Vaccine Therapy, Interleukin-2, and Sargramostim in Treating Patients With Advanced Tumors
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| ClinicalTrials.gov Identifier: NCT00003125 |
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Recruitment Status
:
Completed
First Posted
: April 14, 2004
Last Update Posted
: March 24, 2011
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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 |
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 |
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| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| 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
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 ClinicalTrials.gov 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 | |
| Study Chair: | John L. Marshall, MD | Lombardi Comprehensive Cancer Center |
| Responsible Party: | John Marshall, MD, Georgetown University |
| ClinicalTrials.gov Identifier: | NCT00003125 History of Changes |
| Other Study ID Numbers: |
CDR0000065885 U01CA062500 ( U.S. NIH Grant/Contract ) P30CA051008 ( U.S. NIH Grant/Contract ) GUMC-97118 NCI-T97-0033 |
| First Posted: | April 14, 2004 Key Record Dates |
| Last Update Posted: | March 24, 2011 |
| Last Verified: | May 2007 |
Keywords provided by Georgetown University:
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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:
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Breast Neoplasms Lung Neoplasms Pancreatic Neoplasms Stomach Neoplasms Esophageal Neoplasms Neoplasms by Site Neoplasms 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 Vaccines Aldesleukin Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents Anti-HIV Agents Anti-Retroviral Agents |