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

NCT ID: NCT00005961

Last Updated: 2013-02-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-06-30

Brief Summary

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.

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.

Conditions

Melanoma (Skin)

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

O6-benzylguanine

Intervention Type: DRUG

carmustine

Intervention Type: DRUG

Interventions

O6-benzylguanine

Intervention Type: DRUG

carmustine

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas F. Gajewski, MD, PhD

Role: STUDY_CHAIR

University of Chicago

Locations

University of Illinois at Chicago Health Sciences Center

Chicago, Illinois, United States

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Louis A. Weiss Memorial Hospital

Chicago, Illinois, United States

Decatur Memorial Hospital Cancer Care Institute

Decatur, Illinois, United States

Evanston Northwestern Health Care

Evanston, Illinois, United States

Loyola University Medical Center

Maywood, Illinois, United States

Lutheran General Cancer Care Center

Park Ridge, Illinois, United States

Oncology/Hematology Associates of Central Illinois, P.C.

Peoria, Illinois, United States

Central Illinois Hematology Oncology Center

Springfield, Illinois, United States

Fort Wayne Medical Oncology and Hematology, Incorporated

Fort Wayne, Indiana, United States

Michiana Hematology/Oncology P.C.

South Bend, Indiana, United States

Mercy Ireland Cancer Center

Canton, Ohio, United States

Ireland Cancer Center

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

UCCRC-10325

Identifier Type: -

Identifier Source: secondary_id

CWRU-1699

Identifier Type: -

Identifier Source: secondary_id

NCI-T99-0111

Identifier Type: -

Identifier Source: secondary_id

CDR0000067943

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02340

Identifier Type: -

Identifier Source: org_study_id