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Vaccine Therapy, GM-CSF, and Interferon Alfa-2b in Treating Patients With Locally Advanced or Metastatic Cancer That Expresses Carcinoembryonic Antigen (CEA)

Information source: National Cancer Institute (NCI)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Adult Solid Neoplasm

Intervention: Recombinant Fowlpox-CEA(6D)/TRICOM Vaccine (Biological); Recombinant Interferon Alfa-2b (Biological); Recombinant Vaccinia-CEA(6D)-TRICOM Vaccine (Biological); Sargramostim (Biological)

Phase: Phase 1

Status: Completed

Sponsored by: National Cancer Institute (NCI)

Official(s) and/or principal investigator(s):
William Carson, Principal Investigator, Affiliation: Ohio State University Comprehensive Cancer Center


This phase I trial is studying the side effects and best dose of interferon alfa-2b when given together with vaccine therapy and GM-CSF in treating patients with locally advanced or metastatic cancer that makes CEA. Vaccines made from a gene-modified virus may help the body build an effective immune response to kill cancer cells that make carcinoembryonic antigen (CEA). Biological therapies, such as GM-CSF, may stimulate the immune system in different ways and stop cancer cells from growing. Interferon alfa-2b may interfere with the growth of cancer cells and slow cancer growth. Giving vaccine therapy together with GM-CSF and interferon alfa-2b may kill more cancer cells that make CEA.

Clinical Details

Official title: 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

Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 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

Secondary outcome:

Incidence of adverse events, graded according to NCI CTCAE version 4.0

Response to treatment, evaluated using the new international criteria proposed by the RECIST Committee

Detailed description: 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.


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


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


- 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

Locations and Contacts

Ohio State University Comprehensive Cancer Center, Columbus, Ohio 43210, United States
Additional Information

Starting date: June 2005
Last updated: April 17, 2015

Page last updated: August 23, 2015

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