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

National Cancer Institute (NCI) logo

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)

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

Trial contacts and locations

0

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Data sourced from clinicaltrials.gov

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