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 Advanced or Metastatic Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Completed 18 and over NCI FCCC-01016 NCI-1133, NCT00028496, 1133

Objectives

1. 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.
2. Determine the CEA-specific T-cell precursor frequency in patients treated with these regimens.
3. Assess the immunogenicity of GM-CSF in patients treated with these regimens.
4. Determine the inflammatory response and cytokine expression at the vaccination site in these patients 48 hours after vaccination.
5. Correlate telomere length of leukocytes with prior cytotoxic therapies and immunologic response in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed adenocarcinoma that failed standard curative options and for which no standard palliative options are required within the next 8 weeks
  • Advanced or metastatic disease
  • Recurrent or unresectable disease
  • Microscopic metastatic disease confirmed by surgical exploration allowed



• CEA expression by immunohistochemistry

  OR




• 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

Prior/Concurrent Therapy:

Biologic therapy:

• 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

Chemotherapy:

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No concurrent antineoplastic chemotherapy

Endocrine therapy:

• 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

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered
• No prior radiotherapy to more than 50% of all nodal groups

Surgery:

• See Disease Characteristics
• Recovered from prior surgery
• No prior splenectomy

Other:

• Concurrent non-steroidal anti-inflammatory drugs allowed
• No other concurrent anti-cancer therapy

Patient Characteristics:

Age:

• 18 and over

Sex:

• Male or female

Menopausal status:

• Not specified

Performance status:

• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• WBC at least 3,000/mm³
• Platelet count at least 100,000/mm³

Hepatic:

• 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)

Renal:

• Creatinine less than 1.5 mg/dL

  OR

• Creatinine clearance greater than 60 mL/min
• Proteinuria or hematuria less than +2 on urinalysis*

  OR

• Urine protein less than 1,000 mg/24-hour collection, if proteinuria greater than +1

 [Note: Proteinuria of +2 allowed provided etiology is non-renal]

Gastrointestinal:

• 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

Neurologic:

• No uncontrolled seizure disorders
• No encephalitis
• No multiple sclerosis

Immunologic:

• 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

Other:

• 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

Expected Enrollment

A total of 48 patients will be accrued for this study within 1.2 years.

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.

Trial Contact Information

Trial Lead Organizations

Fox Chase Cancer Center - Philadelphia

Margaret von Mehren, MD, Protocol chair		Ph: 215-728-3545; 888-369-2427

Registry Information
Official Title		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
Trial Start Date		2002-01-28
Registered in ClinicalTrials.gov		NCT00028496
Date Submitted to PDQ		2001-10-24
Information Last Verified		2003-08-29
NCI Grant/Contract Number		CA06927