Denileukin Diftitox Followed by Vaccine Therapy in Treating Patients With Metastatic Cancer
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ClinicalTrials.gov Identifier: NCT00128622 |
Recruitment Status
:
Completed
First Posted
: August 10, 2005
Last Update Posted
: November 12, 2012
|
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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.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Breast Cancer Colorectal Cancer Lung Cancer Pancreatic Cancer Unspecified Adult Solid Tumor, Protocol Specific | Biological: denileukin diftitox Biological: recombinant fowlpox-CEA(6D)/TRICOM vaccine Biological: therapeutic autologous dendritic cells | Phase 1 |
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.
OUTLINE: Patients undergo leukapheresis for collection of peripheral blood mononuclear cells (PBMCs). PBMCs are cultured with sargramostim (GM-CSF) and interleukin-4 for the production of dendritic cells( DC). DC are mixed with recombinant fowlpox-TRICOM to produce the vaccine. Patients are assigned to 1 of 2 cohorts according to timing of study enrollment.
- Cohort 1: Patients receive denileukin diftitox IV over at least 15 minutes once in week 0 and vaccine therapy comprising autologous DC infected with recombinant fowlpox-CEA (6D)-TRICOM vaccine intradermally and subcutaneously once in weeks 0 (beginning 4 days after the denileukin diftitox infusion), 3, 6, and 9. If < 2 of 6 patients experience dose-limiting toxicity, a second cohort of patients is enrolled.
- Cohort 2: Patients receive denileukin diftitox as in cohort 1 once in weeks 0, 3, 6, and 9 and vaccine as in cohort 1.
In both cohorts, treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed annually for up to 15 years.
PROJECTED ACCRUAL: A total of 6-12 patients (6 per cohort) will be accrued for this study.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 24 participants |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | 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 |
Study Start Date : | September 2005 |
Actual Primary Completion Date : | March 2007 |
Actual Study Completion Date : | May 2009 |
Arm | Intervention/treatment |
---|---|
Experimental: Denileukin Diftitox plus vaccine
This is a single arm Phase I safety study.
|
Biological: denileukin diftitox Biological: recombinant fowlpox-CEA(6D)/TRICOM vaccine Biological: therapeutic autologous dendritic cells |
- Safety as measured by rate of adverse events during study drug treatment [ Time Frame: 3 months ]
- Rate of immune response as measured by ELISPot at week 10 [ Time Frame: 3 months ]

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Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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
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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
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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
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- 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:
Age
- 18 and over
Sex
- 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
Hepatic
- 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
Renal
- Creatinine < 1.5 mg/dL
- No active acute or chronic urinary tract infection
Cardiovascular
- No New York Heart Association class III-IV cardiac disease
Immunologic
- HIV negative
-
No history of autoimmune disease*, including, but not limited to, the following:
- Inflammatory bowel disease
- Systemic lupus erythematosus
- Ankylosing spondylitis
- Scleroderma
- Multiple sclerosis
-
No active cytomegalovirus (CMV) disease
- Patients with CMV-seropositivity are eligible
- No other active acute or chronic infection
- No history of allergies to eggs or any component of the study vaccine, denileukin diftitox, or diphtheria toxin NOTE: *Patients with a positive anti-nuclear antibody (ANA) ≤ 1:256 with no other evidence of autoimmune disease are eligible
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 4 months after completion of study treatment
- No acute or chronic skin disorder that would preclude study treatment
- No other malignancy within the past 5 years except nonmelanoma skin cancer, controlled carcinoma in situ of the cervix, or controlled superficial bladder cancer
- No psychological or medical impediment that would preclude study compliance
- No other serious acute or chronic illness that would preclude study treatment
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- Prior vaccine, dendritic cell, or CEA-targeted immunotherapy allowed
- At least 4 weeks since prior and no other concurrent immunotherapy
- Concurrent palliative single-agent trastuzumab for breast cancer allowed provided patient has been on therapy for ≥ 3 months before study entry
Chemotherapy
- See Disease Characteristics
- At least 4 weeks since prior and no concurrent chemotherapy
Endocrine therapy
- At least 4 weeks since prior hormonal therapy
- At least 6 weeks since prior steroid therapy except steroids used as premedication for chemotherapy or contrast-enhanced studies
- No concurrent steroids, including corticosteroids administered to manage toxic effects from dendritic cell or denileukin diftitox administration
- Concurrent palliative endocrine therapy for breast cancer allowed provided patient has been on therapy for ≥ 3 months before study entry
Radiotherapy
- At least 4 weeks since prior and no concurrent radiotherapy
Surgery
- See Disease Characteristics
Other
- Recovered from all prior therapy
- At least 4 weeks since prior investigational drugs or procedures
- At least 4 weeks since other prior therapy
- No other concurrent immunosuppressive therapy (e.g., azathioprine or cyclosporine)

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00128622
United States, District of Columbia | |
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center | |
Washington, District of Columbia, United States, 20007 | |
United States, North Carolina | |
Duke Comprehensive Cancer Center | |
Durham, North Carolina, United States, 27710 |
Study Chair: | Michael A. Morse, MD | Duke Cancer Institute |
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | H. Kim Lyerly, Professor, Gen & Thor Surgery, Duke University Medical Center |
ClinicalTrials.gov Identifier: | NCT00128622 History of Changes |
Other Study ID Numbers: |
CDR0000437795 DUMC-NCI-7042 NCI-7042 |
First Posted: | August 10, 2005 Key Record Dates |
Last Update Posted: | November 12, 2012 |
Last Verified: | November 2012 |
Keywords provided by H. Kim Lyerly, Duke University Medical Center:
male breast cancer recurrent breast cancer stage IV breast cancer recurrent colon cancer stage IV colon cancer recurrent rectal cancer stage IV rectal cancer |
recurrent pancreatic cancer extensive stage small cell lung cancer recurrent non-small cell lung cancer recurrent small cell lung cancer stage IV non-small cell lung cancer unspecified adult solid tumor, protocol specific stage IV pancreatic cancer |
Additional relevant MeSH terms:
Breast Neoplasms Lung Neoplasms Colorectal Neoplasms Pancreatic Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Respiratory Tract Neoplasms Thoracic Neoplasms Lung Diseases Respiratory Tract Diseases Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms |
Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Endocrine Gland Neoplasms Pancreatic Diseases Endocrine System Diseases Vaccines Metronidazole Denileukin diftitox Interleukin-2 Immunologic Factors Physiological Effects of Drugs Anti-Infective Agents |