Clinical trial NCT00028496: Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Adenocarcinoma of the Colon
Adenocarcinoma of the Gallbladder
Adenocarcinoma of the Pancreas
Adenocarcinoma of the Rectum
Adult Primary Hepatocellular Carcinoma
Advanced Adult Primary Liver Cancer
Cholangiocarcinoma of the Gallbladder
Diffuse Adenocarcinoma of the Stomach
Intestinal Adenocarcinoma of the Stomach
Male Breast Cancer
Mixed Adenocarcinoma of the Stomach
Ovarian Endometrioid Adenocarcinoma
Paget Disease of the Breast With Intraductal Carcinoma
Paget Disease of the Breast With Invasive Ductal Carcinoma
Recurrent Adult Primary Liver Cancer
Recurrent Breast Cancer
Recurrent Colon Cancer
Recurrent Gallbladder Cancer
Recurrent Gastric Cancer
Recurrent Malignant Testicular Germ Cell Tumor
Recurrent Pancreatic Cancer
Recurrent Rectal Cancer
Recurrent Salivary Gland Cancer
Salivary Gland Adenocarcinoma
Stage II Malignant Testicular Germ Cell Tumor
Stage II Pancreatic Cancer
Stage III Colon Cancer
Stage III Gastric Cancer
Stage III Malignant Testicular Germ Cell Tumor
Stage III Pancreatic Cancer
Stage III Rectal Cancer
Stage III Salivary Gland Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IV Breast Cancer
Stage IV Colon Cancer
Stage IV Gastric Cancer
Stage IV Pancreatic Cancer
Stage IV Rectal Cancer
Stage IV Salivary Gland Cancer
Thyroid Gland Medullary Carcinoma
Unresectable Gallbladder Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 48
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: 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

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.

Eligibility 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

Primary outcomes:
measure: 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
timeFrame: 56 days
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
Study officials:
affiliation: Fox Chase Cancer Center
name: Margaret von Mehren
role: PRINCIPAL_INVESTIGATOR
References: