Vaccine Therapy in Treating Patients With Metastatic Solid Tumors

Condition(s) targeted: Unspecified Adult Solid Tumor, Protocol Specific

Intervention: recombinant fowlpox-B7.1 vaccine (Drug); recombinant fowlpox-TRICOM vaccine (Drug); recombinant viral vaccine therapy (Procedure)

Phase: Phase 1

Status: Active, not recruiting

Sponsored by: Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

Official(s) and/or principal investigator(s):
Howard L. Kaufman, MD, Study Chair, Affiliation: Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Infusing the vaccine directly into a tumor may cause a stronger immune response and kill more tumor cells. It is not yet known which vaccine may be more effective in treating metastatic solid tumors. PURPOSE: Randomized phase I trial to compare the effectiveness of two different vaccines given directly into the tumor in treating patients who have metastatic solid tumors.

Official title: Intra-Lesional rF-B7.1 Versus rF-Tricom Vaccine In The Treatment Of Metastatic Cancer

Study design: Treatment, Randomized, Active Control

Primary outcome: Safety by CTC every 2 weeks

Secondary outcome:

Immune response as assessed by ELISPOT assay at 2 weeks following course 3 and at 3 months

Objective response rate by RECIST at 2 weeks following course 3 and at 3 months

Detailed description: OBJECTIVES: Compare the feasibility of intratumoral administration of rF-B7. 1 vaccine vs recombinant fowlpox-TRICOM vaccine in patients with cutaneous, subcutaneous, or lymph node metastatic solid tumors. Compare the feasibility of intratumoral administration of these vaccines in patients with visceral metastatic solid tumors. Compare the clinical toxicity of these vaccines in these patients. Determine the optimal dose of these vaccines in these patients. Compare the clinical response of patients treated with these vaccines. Compare the safety profiles of these vaccines in these patients. Determine the quality of life of patients treated with these vaccines. Determine the anti-tumor immune reactivity in patients treated with these vaccines. OUTLINE: This is a randomized study with dose-escalation component. Patients are stratified according to tumor location (cutaneous, subcutaneous, or lymph node metastases vs visceral metastases). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive rF-B7. 1 vaccine intratumorally on day 1. Arm II: Patients receive fowlpox-TRICOM vaccine intratumorally on day 1. Treatment in both arms repeats every 4 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may receive additional courses. Three patients from the cutaneous disease (CD) stratum are treated at low-dose in each treatment arm. If no more than 1 of 6 patients experience dose-limiting toxicity (DLT), then 6 additional CD patients are randomized to high-dose treatment. If no more than 1 of these 6 patients experience DLT, then 12 patients from the visceral disease (VD) stratum are randomized to low-dose treatment. If no more than 2 of 12 VD patients experience DLT, then the next cohort of 12 VD patients is randomized to high-dose treatment. If 3 of the original 12 VD patients experience DLT, then 6 additional VD patients receive low-dose treatment. If no more than 3 of 18 patients experience DLT, then 12 VD patients receive high-dose treatment. Quality of life is assessed at baseline, monthly during therapy, and then at the end of therapy. Patients are followed every 3 months. PROJECTED ACCRUAL: A total of 42 patients (21 per treatment arm; 12 in the cutaneous stratum and 30 in the visceral stratum) will be accrued for this study within 1-2 years.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

DISEASE CHARACTERISTICS: Histologically confirmed metastatic unresectable solid tumors Cutaneous, subcutaneous, lymph node, or visceral tumors that are accessible to imaging and injections No standard therapy available At least 1 unidimensionally measurable lesion At least 20 mm for visceral lesions At least 10 mm for cutaneous, subcutaneous, and nodal lesions No untreated or edematous metastatic brain lesions At least 6 weeks since prior surgery and/or radiotherapy for brain metastases and no evidence of disease or edema on CT scan or MRI No ascites or pleural effusions No leptomeningeal disease PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-1 Life expectancy: More than 3 months Hematopoietic: Absolute granulocyte count at least 3,000/mm^3 Platelet count at least 100,000/mm^3 No bleeding diathesis Hepatic: Bilirubin no greater than 1. 5 mg/dL* SGOT/SGPT no greater than 2 times upper limit of normal (ULN)* Alkaline phosphatase no greater than 2 times ULN* No elevated PT or PTT No cirrhosis No active hepatitis No hepatic insufficiency NOTE: * Unless due to metastases Renal: Creatinine no greater than 2. 0 mg/dL No renal insufficiency Pulmonary: No chronic obstructive pulmonary disorder Immunologic: No active autoimmune disorders No active immunologically mediated disease (e. g., severe psoriasis, colitis, idiopathic thrombocytopenic purpura, multiple sclerosis, connective tissue disease, or active rheumatoid arthritis) No significant allergy or hypersensitivity to eggs Other: No active seizure disorder No active or chronic infections No other significant medical disease that would preclude study participation No other malignancy within the past 5 years except stage I cervical cancer or basal cell carcinoma Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: More than 8 weeks since prior immunotherapy and recovered Chemotherapy: More than 4 weeks since prior chemotherapy and recovered Endocrine therapy: At least 4 weeks since prior systemic corticosteroids No concurrent corticosteroids Radiotherapy: See Disease Characteristics More than 2 weeks since prior radiotherapy and recovered No evidence of bone marrow toxicity from prior radiotherapy Surgery: See Disease Characteristics More than 4 weeks since prior surgery and recovered

Herbert Irving Comprehensive Cancer Center at Columbia University, New York, New York 10032, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: January 2002
Last updated: December 25, 2007