Vaccine Therapy With Or Without Sargramostim In Treating Patients With Advanced Or Metastatic Cancer

Study Overview

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

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

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.

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

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

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

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2002-01-04	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2013-01-24
First Submitted that Met QC Criteria 2003-01-26	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2013-01-25
First Posted (ESTIMATED) 2003-01-27	Results First Posted N/A	Last Verified 2013-01

Study Plan

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

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

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	BIOLOGICAL: recombinant fowlpox-CEA(6D)/TRICOM vaccine Given intradermally BIOLOGICAL: sargramostim Given subcutaneously BIOLOGICAL: recombinant fowlpox GM-CSF vaccine adjuvant Given intradermally

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

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

Given intradermally

BIOLOGICAL: sargramostim

Given subcutaneously

BIOLOGICAL: recombinant fowlpox GM-CSF vaccine adjuvant

Given intradermally

Primary Outcome Measures	Measure Description	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		56 days

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

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

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

Collaborators and Investigators

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

Investigators

PRINCIPAL_INVESTIGATOR: Margaret von Mehren, Fox Chase Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Clinical Trial Record