RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Combining colony-stimulating factors such as sargramostim with vaccines may kill more tumor cells. PURPOSE: Phase I trial to compare the effectiveness of vaccine therapy with or without sargramostim in treating patients who have solid tumors .

Condition	Treatment or Intervention	Phase
unspecified adult solid tumor, protocol specific	Procedure: biological response modifier therapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy  Procedure: vaccine therapy  Vaccine: recombinant viral vaccine  Drug: fowlpox-CEA-TRICOM vaccine  Drug: sargramostim  Drug: vaccinia-CEA-TRICOM vaccine	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the maximum tolerated dose of recombinant fowlpox-CEA-B7.1/ICAM-1/LFA-3 (fowlpox-CEA-TRICOM) vaccine alone or in combination with recombinant vaccinia-CEA-B7.1/ICAM-1/LFA-3 (vaccinia-CEA-TRICOM) vaccine with or without sargramostim (GM-CSF) in patients with CEA-expressing tumors. II. Determine the toxicity profile of these regimens in these patients. III. Determine the safety and impact of GM-CSF on the immunologic response in patients treated with this regimen. IV. Determine the impact of vaccine therapy on the quantity of circulating CEA-positive cells in patients treated with these regimens. V. Determine objective anti-tumor responses in patients treated with these regimens.

PROTOCOL OUTLINE: This is a dose-escalation study of fowlpox-CEA-B7.1/ICAM-1/LFA-3 vaccine and vaccinia-CEA-B7.1/ICAM-1/LFA-3 vaccine. Stage I: Patients receive fowlpox-CEA-B7.1/ICAM-1/LFA-3 vaccine subcutaneously (SC) once daily on days 1, 29, 57, and 85. Cohorts of 3-6 patients receive escalating doses of the fowlpox vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity (DLT). Stage II: Patients receive vaccinia-CEA-B7.1/ICAM-1/LFA-3 vaccine intradermally once on day 1 and fowlpox-CEA-B7.1/ICAM-1/LFA-3 vaccine SC at the MTD determined in stage I once daily on days 29, 57, and 85. Cohorts of 3-6 patients receive escalating doses of the vaccinia vaccine until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience DLT. Stage III: A single cohort of 6-10 patients receive both vaccines as in stage II, at the MTDs determined in stages I and II and sargramostim (GM-CSF) SC once daily on days 1-4, 29-32, 57-60, and 85-88. In each of the three stages, treatment repeats in the absence of disease progression or unacceptable toxicity. Patients in any stage of the study with responding disease may receive additional doses of the fowlpox vaccine monthly for 2 months and then every 3 months thereafter. Patients who have objective evidence of response (including mixed response), defined as radiographic tumor regression, and/or a fall in an elevated serum CEA level after the sixth vaccine and who subsequently develop disease progression while on the extended every 3 month treatment schedule and have no other potentially better treatment alternatives available may continue treatment as per the monthly vaccination schedule for 2 additional months. Patients with stable or responding disease after those two monthly vaccines may continue monthly vaccines at the discretion of the principal investigator.

PROJECTED ACCRUAL: Approximately 12-42 patients will be accrued for this study within 4-14 months.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed solid tumor that has failed standard therapy, has relapsed, or for which no standard therapy exists; Metastatic disease; Immunohistological evidence of CEA expression OR CEA greater than 10 at any time
• HLA-A2 positive if receiving highest dose in each regimen (required for at least 6 patients in each of 3 cohorts but not for all patients)
• Vaccinia-naive patients are eligible to enroll in any cohort
• No active brain metastasis

--Prior/Concurrent Therapy--

• Biologic therapy: No prior CEA-containing vaccination; No other concurrent immunotherapy or biologic therapy
• Chemotherapy: At least 3-4 weeks since prior cytotoxic therapy (6 weeks for nitrosoureas or mitomycin) and recovered; No concurrent chemotherapy
• Endocrine therapy: No concurrent hormonal therapy; No concurrent systemic steroids except for physiologic doses of systemic steroid replacement; Concurrent local steroids (e.g., topical, nasal, or inhaled) allowed
• Radiotherapy: No prior radiotherapy to more than 50% of all nodal groups
• Surgery: At least 21 days since prior major surgery and recovered
• Other: Recovered from prior therapy

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-1
• Life expectancy: At least 6 months
• Hematopoietic: WBC at least 3,000/mm3; Absolute neutrophil count at least 1,500/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN); SGOT and SGPT no greater than 4 times ULN
• Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 60 mL/min; No proteinuria, hematuria, or abnormal sediment unless underlying cause is non-renal
• Immunologic: HIV negative; No altered immune function, immunodeficiency, or autoimmune disease, including: 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); Addison's disease; Hashimoto's thyroiditis; Systemic lupus erythematosus; Sjogren's syndrome; Scleroderma; Myasthenia gravis; Goodpasture's syndrome; Active Graves' disease
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception during and for at least 6 months after study; No other serious concurrent medical illness (e.g., inflammatory bowel disease, Crohn's disease, ulcerative colitis, or active diverticulitis); No allergy to eggs or egg products; No allergy or untoward reaction to prior vaccination with vaccinia virus; No uncontrolled seizure disorders; No encephalitis; No multiple sclerosis; No frequent vomiting or severe anorexia; Must be maintaining a reasonable state of nutrition, consistent with weight gain; Must be able to avoid close contact with persons meeting the following criteria for at least 2 weeks after vaccination: Children under 5 years of age; Pregnant or nursing women; Individuals with prior or active eczema or other eczematoid skin disorders; Individuals with other acute, chronic, or exfoliative skin conditions (e.g., atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds) until condition resolves; Immunodeficient or immunosuppressed individuals (by disease or therapy), including HIV infection

District of Columbia
      Lombardi Cancer Center, Washington,  District of Columbia,  20007,  United States

Study chairs or principal investigators

John L. Marshall,  Study Chair,  Lombardi Cancer Research Center   

Study ID Numbers:  CDR0000068427; GUMC-00101; NCI-833; GUMC-IBC20-09; NIH/OBA-0006-405
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  February 2, 2001
ClinicalTrials.gov Identifier:  NCT00009958
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08