Vaccine Therapy, GM-CSF, and Interferon Alfa-2b in Treating Patients With Locally Advanced or Metastatic Cancer That Expresses Carcinoembryonic Antigen (CEA)

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

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

Phase: Phase 1

Status: Recruiting

Sponsored by: Arthur G. James Cancer Hospital & Richard J. Solove Research Institute

Official(s) and/or principal investigator(s):
William E. Carson, MD, Study Chair, Affiliation: Arthur G. James Cancer Hospital & Richard J. Solove Research Institute

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.

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

Study design: Treatment

Detailed description: 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.

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

Criteria:

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

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center, Columbus, Ohio 43210-1240, United States; Recruiting
Clinical Trials Office - OSU Comprehensive Cancer Center, Phone: 614-293-4976, Email: osu@emergingmed.com

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

Starting date: June 2006
Last updated: July 23, 2008