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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

Conditions: Stage IIIA Breast Cancer; Stage IV Salivary Gland Cancer; Stage III Rectal Cancer; Recurrent Gallbladder Cancer; Stage IV Gastric Cancer; Adenocarcinoma of the Colon; Diffuse Adenocarcinoma of the Stomach; Male Breast Cancer; Advanced Adult Primary Liver Cancer; Stage IIIB Breast Cancer; Adenocarcinoma of the Gallbladder; Recurrent Gastric Cancer; Adenocarcinoma of the Rectum; Stage III Colon Cancer; Salivary Gland Adenocarcinoma; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Paget Disease of the Breast With Intraductal Carcinoma; Recurrent Adult Primary Liver Cancer; Stage III Malignant Testicular Germ Cell Tumor; Recurrent Colon Cancer; Paget Disease of the Breast With Invasive Ductal Carcinoma; Stage IV Pancreatic Cancer; Recurrent Malignant Testicular Germ Cell Tumor; Adenocarcinoma of the Pancreas; Unresectable Gallbladder Cancer; Cholangiocarcinoma of the Gallbladder; Intestinal Adenocarcinoma of the Stomach; Thyroid Gland Medullary Carcinoma; Adult Primary Hepatocellular Carcinoma; Stage II Malignant Testicular Germ Cell Tumor; Stage IV Rectal Cancer; Stage IV Colon Cancer; Stage III Salivary Gland Cancer; Stage II Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Breast Cancer; Recurrent Salivary Gland Cancer; Stage IV Breast Cancer; Stage III Gastric Cancer; Ovarian Endometrioid Adenocarcinoma; Mixed Adenocarcinoma of the Stomach

Treatments: Biological: sargramostim; Biological: recombinant fowlpox GM-CSF vaccine adjuvant; Biological: recombinant fowlpox-CEA(6D)/TRICOM vaccine

Study type: Interventional

Funder types: NIH

Identifiers

NCT00028496

NCI-2012-02433

CDR0000069093 (Registry Identifier)

FCCC-01016

Details and patient eligibility

About

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

Full 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.

Enrollment: 48 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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48 participants in 1 patient group

Treatment (vaccine therapy, sargramostim, vaccine adjuvant)

Experimental group

Description:

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).

Treatment:

Biological: recombinant fowlpox-CEA(6D)/TRICOM vaccine

Biological: recombinant fowlpox GM-CSF vaccine adjuvant

Biological: sargramostim