Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Active	18 and over	NCI	OSU-2005H0005 0312, 5633, NCI-5633, NCT00217373

Objectives

Primary

1. 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

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

Entry 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

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

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/mm³
• Platelet count ≥ 100,000/mm³

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)

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

William Carson, MD, Protocol chair		Ph: 614-293-6306 Email: william.carson@osumc.edu

U.S.A.
Ohio
	Columbus
	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
		Ohio State University Cancer Clinical Trial Matching Service	Ph:  866-627-7616
			Email: osu@emergingmed.com

Registry Information
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
Trial Start Date		2006-06-26
Trial Completion Date		2007-08-05 (estimated)
Registered in ClinicalTrials.gov		NCT00217373
Date Submitted to PDQ		2005-07-01
Information Last Verified		2006-11-14
NCI Grant/Contract Number		CA16058, CA76576