Vaccine Therapy in Treating Patients With Metastatic Melanoma

National Cancer Institute (NCI)

Status and phase

Terminated

Phase 2

Conditions

Recurrent Melanoma

Stage IV Melanoma

Treatments

Biological: recombinant fowlpox-TRICOM vaccine

Other: laboratory biomarker analysis

Study type

Interventional

Funder types

NIH

Identifiers

NCT00087373

NCI-6038

12759A (Other Identifier)

6038 (Other Identifier)

UCCRC-12759A

P30CA014599 (U.S. NIH Grant/Contract)

NCI-2012-02615 (Registry Identifier)

CDR0000374979

Details and patient eligibility

About

Vaccines may make the body build an immune response to kill tumor cells. Injecting a vaccine directly into a tumor may cause a stronger immune response and kill more tumor cells. This phase II trial is studying how well vaccine therapy works in treating patients with metastatic melanoma.

Full description

PRIMARY OBJECTIVES:

I. Determine the safety and tolerability of intratumoral fowlpox-TRICOM in patients with metastatic melanoma.

II. Determine the local response rate in patients treated with this agent. III. Determine systemic clinical response in patients treated with this agent.

SECONDARY OBJECTIVES:

I. Determine the increase in transgene expression of B7-1, leukocyte function-associated antigen-3 (LFA-3), and intercellular adhesion molecule-1 (ICAM-1) in patients treated with this agent.

II. Determine the effects of this agent on CD8-positive antitumor T-cell frequency as measured by tetramer and ELISpot in patients who are HLA-A2 positive.

III. Correlate transgene expression of B7-1, LFA-3, and ICAM-1 by tumor cells with changes in function or number of melanoma antigen-specific CD8-positive T lymphocytes in patients treated with this agent.

OUTLINE: This is a multicenter study.

Patients receive fowlpox-TRICOM intratumorally on day 1 of weeks 1, 4, and 7 (maximum of 3 injections for a single lesion) (course 1). After 3 injections (course 1), patients with stable or responding disease receive additional injections into new lesions following the same schedule as above. Treatment repeats every 9 weeks for a maximum total of 9 injections (3 injections total into a maximum of 3 different tumors) (total of 3 courses) in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months until disease progression and then approximately every 6 months for 5-15 years.

PROJECTED ACCRUAL: A total of 14-28 patients will be accrued for this study within 14-28 months.

Enrollment

28 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Histologically or cytologically confirmed melanoma
- Stage IV disease
Measurable disease
- At least 1 cutaneous or lymph node mass ≥ 1 cm AND amenable to biopsy and percutaneous injection AND can be accurately measured with standard calipers
Must be tested for expression of HLA-A2 prior to study
Must have 1 of the following criteria:
- Circulating melanoma-specific CD8-positive T cells against ≥ 1 defined antigen (Melan-A, gp100 antigen, tyrosinase, MAGE-A10, Trp-2, or NA17) as measured by tetramer or ELISpot directly ex-vivo or after a 10 day in vitro expansion
- Detectable intratumoral T cells measured in the index lesion that is to be injected with rF-TRICOMTM by immunohistochemistry (IHC) for CD4, CD8 or another T cell marker, or by real time RT-PCR for CD8a, CD4, or other T cell transcripts
No untreated or edematous brain metastases or leptomeningeal disease
- Treated CNS disease allowed provided patient remains stable off corticosteroid therapy
Performance status - Karnofsky 70-100%
More than 12 weeks
WBC ≥ 3,000/mm^3
Platelet count ≥ 100,000/mm^3
No uncontrolled bleeding disorder that would increase the risk of bleeding from the injected lesion
No active thrombotic thrombocytopenic purpura within the past 2 years
PT/PTT ≤ 1.25 times upper limit of normal (ULN)
AST and ALT ≤ 1.5 times ULN
Bilirubin ≤ 1.5 times ULN
No chronic hepatitis B or C
Creatinine ≤ 2.0 mg/dL
Creatinine clearance ≥ 60 mL/min
No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia
HIV negative
No prior significant allergic reaction or hypersensitivity to eggs or egg products
No disease that limits the function of the spleen (e.g., sickle cell disease)
No uncontrolled active or chronic infection
No active autoimmune disorders or disease
No immunosuppression, defined as concurrent or possible requirement for systemic corticosteroids
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for at least 4 weeks after study participation
Able to avoid direct contact of the immunization site with the following individuals:
- Children < 3 years of age
- Immunocompromised individuals (including those on systemic corticosteroids)
- Pregnant women
- Individuals with extensive skin disease
No active seizure disorder
No skin disease and/or open unhealing wounds
No psychiatric illness or social situation that would preclude study compliance
No other significant medical illness that would significantly increase the risk associated with immunotherapy
No other active malignancy requiring concurrent therapy except squamous cell or basal cell skin cancer or undetectable hormone-responsive prostate cancer (as measured by normal prostate-specific antigen)
No other concurrent uncontrolled illness that would preclude study participation
No prior fowlpox virus-based therapy
No prior B7-1, intercellular adhesion molecule-1 (ICAM-1), or leukocyte function-associated antigen-3 (LFA-3)
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
See Disease Characteristics
Concurrent adjuvant hormonal therapy for early-stage or high-risk breast cancer allowed
No concurrent corticosteroids
More than 2 weeks since prior radiotherapy and recovered
More than 2 weeks since prior surgery and recovered
No prior splenectomy
No concurrent therapeutic anticoagulation therapy that would increase the risk of bleeding from injected lesion
No other concurrent immunosuppressive drugs
No other concurrent investigational agents
No other concurrent anticancer therapy