NCT00128622CompletedPhase 1
A Phase I Study of Regulatory T Cell Depletion With Denileukin Diftitox Followed by Active Immunotherapy With Autologous Dendritic Cells Infected With CEA-6D Expressing Fowlpox-Tricom in Patients With Advanced or Metastatic Malignancies Expressing CEA
H. Kim Lyerly2 sites in 1 country24 target enrollmentStarted: September 1, 2005Last updated:
Conditions
Interventions
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 24
- Locations
- 2
- Primary Endpoint
- Safety as measured by rate of adverse events during study drug treatment
Study Overview
Brief Summary
RATIONALE: Combinations of biological substances in denileukin diftitox may be able to carry cancer-killing substances directly to the cancer cells. Vaccines made from a gene-modified virus and a person's white blood cells may help the body build an effective immune response to kill cancer cells. Giving denileukin diftitox together with vaccine therapy may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects of giving denileukin diftitox together with vaccine therapy in treating patients with metastatic cancer that expresses carcinoembryonic antigen.
Detailed Description
OBJECTIVES:
Primary
- Determine the safety and feasibility of two different schedules of denileukin diftitox followed by active immunotherapy comprising autologous dendritic cells infected with recombinant fowlpox-CEA(6D)-TRICOM vaccine in patients with metastatic CEA-expressing malignancies.
Secondary
- Determine the immune response to this regimen in these patients.
- Determine, preliminarily, clinical response rate and/or time to progression in patients with assessable disease treated with this regimen.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed malignancy
- •Metastatic disease
- •Tumor expresses carcinoembryonic antigen (CEA), as evidenced by any of the following:
- •At least 50% of tumor expresses CEA by immunohistochemistry (IHC) with ≥ a moderate intensity of staining
- •Peripheral blood CEA level > 5.0 ng/mL
- •Tumor known to be universally CEA-positive (e.g., colon or rectal cancer)
- •Measurable or evaluable disease
- •Received or refused prior therapy with a possible survival or palliative benefit AND meets the following disease-specific criteria:
- •Patients with colorectal cancer must have experienced disease progression during ≥ 1 prior palliative chemotherapy regimen for metastatic disease comprising 1 of the following regimens:
- •Fluorouracil or capecitabine AND oxaliplatin
- •Fluorouracil or capecitabine AND irinotecan
- •Chemotherapy in combination with bevacizumab
- •Patients with breast cancer must have experienced disease progression during ≥ 1 prior palliative chemotherapy regimen for metastatic disease comprising 1 of the following regimens:
- •Anthracycline- or taxane-based chemotherapy
- •Chemotherapy AND trastuzumab (Herceptin®) (required for patients with tumors overexpressing HER2/neu (i.e., 3+ by IHC or positive by fluorescence in situ hybridization [FISH])
- •Patients with lung cancer must have experienced disease progression during ≥ 1 prior palliative chemotherapy regimen for metastatic disease comprising 1 of the following regimens:
- •Platinum-based (e.g., cisplatin or carboplatin) chemotherapy (for chemotherapy-naive patients only)
- •Taxane-based (e.g., docetaxel or paclitaxel) chemotherapy OR vinorelbine (for patients who received prior chemotherapy)
- •Patients with pancreatic cancer must have experienced disease progression during prior chemotherapy, including gemcitabine
- •Patients with other malignancies must have experienced disease progression after prior first-line therapy that would confer a survival or palliative benefit, if such a therapy exists
- •Patients who experienced disease progression during prior first-line palliative chemotherapy must be advised regarding second-line therapy before study enrollment
- •Previously resected brain metastases allowed provided there is no evidence of brain metastasis within the past month by MRI or CT scan
- •No requirement for further systemic chemotherapy for ≥ 3 months
- •Hormone receptor status:
- •Not specified
- •PATIENT CHARACTERISTICS:
- •18 and over
- •Male or female
- •Menopausal status
- •Not specified
- •Performance status
- •Karnofsky 70-100%
- •Life expectancy
- •More than 6 months
- •Hematopoietic
- •WBC ≥ 3,000/mm^3
- •Hemoglobin ≥ 9 g/dL (transfusion or epoetin alfa allowed)
- •Platelet count ≥ 100,000/mm^3
- •Bilirubin < 1.5 mg/dL (≤ 2.0 mg/dL for patients with Gilbert's syndrome)
- •SGOT and SGPT < 1.5 times upper limit of normal
- •Albumin ≥ 3.0 g/dL
- •No active acute or chronic viral hepatitis
- •Hepatitis B surface antigen negative
- •Hepatitis C negative
- •No other hepatic disease that would preclude study treatment
- •Creatinine < 1.5 mg/dL
- •No active acute or chronic urinary tract infection
- •Cardiovascular
- •No New York Heart Association class III-IV cardiac disease
- +40 more not shown
Exclusion Criteria
- Not provided
Arms & Interventions
Denileukin Diftitox plus vaccine
Experimental
This is a single arm Phase I safety study.
Intervention: recombinant fowlpox-CEA(6D)/TRICOM vaccine (Biological)
Denileukin Diftitox plus vaccine
Experimental
This is a single arm Phase I safety study.
Intervention: therapeutic autologous dendritic cells (Biological)
Denileukin Diftitox plus vaccine
Experimental
This is a single arm Phase I safety study.
Intervention: denileukin diftitox (Biological)
Outcomes
Primary Outcomes
Safety as measured by rate of adverse events during study drug treatment
Time Frame: 3 months
Secondary Outcomes
- Rate of immune response as measured by ELISPot at week 10(3 months)
Investigators
H. Kim Lyerly
Professor, Gen & Thor Surgery
Duke University
Study Sites (2)
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