Clinical trial NCT00217373: Vaccine Therapy, GM-CSF, and Interferon Alfa-2b in Treating Patients With Locally Advanced or Metastatic Cancer That Expresses Carcinoembryonic Antigen (CEA)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Adult Solid Neoplasm
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2005-09-22
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
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
timeFrame: Up to 112 days
Secondary outcomes:
measure: Incidence of adverse events, graded according to NCI CTCAE version 4.0
timeFrame: Up to 15 years
measure: Response to treatment, evaluated using the new international criteria proposed by the RECIST Committee
timeFrame: Up to 15 years
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center
name: William Carson
role: PRINCIPAL_INVESTIGATOR
References: