A Phase I Study of Sequential Vaccinations With Fowlpox-CEA(6D)-Tricom (B7.1/ICAM/LFA3) and Vaccinia-CEA (6D)-Tricom, in Combination With GM-CSF and Interferon-Alfa-2B in Patients With CEA-Expressing Carcinomas
A Phase I Study of Sequential Vaccinations With Fowlpox-CEA(6D)-Tricom (B7.1/ICAM/LFA3) and Vaccinia-CEA (6D)-Tricom, in Combination With GM-CSF and Interferon-Alfa-2B in Patients With CEA-Expressing Carcinomas
This phase I trial is studying the side effects and best dose of interferon alfa-2b when given together with vaccine therapy and GM-CSF in treating patients with locally advanced or metastatic cancer that makes CEA. Vaccines made from a gene-modified virus may help the body build an effective immune response to kill cancer cells that make carcinoembryonic antigen (CEA). Biological therapies, such as GM-CSF, may stimulate the immune system in different ways and stop cancer cells from growing. Interferon alfa-2b may interfere with the growth of cancer cells and slow cancer growth. Giving vaccine therapy together with GM-CSF and interferon alfa-2b may kill more cancer cells that make CEA.
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose and recommended phase II dose of interferon alfa-2b (IFN-α-2b) when administered with recombinant vaccinia-CEA(6D)-TRICOM vaccine, recombinant fowlpox-CEA(6D)-TRICOM vaccine, and sargramostim (GM-CSF) in patients with locally advanced or metastatic carcinoembryonic antigen (CEA)-expressing carcinoma.
SECONDARY OBJECTIVES:
I. Determine the effect of IFN-α-2b on tumor cell expression of CEA and MHC class I antigens in patients treated with this regimen.
II. Determine the immunologic effects of this regimen in these patients. III. Determine any objective anti-tumor responses that may occur in response to this regimen in these patients.
IV. Determine the time to tumor progression in patients treated with this regimen.
OUTLINE: This is a dose-escalation study of interferon alfa-2b (IFN-α-2b).
COURSE I: Patients receive recombinant vaccinia-CEA(6D)-TRICOM vaccine subcutaneously (SC) on day 1. Patients also receive sargramostim (GM-CSF) SC on days 1-4 and IFN-α-2b* SC on days 9, 11, and 13.
COURSES II-IV: Patients receive recombinant fowlpox-CEA(6D)-TRICOM vaccine SC on day 1. Patients also receive GM-CSF as in course 1 and IFN-α-2b* SC on days 1, 3, and 5.
NOTE: *The initial cohort of 6 patients does not receive IFN-α-2b.
Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. After 4 courses, patients who do not have progressive disease or unacceptable toxicity may receive recombinant fowlpox-CEA (6D)-TRICOM vaccine, GM-CSF, and IFN-α-2b every 28 days for 2 more courses and then every 3 months for up to 2 years.
Cohorts of 3-6 patients receive escalating doses of IFN-α-2b until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Six additional patients are treated at the MTD; these patients must be HLA-A2 positive.
After completion of study treatment, patients are followed monthly for 4 months and then every 6-12 months for up to 15 years.
Inclusion Criteria:
Histologically confirmed carcinoembryonic antigen (CEA)-expressing carcinoma
Tumor accessible for biopsy
Must have received ≥ 1 prior systemic regimen for metastatic disease
No known brain metastases
Performance status - ECOG 0-2
Performance status - Karnofsky 60-100%
More than 6 months
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Bilirubin ≤ 2.0 times upper limit of normal (ULN)
AST and ALT ≤ 4.0 times ULN
Hepatitis B negative
Hepatitis C negative
Creatinine ≤ 1.96 mg/dL
Creatinine clearance > 50 mL/min
No persistent proteinuria
Protein < 1,000 mg by 24-hour urine collection
No urinary sediment abnormalities
No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia
No clinically significant cardiomyopathy requiring treatment
No impaired function (i.e., ejection fraction < 50%) for patients who have not had prior vaccine and are asymptomatic
HIV negative
No ongoing or active infection
No history of allergic reaction to eggs or egg products
No history of allergy or untoward reaction to prior vaccinia vaccination (e.g., smallpox immunization) or to any of its components
No history of or active eczema or other eczematoid skin disorders
No atopic dermatitis
No other acute, chronic, or exfoliative skin conditions, including any of the following:
No immunocompromised condition
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
Must be willing to undergo tumor biopsy
No psychiatric illness or social situation that would preclude study compliance
No life-threatening illness
No other active malignancy within the past 2 years except nonmelanoma skin cancer or superficial bladder or cervical lesions treated with surgical resection
No other uncontrolled illness
Must be able to avoid close household contact with the following individuals for ≥ 3 weeks after vaccinia vaccination:
Pregnant or nursing women
Children under 5 years of age
Individuals who are immunodeficient or immunosuppressed by disease or therapy (including HIV infection)
Individuals with the following conditions:
No concurrent influenza vaccine
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
No concurrent steroid therapy, except topical or inhaled steroids
No concurrent steroid eye drops
More than 4 weeks since prior radiotherapy and recovered
More than 4 weeks since prior surgery and recovered
No prior splenectomy
No other concurrent investigational agents