Official Title: “Phase I Study Of Sequential Vaccinations With Fowlpox-CEA(6D)-Tricom(B7.1/ICAM/LFA3)Alone, And In Combination With Vaccinia-CEA(6D)-Tricom, And The Role Of GM-CSF, In Patients With CEA Expressing Carcinomas”

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.

Study Type: Interventional

Study Design: Treatment

OBJECTIVES: I. Determine the maximum tolerated dose of recombinant fowlpox-CEA-TRICOM vaccine alone or in combination with recombinant 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.

OUTLINE: This is a dose-escalation study of fowlpox-CEA-TRICOM (fCEA-TRI) vaccine and vaccinia-CEA-TRICOM (vCEA-TRI) vaccine. Stage I: Patients receive fCEA-TRI vaccine subcutaneously (SC) once daily on days 1, 29, 57, and 85. Cohorts of 3-10 patients receive escalating doses of the fCEA-TRI 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 vCEA-TRI vaccine intradermally once on day 1 and fCEA-TRI vaccine SC at the MTD determined in stage I once daily on days 29, 57, and 85. Cohorts of 3-10 patients receive escalating doses of the vCEA-TRI 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. Patients in any stage of the study with responding disease may receive additional doses of the fCEA-TRI vaccine monthly for 2 months and then every 3 months thereafter. Patients who have objective evidence of response (including mixed response) 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. Patients are followed at 4 weeks and then monthly for 3 months.

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

Intervention(s) in this Clinical Trial

• Drug: recombinant fowlpox-CEA(6D)/TRICOM vaccine
• Drug: recombinant vaccinia-CEA(6D)-TRICOM vaccine
• Drug: sargramostim

• 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 allowed No active brain metastasis
• 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 prior or concurrent 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 Gastrointestinal: No inflammatory bowel disease No Crohn's disease No ulcerative colitis No active diverticulitis No frequent vomiting or severe anorexia Neurological: No uncontrolled seizure disorders No encephalitis No multiple sclerosis 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 that would preclude study No allergy to eggs or egg products No allergy or untoward reaction to prior vaccination with vaccinia virus Must be maintaining a reasonable state of nutrition, consistent with weight maintenance Must be able to avoid close household 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
• PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics 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) 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 Other: Recovered from prior therapy

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Lombardi Cancer Research Center

Overall Clinical Trial Officials and Contacts

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

Information obtained from ClinicalTrials.gov on January 06, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00009958

Study ID Number: CDR0000068427

ClinicalTrials.gov Identifier: NCT00009958

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database