vaccine therapy, gm-csf, and interferon alfa-2b in treating patients with locally advanced or metastatic cancer that expresses carcinoembryonic antigen (cea)

Conditions: Adult Solid Neoplasm

Summary: 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.

Eligibility criteria:
inclusion criteria: * histologically confirmed carcinoembryonic antigen (cea)-expressing carcinoma * metastatic or locally advanced disease * 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: * burns * impetigo * varicella zoster * severe acne * other open wounds or rashes * 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 * no sexual contact for 3 weeks after each vaccination 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: * history of or active eczema or other eczematoid skin disorders * atopic dermatitis * other acute, chronic, or exfoliative skin conditions (e.g., burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds) * 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