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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

Conditions: Adult Solid Neoplasm

Treatments: Biological: Recombinant Vaccinia-CEA(6D)-TRICOM Vaccine; Biological: Sargramostim; Biological: Recombinant Fowlpox-CEA(6D)/TRICOM Vaccine; Biological: Recombinant Interferon Alfa-2b

Study type: Interventional

Funder types: NIH

Identifiers

NCT00217373

OSU 0312 (Other Identifier)

NCI-5633

U01CA076576 (U.S. NIH Grant/Contract)

OSU-2005H0005

5633 (Other Identifier)

P30CA016058 (U.S. NIH Grant/Contract)

CDR0000439532

NCI-2011-01347 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 33 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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33 participants in 1 patient group

Arm I

Experimental group

Description:

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.

Treatment:

Biological: Recombinant Interferon Alfa-2b

Biological: Recombinant Fowlpox-CEA(6D)/TRICOM Vaccine

Biological: Sargramostim

Biological: Recombinant Vaccinia-CEA(6D)-TRICOM Vaccine