Vaccine Therapy in Treating Patients With Unresectable Metastatic Melanoma

National Cancer Institute (NCI)

Status and phase

Completed

Phase 1

Conditions

Melanoma (Skin)

Treatments

Biological: recombinant vaccinia-B7.1 vaccine

Study type

Interventional

Funder types

NIH

Identifiers

NCT00004148

AECM-99-101

CDR0000067380

NCI-T99-0006

Details and patient eligibility

About

Phase I trial to study the effectiveness of vaccine therapy in treating patients who have unresectable metastatic melanoma. Vaccines may make the body build an immune response to kill tumor cells.

Full description

OBJECTIVES:

I. Determine the maximum tolerated dose of the rV-B7.1 vaccine that elicits a host immune response and is associated with acceptable toxicity in patients with malignant metastatic melanoma.

II. Determine all clinical toxicities associated with this regimen in this patient population.

III. Determine the safety of this regimen in this patient population. IV. Assess evidence of host antimelanoma immune reactivity following this regimen.

V. Determine the effect of this regimen on T-cell immunity. VI. Assess the clinical response in this patient population receiving this regimen.

VII. Evaluate quality of life of these patients during this regimen.

OUTLINE: This is a dose escalation study.

Patients receive rV-B7.1 intralesionally every 4 weeks for 8 weeks (weeks 0, 4, and 8). Treatment continues every 12 weeks in the absence of unacceptable toxicity or disease progression for up to 2 courses. Cohorts of 6-8 patients receive escalating doses of vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 or 3 of 8 patients experience dose limiting toxicities.

Quality of life is assessed before treatment, every 4 weeks, and at end of treatment. Patients are followed every 3 months.

Enrollment

12 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically proven metastatic, unresectable melanoma Dermal, subcutaneous, or lymph node metastases
Accessible for injection
Lesions must measure at least 1 cm
Patients with no prior treatment allowed
Patients must have one of the following as proof of prior vaccinia immunization:
- Physician certification
- Recollection and appropriate vaccination scar site
- No encephalitis, untreated cerebral metastases, other structural brain lesions, or leptomeningeal disease
- No ascites or pleural effusions
- No leukemia or lymphoma

PATIENT CHARACTERISTICS:

Age: Over 18
Performance status: ECOG 0-1 Karnofsky 80-100%
Life expectancy: Greater than 3 months
WBC greater than 4,000/mm3
Platelet count greater than 100,000/mm3
Hemoglobin greater than 10g/dL
Bilirubin less than 1.5 mg/dL
Transaminases no greater than 2 times upper limit of normal (ULN)
Alkaline phosphatase no greater than 2 times ULN
PT/PTT no greater than 2 fold elevation in patients not receiving anticoagulation medications
No alcoholic cirrhosis
Creatinine less than 2.0 mg/dL OR creatine clearance greater than 60 mL/min
No congestive heart failure
No serious cardiac arrhythmias
No recent prior myocardial infarction
No clinical coronary artery disease
No chronic obstructive pulmonary disease
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No seizure disorders
No underlying immunosuppressive disorder
No autoimmune disease HIV negative
No skin diseases
No open wounds
No eczema or other contraindications to vaccinia virus administration
Patients must be able to avoid high risk individuals (e.g., immunosuppressed patients, children under 3 years, pregnant women, patients with active or a history of eczema, or patients with other skin conditions) for 7-10 days following treatment
No significant allergy or hypersensitivity to eggs
No active or chronic infections
No concurrent medical illness
No other significant medical disease which would increase risk to patient
No other prior malignancy within the past 5 years except stage I carcinoma of the cervix or basal cell carcinoma

PRIOR CONCURRENT THERAPY:

At least 8 weeks since prior immunotherapy and recovered
No prior live pox virus vector
No more than 2 prior chemotherapy regimens
At least 4 weeks since prior chemotherapy and recovered
At least 4 weeks since prior systemic corticosteroids
No systemic corticosteroids for concurrent illness
No concurrent immunosuppressive steroids
At least 2 weeks since prior radiotherapy and recovered (no bone marrow toxicity)
At least 6 months since prior radiotherapy for brain metastases and recovered
At least 4 weeks since prior surgery for management of the primary or metastatic lesions and recovered with remaining measurable disease
At least 6 months since prior surgery for brain metastases and recovered
No concurrent immunosuppressive drugs