Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer

January 24, 2013 updated by: National Cancer Institute (NCI)

Phase I Study of a Recombinant Fowl Pox Vaccine rF-CEA (6D)/TRICOM Alone or With GM-CSF in Patients With Advanced CEA Expressing Adenocarinomas

Phase I trial to study the effectiveness of vaccine therapy with or without sargramostim in treating patients who have advanced or metastatic cancer. Vaccines may make the body build an immune response to kill tumor cells. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood. Combining vaccine therapy with sargramostim may make tumor cells more sensitive to the vaccine and may kill more tumor cells

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the toxicity of recombinant fowlpox-CEA-TRICOM vaccine with or without sargramostim (GM-CSF) or recombinant fowlpox-GM-CSF in patients with advanced or metastatic CEA-expressing adenocarcinomas.

II. Determine the CEA-specific T-cell precursor frequency in patients treated with these regimens.

III. Assess the immunogenicity of GM-CSF in patients treated with these regimens.

IV. Determine the inflammatory response and cytokine expression at the vaccination site in these patients 48 hours after vaccination.

V. Correlate telomere length of leukocytes with prior cytotoxic therapies and immunologic response in patients treated with these regimens.

OUTLINE: This is a dose-escalation study. The first three cohorts of 3-12 patients receive escalating doses of recombinant fowlpox-CEA-TRICOM vaccine (fCEA-TRI) until the maximum tolerated dose (MTD) is determined.

The MTD is defined as the dose preceding that at which 2 of 6 patients or 3 of 12 patients experience dose-limiting toxicity. fCEA-TRI is administered intradermally every 2 weeks for 4 doses and then every 2 months thereafter (beginning on day 56) in the absence of disease progression or unacceptable toxicity.

The fourth and fifth cohorts of 6 patients receive fCEA-TRI at the MTD in the same manner as the first three cohorts combined with escalating doses of sargramostim (GM-CSF). GM-CSF is administered subcutaneously once daily beginning on the day of each vaccination and continuing for a total of 4 days.

The sixth through eighth cohorts of 6 patients receive fCEA-TRI at the MTD in the same manner as the first three cohorts combined with escalating doses of recombinant fowlpox-GM-CSF (rF-GM-CSF). rF-GM-CSF is administered in the same manner as GM-CSF.

Patients are followed every month for 4 months.

Study Type

Interventional

Enrollment (Actual)

48

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111-2497
        • Fox Chase Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma that failed standard curative options and for which no standard palliative options are required within the next 8weeks

    • Advanced or metastatic disease
    • Recurrent or unresectable disease
    • Microscopic metastatic disease confirmed by surgical exploration allowed
  • CEA expression by immunohistochemistry
  • Circulating CEA greater than 5 ng/mL

  • HLA phenotyping required

    • HLA phenotyping must be repeated for patients who have undergone allogeneic bone marrow transplantation

  • No clinically symptomatic brain metastases

    • Patients with brain metastases who have completed palliative radiotherapy and have discontinued steroids are eligible

  • Hormone receptor status:

    • Not specified
  • Male or female
  • Performance status - ECOG 0-1
  • WBC at least 3,000/mm^3
  • Platelet count at least 100,000/mm^3
  • Bilirubin less than 1.5 times upper limit of normal (ULN)
  • AST and ALT less than 3 times ULN
  • PT and PTT less than 1.5 times ULN (unless therapeutically anticoagulated)
  • Creatinine less than 1.5 mg/dL
  • Creatinine clearance greater than 60 mL/min
  • Proteinuria or hematuria less than +2 on urinalysis*
  • Urine protein less than 1,000 mg/24-hour collection, if proteinuria greater than +1
  • No frequent vomiting or severe anorexia
  • No more than 10% weight loss within the past 3 months
  • No inflammatory bowel disease, Crohn's disease, ulcerative colitis, or active diverticulitis
  • No uncontrolled seizure disorders
  • No encephalitis
  • No multiple sclerosis
  • No allergy to eggs
  • No HIV-associated opportunistic infection

  • No autoimmune diseases, including the following:

    • Systemic lupus erythematosus
    • Sjögren's syndrome
    • Scleroderma
    • Myasthenia gravis
    • Goodpasture syndrome
    • Addison's disease
    • Hashimoto's thyroiditis
    • Graves' disease
  • Antinuclear antibody positive status allowed if no evidence of an autoimmune disease

  • No direct contact of vaccination site with the following persons for at least 72 hours after each vaccination:

    • Children under 1 year of age
    • Pregnant women
    • Individuals with eczema or other open skin condition
    • Immunocompromised individuals
  • No other concurrent serious medical illness that would preclude study entry
  • No other malignancy within the past 2 years except excised basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception for at least 1 month before (female patients only), during, and for at least 3 months after study participation
  • See Disease Characteristics
  • No prior CEA-directed active immunotherapy
  • Prior CEA-directed antibody therapy allowed
  • At least 4 weeks since prior immunotherapy and recovered
  • No other concurrent antineoplastic biologic therapy or immunotherapy
  • At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
  • No concurrent antineoplastic chemotherapy
  • See Disease Characteristics
  • No concurrent antineoplastic hormonal therapy
  • No concurrent systemic steroids (inhaled steroids allowed)
  • Concurrent systemic mineralocorticoids (e.g., megestrol for appetite stimulation or fludrocortisone) allowed
  • Concurrent birth control pills allowed
  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy and recovered
  • No prior radiotherapy to more than 50% of all nodal groups
  • See Disease Characteristics
  • Recovered from prior surgery
  • No prior splenectomy
  • Concurrent non-steroidal anti-inflammatory drugs allowed
  • No other concurrent anti-cancer therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (vaccine therapy, sargramostim, vaccine adjuvant)

The first three cohorts of 3-12 patients receive escalating doses of recombinant fowlpox-CEA-TRICOM vaccine (fCEA-TRI) until the maximum tolerated dose (MTD) is determined. fCEA-TRI is administered intradermally every 2 weeks for 4 doses and then every 2 months thereafter (beginning on day 56) in the absence of disease progression or unacceptable toxicity.

The fourth and fifth cohorts of 6 patients receive fCEA-TRI at the MTD in the same manner as the first three cohorts combined with escalating doses of sargramostim (GM-CSF). GM-CSF is administered subcutaneously once daily beginning on the day of each vaccination and continuing for a total of 4 days.

The sixth through eighth cohorts of 6 patients receive fCEA-TRI at the MTD in the same manner as the first three cohorts combined with escalating doses of recombinant fowlpox-GM-CSF (rF-GM-CSF).
Biological: sargramostim
Given subcutaneously
Other Names:
  • Leukine
  • Prokine
  • GM-CSF
Biological: recombinant fowlpox-CEA(6D)/TRICOM vaccine
Given intradermally
Other Names:
  • fowlpox-CEA-B7-1/ICAM-1/LFA-3
  • rF-CEA(6D)TRICOM
Biological: recombinant fowlpox GM-CSF vaccine adjuvant
Given intradermally
Other Names:
  • fowlpox-GM-CSF
  • fowlpox-sargramostim
  • rf-GM-CSF
  • rf-sargramostim

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum tolerated dose of recombinant fowlpox-CEA(6D)/TRICOM vaccine determined by dose-limiting toxicities graded according to NCI Common Toxicity Criteria, version 2.0
Time Frame: 56 days
56 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2001

Primary Completion (Actual)

November 1, 2005

Study Registration Dates

First Submitted

January 4, 2002

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

January 25, 2013

Last Update Submitted That Met QC Criteria

January 24, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02433
  • FCCC-01016
  • CDR0000069093 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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