Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	UCCRC-10325 CWRU-1699, NCI-T99-0111, NCT00005961, T99-0111

Objectives

1. 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.
2. Compare the toxicities of this regimen in patients with no prior chemotherapy vs prior chemotherapy failure.
3. 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.

Entry Criteria

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

Prior/Concurrent Therapy:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics
• 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

Endocrine therapy:

• Not specified

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

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

• WBC at least 3,000/mm³
• Absolute neutrophil count at least 1,200/mm³
• Platelet count at least 100,000/mm³

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

Expected Enrollment

A total of 24-41 patients will be accrued for the chemotherapy failure stratum and a total of 18-35 patients will be accrued for the chemotherapy naive stratum of this study.

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.

Trial Contact Information

Trial Lead Organizations

University of Chicago Cancer Research Center

Thomas Gajewski, MD, PhD, Protocol chair		Ph: 773-702-4601; 888-824-0200 Email: tgajewsk@medicine.bsd.uchicago.edu

Registry Information
Official Title		A Phase II Trial of O6-Benzylguanine (NSC 637037) and BCNU (Carmustine) in Patients with Metatstatic Melanoma
Trial Start Date		2000-06-09
Registered in ClinicalTrials.gov		NCT00005961
Date Submitted to PDQ		2000-05-04
Information Last Verified		2003-04-10
NCI Grant/Contract Number		CA14599, CA63187