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

NCT ID: NCT00217373

Last Updated: 2015-04-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-06-30
• Study Completion Date: 2015-03-31

Brief 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.

Detailed Description

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.

Conditions

Adult Solid Neoplasm

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

COURSE I: Patients receive recombinant vaccinia-CEA(6D)-TRICOM vaccine 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.

Group Type: EXPERIMENTAL

Recombinant Fowlpox-CEA(6D)/TRICOM Vaccine

Intervention Type: BIOLOGICAL

Given SC

Recombinant Interferon Alfa-2b

Intervention Type: BIOLOGICAL

Given SC

Recombinant Vaccinia-CEA(6D)-TRICOM Vaccine

Intervention Type: BIOLOGICAL

Given SC

Sargramostim

Intervention Type: BIOLOGICAL

Given SC

Interventions

Recombinant Fowlpox-CEA(6D)/TRICOM Vaccine

Given SC

Intervention Type: BIOLOGICAL

Recombinant Interferon Alfa-2b

Given SC

Intervention Type: BIOLOGICAL

Recombinant Vaccinia-CEA(6D)-TRICOM Vaccine

Given SC

Intervention Type: BIOLOGICAL

Sargramostim

Given SC

Intervention Type: BIOLOGICAL

Other Intervention Names

fowlpox-CEA-B7.1/ICAM-1/LFA-3; Recombinant Fowlpox-CEA-TRICOM Vaccine; rF-CEA(6D)TRICOM; Alfatronol; Glucoferon; Heberon Alfa; IFN alpha-2B; Interferon alfa 2b; INTERFERON ALFA-2B; Interferon Alpha-2b; Intron A; Sch 30500; Urifron; Viraferon; rV-CEA(6D)-TRICOM; Vaccinia-CEA-TRICOM Vaccine; 23-L-Leucinecolony-Stimulating Factor 2; DRG-0012; Leukine; Prokine; rhu GM-CFS; Sagramostim; Sargramostatin

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William Carson

Role: PRINCIPAL_INVESTIGATOR

Ohio State University Comprehensive Cancer Center

Locations

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Countries

United States

Other Identifiers

NCI-2011-01347

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-5633

Identifier Type: -

Identifier Source: secondary_id

OSU-2005H0005

Identifier Type: -

Identifier Source: secondary_id

CDR0000439532

Identifier Type: -

Identifier Source: secondary_id

OSU 0312

Identifier Type: OTHER

Identifier Source: secondary_id

5633

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA016058

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA076576

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-01347

Identifier Type: -

Identifier Source: org_study_id