Denileukin Diftitox Followed by Vaccine Therapy in Treating Patients With Metastatic Cancer

NCT00128622 | Completed Phase 1

• 3 other identifiers: CDR0000437795DUMC-NCI-7042NCI-7042
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

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.

Conditions

Breast Cancer; Colorectal Cancer; Lung Cancer; Pancreatic Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Safety as measured by rate of adverse events during study drug treatment

  3 months

Secondary Outcomes (1)

• Rate of immune response as measured by ELISPot at week 10

  3 months

Study Arms (1)

Denileukin Diftitox plus vaccine

EXPERIMENTAL

This is a single arm Phase I safety study.

Biological: denileukin diftitox; Biological: recombinant fowlpox-CEA(6D)/TRICOM vaccine; Biological: therapeutic autologous dendritic cells

Interventions

denileukin diftitox BIOLOGICAL

Denileukin Diftitox plus vaccine

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

Denileukin Diftitox plus vaccine

therapeutic autologous dendritic cells BIOLOGICAL

Denileukin Diftitox plus vaccine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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: 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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• H. Kim Lyerly: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Lombardi Comprehensive Cancer Center at Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Related Publications (2)

• Schonfeld K, Mahnke K, Schallenberg S, et al.: Treatment of melanoma bearing individuals with ONTAK® depletes regulatory T cells resulting in an augmented immune response following vaccination. [Abstract] J Invest Dermatol 126 (Suppl S3): A-594, s101, 2006.

  BACKGROUND

• Morse MA, Hobeika AC, Osada T, Serra D, Niedzwiecki D, Lyerly HK, Clay TM. Depletion of human regulatory T cells specifically enhances antigen-specific immune responses to cancer vaccines. Blood. 2008 Aug 1;112(3):610-8. doi: 10.1182/blood-2008-01-135319. Epub 2008 Jun 2.

  PMID: 18519811 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Colorectal Neoplasms; Lung Neoplasms; Pancreatic Neoplasms; Breast Neoplasms, Male; Colonic Neoplasms; Rectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma

Interventions

denileukin diftitox

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Study Officials

• Michael A. Morse, MD

  Duke Cancer Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Gen & Thor Surgery

Study Record Dates

• First Submitted: August 8, 2005
• First Posted: August 10, 2005
• Study Start: September 1, 2005
• Primary Completion: March 1, 2007
• Study Completion: May 1, 2009
• Last Updated: November 12, 2012

Record last verified: 2012-11

Locations

US (2)