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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

Phase 2
18 Years
Not Enrolling
Breast Cancer, Esophageal Cancer, Gastric Cancer, Lung Cancer, Pancreatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

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

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.

Inclusion 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

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

Type of Study:


Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Principal Investigator

John L. Marshall, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Lombardi Cancer Research Center


United States: Federal Government

Study ID:




Start Date:

January 1998

Completion Date:

November 2004

Related Keywords:

  • Breast Cancer
  • Esophageal Cancer
  • Gastric Cancer
  • Lung Cancer
  • Pancreatic Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • 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
  • Breast Neoplasms
  • Esophageal Diseases
  • Esophageal Neoplasms
  • Lung Neoplasms
  • Stomach Neoplasms
  • Pancreatic Neoplasms



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