prior chemotherapy failure with no more than 2 prior immunotherapy regimens (including adjuvant interferon) and no more than 1 prior chemotherapy regimen (which may include carmustine) not including antiangiogenesis therapy

• Measurable disease

  • At least 20 mm in at least 1 dimension by conventional technique OR at least 10 mm in at least 1 dimension by spiral CT scan
• No disease confined only to the CNS
• No uncontrolled symptomatic brain metastases regardless of other disease sites

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• WBC at least 3,000/mm^3
• Absolute neutrophil count at least 1,200/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• AST and/or ALT no greater than 3 times upper limit of normal
• PT normal

Renal:

• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance greater than 60 mL/min

Pulmonary:

• DLCO at least 70% predicted

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No concurrent significant psychiatric or medical illness, including active infections, that would interfere with study therapy or increase risk
• No other malignancy within the past 5 years except curatively treated nonmelanomatous skin cancer, carcinoma in situ of the cervix, or superficial bladder cancer

PRIOR CONCURRENT THERAPY:

Chemotherapy:

• At least 4 weeks since prior systemic chemotherapy (at least 6 weeks since prior carmustine or mitomycin) and recovered
• No other concurrent chemotherapy or investigational antineoplastic drugs

Radiotherapy:

• At least 2 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy

Surgery:

• At least 3 weeks since prior major surgery and recovered

Other:

• At least 4 weeks since other prior anticancer systemic therapy and recovered

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Patients receive O6-benzylguanine IV over 1 hour, followed 1 hour later by carmustine IV over 1 hour on day 1. Treatment continues every 6 weeks for a minimum of 2 courses in the absence of disease progression or unacceptable toxicity.	Drug: O6-benzylguanine; Drug: carmustine

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Study Chair: Thomas F. Gajewski, MD, PhD, University of Chicago

Study record dates

Study Major Dates

• Study Start: June 1, 2000
• Primary Completion (Actual): December 1, 2005

Study Registration Dates

• First Submitted: July 5, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): February 11, 2013
• Last Update Submitted That Met QC Criteria: February 8, 2013
• Last Verified: April 1, 2003

More Information

Terms related to this study

• Keywords: recurrent melanoma; stage IV melanoma; stage III melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Carmustine; O(6)-benzylguanine
• Other Study ID Numbers: NCI-2012-02340; UCCRC-10325; CWRU-1699; NCI-T99-0111; CDR0000067943 (Registry Identifier: PDQ (Physician Data Query))