Official Title: “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”

RATIONALE: 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.

PURPOSE: 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.

Study Type: Interventional

Study Design: Treatment

Study Primary Completion Date: August 2007

OBJECTIVES:

Primary - 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 - Determine the effect of IFN-α-2b on tumor cell expression of CEA and MHC class I antigens in patients treated with this regimen. - Determine the immunologic effects of this regimen in these patients. - Determine any objective anti-tumor responses that may occur in response to this regimen in these patients. - 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 1: 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 2-4: 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.

PROJECTED ACCRUAL: A minimum of 27 patients will be accrued for this study within 8-10 months.

Intervention(s) in this Clinical Trial

• Drug: recombinant fowlpox-CEA(6D)/TRICOM vaccine
• Drug: recombinant interferon alfa-2b
• Drug: recombinant vaccinia-CEA(6D)-TRICOM vaccine
• Drug: sargramostim

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

• Age
• 18 and over
• Performance status
• ECOG 0-2 OR
• Karnofsky 60-100%
• Life expectancy
• More than 6 months
• Hematopoietic
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hepatic
• Bilirubin ≤ 2.0 times upper limit of normal (ULN)
• AST and ALT ≤ 4.0 times ULN
• Hepatitis B negative
• Hepatitis C negative
• Renal
• Creatinine ≤ 1.96 mg/dL OR
• Creatinine clearance > 50 mL/min
• No persistent proteinuria*
• Protein < 1,000 mg by 24-hour urine collection*
• No urinary sediment abnormalities* NOTE: *Proteinuria, urinary sediment abnormalities, or hematuria allowed if found to be, after evaluation, nonrenal in origin or to represent renal changes that are stable and unlikely to progress during course of vaccination
• Cardiovascular
• 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
• Immunologic
• 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
• Other
• 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
• 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)

PRIOR CONCURRENT THERAPY:

• Biologic therapy
• No concurrent influenza vaccine
• Chemotherapy
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• Endocrine therapy
• No concurrent steroid therapy, except topical or inhaled steroids
• No concurrent steroid eye drops
• Radiotherapy
• More than 4 weeks since prior radiotherapy and recovered
• Surgery
• More than 4 weeks since prior surgery and recovered
• No prior splenectomy
• Other
• No other concurrent investigational agents

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Arthur G. James Cancer Hospital & Richard J. Solove Research Institute

Overall Clinical Trial Officials and Contacts

William E. Carson, MD Study Chair Arthur G. James Cancer Hospital & Richard J. Solove Research Institute  

Information obtained from ClinicalTrials.gov on September 04, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00217373

Study ID Number: CDR0000439532

ClinicalTrials.gov Identifier: NCT00217373

Health Authority: Unspecified

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