Vaccine Therapy in Treating Patients With Stage IV Melanoma

NCT ID: NCT00033228

Last Updated: 2011-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-01-31
• Study Completion Date: 2003-04-30

Brief Summary

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Infusing the vaccine directly into a lymph node may cause a stronger immune response and kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy in treating patients who have stage IV melanoma.

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose of intranodal Synchrovax SEM plasmid DNA vaccine in patients with stage IV melanoma.
• Determine the safety and tolerability of this drug in these patients.
• Determine the immunological response, as measured by changes in frequency of T cells specific against vaccine-encoded epitopes before and after treatment, in patients treated with this drug.
• Determine the clinical response, as measured by lactic dehydrogenase levels and radiologic assessment of lesions, in patients treated with this drug.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive Synchrovax SEM plasmid DNA vaccine by continuous intranodal infusion on days 1-4. Treatment repeats every 14 days for up to 4 courses in the absence of unacceptable toxicity. Patients with evidence of stable or responding disease are eligible for 4 additional courses of treatment.

Cohorts of 6 patients receive escalating doses of Synchrovax SEM plasmid DNA vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at 10 days after the last dose of study drug.

PROJECTED ACCRUAL: A total of 6-18 patients will be accrued for this study.

Conditions

Melanoma (Skin)

Study Design

• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

The first cohort of 6 patients received 500 ug of Synchrovax SEM plasmid DNA vaccine. All patients were to be monitored for dose limiting toxicities DLTs) for a minimum of 2 weeks after their second infusion of vaccine on Day 15 before allowing patients to enroll at the next dose group. The decision to progress to the next dose group was to be based on occurrence of DLTs observed in 1 or fewer (\<33%) patients of a 6 patient cohort.

Group Type: EXPERIMENTAL

MKC1106-MT

Intervention Type: BIOLOGICAL

Cancer Vaccine, Immunotherapy, 500 ug

Cohort 2

The second cohort of 6 patients received 1000 ug of Synchrovax SEM plasmid DNA vaccine. All patients were to be monitored for dose limiting toxicities DLTs) for a minimum of 2 weeks after their second infusion of vaccine on Day 15 before allowing patients to enroll at the next dose group. The decision to progress to the next dose group was to be based on occurrence of DLTs observed in 1 or fewer (\<33%) patients of a 6 patient cohort.

Group Type: EXPERIMENTAL

MKC1106-MT

Intervention Type: BIOLOGICAL

Cancer Vaccine, Immunotherapy, 1000 ug

Cohort 3

The third cohort of 6 patients received 1500 ug of Synchrovax SEM plasmid DNA vaccine. The maximum tolerated dose (MTD) was to be determined by the observation of DLT at each dose group.

Group Type: EXPERIMENTAL

MKC1106-MT

Intervention Type: BIOLOGICAL

Cancer Vaccine, Immunotherapy, 1500 ug

Interventions

MKC1106-MT

Cancer Vaccine, Immunotherapy, 500 ug

Intervention Type: BIOLOGICAL

MKC1106-MT

Cancer Vaccine, Immunotherapy, 1000 ug

Intervention Type: BIOLOGICAL

MKC1106-MT

Cancer Vaccine, Immunotherapy, 1500 ug

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed stage IV melanoma
• Must have tumor tissue available for determining antigen expression

• At least 10% of tumor cells must stain positive for Melan-A/Mart-1 by immunohistochemistry
• HLA-A2 positive
• No brain metastases unless completely resected or without evidence of disease after treatment

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• More than 3 months

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm3
• WBC at least 3,000/mm3
• Platelet count at least 75,000/mm3
• Hemoglobin at least 9 g/dL

Hepatic:

• SGOT and SGPT no greater than 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 2.5 times ULN
• Bilirubin no greater than 1.5 times ULN
• Hepatitis B surface antigen negative
• Hepatitis C antibody negative

Renal:

• Creatinine no greater than 1.5 times ULN
• Urea no greater than 2.6 times ULN

Other:

• Not pregnant, nursing, or planning to become pregnant within 6 months of treatment completion
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• No medical, sociological, or psychological impediments that would preclude study

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• At least 4 weeks since prior immunotherapy
• At least 4 weeks since prior immunomodulatory drugs
• No other concurrent immunotherapy
• No concurrent immunomodulatory drugs

Chemotherapy:

• At least 4 weeks since prior chemotherapy
• No concurrent chemotherapy

Endocrine therapy:

• At least 4 weeks since prior systemic corticosteroids
• No concurrent systemic corticosteroids

Radiotherapy:

• At least 4 weeks since prior radiotherapy
• No concurrent radiotherapy

Surgery:

• See Disease Characteristics

Other:

• At least 4 weeks since prior investigational drugs
• No other concurrent investigational drugs

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

Sponsors

Mannkind Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Mannkind Coorporation

Principal Investigators

Chief Scientific Officer

Role: STUDY_CHAIR

Mannkind Corporation

Locations

Arizona Cancer Center at University of Arizona Health Sciences Center

Tucson, Arizona, United States

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

Cancer Research Center at Boston Medical Center

Boston, Massachusetts, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Earle A. Chiles Research Institute at Providence Portland Medical Center

Portland, Oregon, United States

Countries

United States

Other Identifiers

CTL-26-35

Identifier Type: -

Identifier Source: secondary_id

CDR0000069252

Identifier Type: -

Identifier Source: org_study_id