Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Vaccine Therapy With or Without Sargramostim in Treating Patients With Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 and over NCI GUMC-00101 GUMC-IBC20-09, NIH/OBA-0006-405, NCI-833, NCT00009958, 833

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.

Entry Criteria

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

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 

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

Expected Enrollment

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

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.
 

Trial Contact Information

Trial Lead Organizations

Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

John Marshall, MD, Protocol chair		Ph: 202-444-7064

Registry Information
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
Trial Start Date		2000-11-22
Registered in ClinicalTrials.gov		NCT00009958
Date Submitted to PDQ		2000-12-13
Information Last Verified		2002-07-01
NCI Grant/Contract Number		P30-CA51008