A Phase I Study of Sequential Vaccinations With Fowlpox-CEA(6D)-Tricom (B7.1/ICAM/LFA3) and Vaccinia-CEA (6D)-Tricom, in Combination With GM-CSF and Interferon-Alfa-2B in Patients With CEA-Expressing Carcinomas
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I Study of Sequential Vaccinations With Fowlpox-CEA(6D)-Tricom (B7.1/ICAM/LFA3) and Vaccinia-CEA (6D)-Tricom, in Combination With GM-CSF and Interferon-Alfa-2B in Patients With CEA-Expressing Carcinomas
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose and recommended phase II dose of interferon alfa-2b
(IFN-α-2b) when administered with recombinant vaccinia-CEA(6D)-TRICOM vaccine, recombinant
fowlpox-CEA(6D)-TRICOM vaccine, and sargramostim (GM-CSF) in patients with locally advanced
or metastatic carcinoembryonic antigen (CEA)-expressing carcinoma.
SECONDARY OBJECTIVES:
I. Determine the effect of IFN-α-2b on tumor cell expression of CEA and MHC class I antigens
in patients treated with this regimen.
II. Determine the immunologic effects of this regimen in these patients. III. Determine any
objective anti-tumor responses that may occur in response to this regimen in these patients.
IV. Determine the time to tumor progression in patients treated with this regimen.
OUTLINE: This is a dose-escalation study of interferon alfa-2b (IFN-α-2b).
COURSE I: Patients receive recombinant vaccinia-CEA(6D)-TRICOM vaccine subcutaneously (SC)
on day 1. Patients also receive sargramostim (GM-CSF) SC on days 1-4 and IFN-α-2b* SC on
days 9, 11, and 13.
COURSES II-IV: Patients receive recombinant fowlpox-CEA(6D)-TRICOM vaccine SC on day 1.
Patients also receive GM-CSF as in course 1 and IFN-α-2b* SC on days 1, 3, and 5.
NOTE: *The initial cohort of 6 patients does not receive IFN-α-2b.
Treatment repeats every 28 days for 4 courses in the absence of disease progression or
unacceptable toxicity. After 4 courses, patients who do not have progressive disease or
unacceptable toxicity may receive recombinant fowlpox-CEA (6D)-TRICOM vaccine, GM-CSF, and
IFN-α-2b every 28 days for 2 more courses and then every 3 months for up to 2 years.
Cohorts of 3-6 patients receive escalating doses of IFN-α-2b until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity. Six additional patients are treated at the
MTD; these patients must be HLA-A2 positive.
After completion of study treatment, patients are followed monthly for 4 months and then
every 6-12 months for up to 15 years.
Inclusion Criteria:
- Histologically confirmed carcinoembryonic antigen (CEA)-expressing carcinoma
- Metastatic or locally advanced disease
- Tumor accessible for biopsy
- Must have received ≥ 1 prior systemic regimen for metastatic disease
- No known brain metastases
- Performance status - ECOG 0-2
- Performance status - Karnofsky 60-100%
- More than 6 months
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Bilirubin ≤ 2.0 times upper limit of normal (ULN)
- AST and ALT ≤ 4.0 times ULN
- Hepatitis B negative
- Hepatitis C negative
- Creatinine ≤ 1.96 mg/dL
- Creatinine clearance > 50 mL/min
- No persistent proteinuria
- Protein < 1,000 mg by 24-hour urine collection
- No urinary sediment abnormalities
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- No clinically significant cardiomyopathy requiring treatment
- No impaired function (i.e., ejection fraction < 50%) for patients who have not had
prior vaccine and are asymptomatic
- HIV negative
- No ongoing or active infection
- No history of allergic reaction to eggs or egg products
- No history of allergy or untoward reaction to prior vaccinia vaccination (e.g.,
smallpox immunization) or to any of its components
- No history of or active eczema or other eczematoid skin disorders
- No atopic dermatitis
- No other acute, chronic, or exfoliative skin conditions, including any of the
following:
- Burns
- Impetigo
- Varicella zoster
- Severe acne
- Other open wounds or rashes
- No immunocompromised condition
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for ≥ 3 months after
completion of study treatment
- No sexual contact for 3 weeks after each vaccination treatment
- Must be willing to undergo tumor biopsy
- No psychiatric illness or social situation that would preclude study compliance
- No life-threatening illness
- No other active malignancy within the past 2 years except nonmelanoma skin cancer or
superficial bladder or cervical lesions treated with surgical resection
- No other uncontrolled illness
- Must be able to avoid close household contact with the following individuals for ≥ 3
weeks after vaccinia vaccination:
- Pregnant or nursing women
- Children under 5 years of age
- Individuals who are immunodeficient or immunosuppressed by disease or therapy
(including HIV infection)
- Individuals with the following conditions:
- History of or active eczema or other eczematoid skin disorders
- Atopic dermatitis
- Other acute, chronic, or exfoliative skin conditions (e.g., burns,
impetigo, varicella zoster, severe acne, or other open rashes or wounds)
- No concurrent influenza vaccine
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
and recovered
- No concurrent steroid therapy, except topical or inhaled steroids
- No concurrent steroid eye drops
- More than 4 weeks since prior radiotherapy and recovered
- More than 4 weeks since prior surgery and recovered
- No prior splenectomy
- No other concurrent investigational agents
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
MTD of IFN-alpha-2b, defined as the dose level one level beneath that dose at which 2 or more of 6 patients showed DLT, graded according to NCI CTCAE version 4.0
Outcome Time Frame:
Up to 112 days
Safety Issue:
Yes
Principal Investigator
William Carson
Investigator Role:
Principal Investigator
Investigator Affiliation:
Ohio State University
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2011-01347
NCT ID:
NCT00217373
Start Date:
June 2005
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
Name | Location |
|---|---|
| Ohio State University Medical Center | Columbus, Ohio 43210 |
