RATIONALE: Vaccines made from a gene-modified virus may make the body build an immune response to kill tumor cells. Colony-stimulating factors, such as sargramostim, may increase the number of immune cells found in bone marrow or peripheral blood. Combining vaccine therapy with sargramostim may cause a stronger immune response and kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving vaccine therapy together with sargramostim works in treating patients with metastatic cancer .

Condition	Treatment or Intervention	Phase
stage IV colon cancer Stage IV rectal cancer recurrent colon cancer recurrent rectal cancer unspecified adult solid tumor, protocol specific	Drug: fowlpox-CEA-MUC-1-TRICOM vaccine  Drug: sargramostim  Drug: vaccinia-CEA-MUC-1-TRICOM vaccine  Procedure: biological response modifier therapy  Procedure: non-specific immune-modulator therapy  Procedure: recombinant viral vaccine  Procedure: vaccine therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the safety and tolerability of vaccination comprising recombinant vaccinia-CEA-MUC-1-TRICOM vaccine, recombinant fowlpox-CEA-MUC-1-TRICOM vaccine, and sargramostim (GM-CSF) in patients with carcinoembryonic antigen- or MUC-1 antigen-expressing metastatic carcinoma.

Secondary

• Determine objective antitumor response in patients treated with this regimen.
• Determine immune response in patients treated with this regimen.

OUTLINE: This is a non-randomized, open-label, pilot study. Patients are stratified according to disease type (colorectal carcinoma vs noncolorectal carcinoma).

• Core phase: Patients receive recombinant vaccinia-CEA-MUC-1-TRICOM vaccine subcutaneously (SC) on day 1 and recombinant fowlpox-CEA-MUC-1-TRICOM vaccine SC on or about days 15, 29, and 43. Patients also receive sargramostim (GM-CSF) SC on days 1-4 and on or about days 15-18, 29-32, and 43-46.
• Extension phase: Patients who do not have progressive disease after the core phase receive recombinant fowlpox-CEA-MUC-1-TRICOM vaccine SC on day 1 and 29 and GM-CSF SC on days 1-4. Treatment repeats every 57 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 4 weeks for 3 months and then annually for up to 15 years.

PROJECTED ACCRUAL: A maximum of 25 patients (10 with colorectal carcinoma and 10-15 with noncolorectal carcinoma) will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal or noncolorectal carcinoma
• Metastatic disease
• Carcinoembryonic antigen (CEA)- or MUC-1 antigen-positive (≥ 20% of cells) by immunohistochemistry OR elevated CEA (> 5 μg/L) at any point during the course of disease
• Measurable or non-measurable disease
• HLA-A2 positive (all colorectal carcinoma patients)
• At least 10 patients with noncolorectal carcinoma must be HLA-A2-positive
• Completed ≥ 1 fluorouracil-containing chemotherapy regimen (e.g., fluorouracil and leucovorin calcium with or without either irinotecan or oxaliplatin) for colorectal carcinoma
• Patients with noncolorectal carcinoma must have failed OR be ineligible for therapy of proven efficacy
• No evidence of clinically active brain metastasis within the past 2 months

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• At least 4 months

Hematopoietic

• Granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• WBC ≥ 500/mm^3
• Hemoglobin ≥ 10 g/dL

Hepatic

• Bilirubin normal (≤ 3.0 mg/dL for patients with Gilbert's disease)
• AST ≤ 2 times upper limit of normal
• Hepatitis B and C negative

Renal

• Creatinine normal OR
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• No clinically significant cardiomyopathy

Immunologic

• HIV negative
• No active autoimmune disease requiring treatment OR history of autoimmune disease that may be stimulated by vaccine therapy
• No allergy or untoward reaction to prior vaccinia virus vaccine
• No altered immune function, including any of the following conditions:
• Immunodeficiency
• Eczema or other eczematoid skin disorders
• Acute, chronic, or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds)
• No serious hypersensitivity reaction to egg products
• No inflammatory eye condition that may require medication during study treatment
• No active infection with fever > 100°F

Gastrointestinal

• No inflammatory bowel disease
• No Crohn's disease
• No ulcerative colitis
• No active diverticulitis

Other

• Endocrine disease, including thyroid disease, adrenal disease, and vitiligo, that is controlled by replacement therapy allowed
• No close household contact (sharing housing or having close physical contact) with the following individuals for 3 weeks after each vaccination:
• Individuals with active or history of eczema or other eczematoid skin disorders
• Individuals with other unresolved acute, chronic, or exfoliative skin disorders (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds)
• Pregnant or nursing women
• Children under 5 years of age
• Immunodeficient or immunosuppressed individuals (by disease or therapy), including HIV-positive individuals
• No other serious medical condition that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 months after completion of study treatment

PRIOR CONCURRENT THERAPY: Biologic therapy

• Prior immunotherapy with related vaccinia or fowlpox vaccines or antigen-specific peptides allowed
• No other concurrent anticancer immunotherapy

Chemotherapy

• See Disease Characteristics
• At least 6 weeks since prior nitrosoureas or mitomycin
• No concurrent chemotherapy

Endocrine therapy

• No concurrent systemic steroids except physiologic doses for systemic steroid replacement OR local (topical, nasal, or inhaled) steroid use
• No steroid eye drops for 2 weeks before until 4 weeks after initial vaccinia vaccination
• No concurrent anticancer hormonal therapy
• Patients with prostate cancer who have not undergone orchiectomy must continue gonadotropin-releasing hormone agonist therapy

Radiotherapy

• No concurrent radiotherapy

Surgery

• No concurrent major surgery

Other

• Recovered from all prior therapy
• More than 72 hours since prior antibiotics
• No other concurrent antineoplastic therapy

Maryland
      National Naval Medical Center, Bethesda,  Maryland,  20889,  United States; Recruiting
      Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support, Bethesda,  Maryland,  20892-1182,  United States; Recruiting

Study chairs or principal investigators

James Gulley, MD, PhD,  Principal Investigator,  National Cancer Institute (NCI)   

Study ID Numbers:  CDR0000381300; NCI-04-C-0246; NCI-6536; NCT00091000
Record last reviewed:  March 2005
Last Updated:  April 5, 2005
Record first received:  September 7, 2004
ClinicalTrials.gov Identifier:  NCT00091000
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08