RATIONALE: Vaccines 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. Interleukin-2 may stimulate a person's white blood cells to kill cancer cells. Combining vaccine therapy, sargramostim, and interleukin-2 may kill more cancer cells. PURPOSE: Randomized phase II trial to study the effectiveness of vaccine therapy, sargramostim, and interleukin-2 in treating patients who have advanced tumors.

Condition	Treatment or Intervention	Phase
stage IIIB non-small cell lung cancer stage III pancreatic cancer stage IV breast cancer stage IIIA non-small cell lung cancer stage III gastric cancer stage IV gastric cancer stage III esophageal cancer stage IVB pancreatic cancer stage IIIB breast cancer stage II pancreatic cancer stage II esophageal cancer stage IVA pancreatic cancer stage IIIA breast cancer unspecified adult solid tumor, protocol specific	Drug: ALVAC-CEA vaccine  Drug: interleukin-2  Drug: sargramostim  Drug: vaccinia-CEA vaccine	Phase II

Further Study Details: 

OBJECTIVES: I. Evaluate the safety of sequentially administered vaccinia-carcinoembryonic antigen (CEA) vaccine and ALVAC-CEA vaccine (CEA-Avipox vaccine) in two schedules and with the addition of sargramostim (GM-CSF) plus or minus interleukin-2 (IL-2) in patients with CEA expressing tumors. II. Compare the CEA-specific cellular immune response in cancer patients randomized to receive a single vaccination with vaccinia-CEA vaccine followed by three boosts with ALVAC-CEA vaccine (V-A-A-A) or the reverse vaccination sequence (A-A-A-V). III. Determine whether the addition of GM-CSF alone or with IL-2 enhances the immune response to sequentially administered vaccinia-CEA vaccine and ALVAC-CEA vaccine. IV. Compare the enzyme linked immunosorbent assay ELISPOT with lymphoproliferative and cytotoxicity assays for measuring CEA-specific T lymphocyte immune response.

PROTOCOL OUTLINE: This is two-stage, partially randomized study. In stage one, patients are randomized to arm I or II. Arm I: Patients receive vaccinia-carcinoembryonic antigen (CEA) vaccine intradermally on day 1 of course 1 and ALVAC-CEA vaccine (CEA-Avipox vaccine) intramuscularly (IM) on day 1 of courses 2-4. Each course lasts 28 days. Arm II: Patients receive ALVAC-CEA vaccine (CEA-Avipox vaccine) IM on day 1 of courses 1-3 and vaccinia-CEA vaccine intradermally on day 1 of course 4. Each course lasts 28 days. Patients in arms I and II continue 28-day courses through month 6 and then receive 3-month courses for 2 years in the absence of disease progression or unacceptable toxicity. In stage two, patients are enrolled successively into arms III and IV. Arm III: Patients receive vaccines according to whichever schedule (arm I or II) was found to be superior plus sargramostim (GM-CSF) subcutaneously (SC) on days 1-4 of each course. Each course lasts 28 days. Arm IV: Patients receive vaccines plus GM-CSF as in arm III and interleukin-2 SC once daily on days 7-11 of each course. Each course lasts 28 days. Patients on arms III and IV continue 28-day courses through month 6 and then receive 3-month courses for 2 years in the absence of disease progression or unacceptable toxicity. If 2 or more patients in either arm III or IV experience dose limiting toxicity, accrual into study stops. Otherwise, the best response among the 4 arms is determined and further HLA-A2 positive patients are enrolled into that arm so that a total of 6 HLA-A2 positive patients with advanced disease and 6 HLA-A2 positive patients with NED (without radiographic or clinical evidence of tumor) are treated. If more than one regimen is equally superior, the least toxic regimen is chosen for further accrual. Patients are followed at 28 days following the last vaccination.

PROJECTED ACCRUAL: A minimum of 24 patients (6 HLA-A2 positive and up to 3 HLA-A2 negative patients per arm) will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed malignancy that is stage IV and/or at high risk of recurrence despite standard treatment
• Stage IV malignancy that is surgically rendered free of macroscopic tumor allowed if current available treatment is not likely to offer a survival advantage or result in significant palliation
• If at high risk for recurrence, must have an estimated recurrence rate of at least 75% following definitive therapy, such as: Postresection of pancreatic cancer; Gastric cancer with regional lymph node involvement; Node positive stage II or stage III esophageal cancer; Stage IIIA or IIIB non-small cell lung cancer; Breast cancer with at least 10 positive axillary nodes
• Must have low tumor burden or no evidence of disease
• Must have evidence of prior vaccinia (for smallpox immunization)
• Must have CEA expressing type tumor or a serum CEA elevation of 10 or greater during course of disease
• No CNS metastases
• Hormone receptor status: Not specified

--Prior/Concurrent Therapy--

• Must have recovered from toxic effects of all prior therapy
• Biologic therapy: Prior vaccinia immunization required; No concurrent biologic therapy; No concurrent immunotherapy
• Chemotherapy: At least 4 weeks since prior chemotherapy (6 weeks since prior nitrosoureas or mitomycin); No concurrent chemotherapy
• Endocrine therapy: Physiologic replacement of steroids allowed; No concurrent hormonal therapy
• Radiotherapy: No prior radiotherapy to more than 50% of all nodal groups
• Surgery: At least 3 weeks since any prior major surgery

--Patient Characteristics--

• Age: 18 and over
• Menopausal status: Not specified
• Performance status: ECOG 0-1
• Life expectancy: At least 6 months
• Hematopoietic: Absolute granulocyte count at least 1,500/mm3; WBC at least 3,000/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 2.0 mg/dL OR Creatinine clearance at least 50 mL/min
• Other: HIV negative; No uncontrolled seizure disorders, encephalitis, or multiple sclerosis; No history of allergy or untoward reaction to prior vaccination with vaccinia virus; No other prior or concurrent diagnosis of altered immune function, including eczema, atopic dermatitis, or any autoimmune disease such as systemic lupus erythematosus, Sjogren's syndrome, scleroderma, myasthenia gravis, Goodpasture's syndrome, Addison's disease, Hashimoto's thyroiditis, or active Graves' disease; Must be maintaining a reasonable state of nutrition, consistent with weight maintenance; No frequent vomiting or severe anorexia; Must be able to avoid close contact with children 3 years or younger, pregnant women, individuals with eczema or history of eczema or other open skin conditions, or immunosuppressed individuals for at least 2 weeks after each vaccination; No serious concurrent medical illnesses including inflammatory bowel disease, Crohn's disease, ulcerative colitis, or active diverticulitis; Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception during and for at least 6 months after study

District of Columbia
      Lombardi Cancer Center, Georgetown University, Washington,  District of Columbia,  20007,  United States
Maryland
      National Naval Medical Center, Bethesda,  Maryland,  20889-5000,  United States

Study chairs or principal investigators

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

Study ID Numbers:  CDR0000065885; GUMC-97118; NCI-T97-0033
Record last reviewed:  April 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003125
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08