Vaccine Therapy, Interleukin-2, and Sargramostim in Treating Patients With Advanced Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00003125
Recruitment Status : Completed
First Posted : April 14, 2004
Last Update Posted : March 24, 2011
National Cancer Institute (NCI)
Information provided by:
Georgetown University

Brief Summary:

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 or disease Intervention/treatment Phase
Breast Cancer Esophageal Cancer Gastric Cancer Lung Cancer Pancreatic Cancer Unspecified Adult Solid Tumor, Protocol Specific Biological: ALVAC-CEA vaccine Biological: aldesleukin Biological: sargramostim Biological: vaccinia-CEA vaccine Phase 2

Detailed Description:

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.

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Primary Purpose: Treatment
Official Title: A Pilot Study of Sequential Vaccinations With ALVAC-CEA and Vaccinia-CEA With the Addition of IL-2 and GM-CSF in Patients With CEA Expressing Tumors
Study Start Date : January 1998
Actual Primary Completion Date : November 2004
Actual Study Completion Date : November 2004

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00003125

United States, District of Columbia
Lombardi Cancer Center, Georgetown University
Washington, District of Columbia, United States, 20007
United States, Maryland
National Naval Medical Center
Bethesda, Maryland, United States, 20889-5000
Sponsors and Collaborators
Georgetown University
National Cancer Institute (NCI)
Study Chair: John L. Marshall, MD Lombardi Comprehensive Cancer Center

Responsible Party: John Marshall, MD, Georgetown University Identifier: NCT00003125     History of Changes
Other Study ID Numbers: CDR0000065885
U01CA062500 ( U.S. NIH Grant/Contract )
P30CA051008 ( U.S. NIH Grant/Contract )
First Posted: April 14, 2004    Key Record Dates
Last Update Posted: March 24, 2011
Last Verified: May 2007

Keywords provided by Georgetown University:
stage IV breast cancer
stage IIIA breast cancer
stage III gastric cancer
stage IV gastric cancer
stage IIIB breast cancer
stage II pancreatic cancer
stage III pancreatic cancer
stage II esophageal cancer
stage III esophageal cancer
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
unspecified adult solid tumor, protocol specific
stage IV pancreatic cancer

Additional relevant MeSH terms:
Breast Neoplasms
Lung Neoplasms
Pancreatic Neoplasms
Stomach Neoplasms
Esophageal Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gastrointestinal Neoplasms
Gastrointestinal Diseases
Stomach Diseases
Head and Neck Neoplasms
Esophageal Diseases
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Anti-HIV Agents
Anti-Retroviral Agents