Vaccine Therapy in Treating Patients With Liver or Lung Metastases From Colorectal Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Michael Morse, MD, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00103142
First received: February 7, 2005
Last updated: February 28, 2014
Last verified: February 2014
  Purpose

RATIONALE: Vaccines made from a gene-modified virus and a person's white blood cells may make the body build an effective immune response to kill tumor cells. Biological therapies, such as Granulocyte-macrophage colony-stimulating factor (GM-CSF), may stimulate the immune system in different ways and stop tumor cells from growing. Combining different types of biological therapies may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying giving vaccine therapy together with dendritic cells to see how well it works compared to giving vaccine therapy together with GM-CSF in treating patients with liver or lung metastases from colorectal cancer removed by surgery.


Condition Intervention Phase
Colorectal Cancer
Metastatic Cancer
Biological: falimarev
Biological: inalimarev
Biological: sargramostim
Biological: therapeutic autologous dendritic cells
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Active Immunotherapy With PANVAC or Autologous, Cultured Dendritic Cells Infected With PANVAC After Complete Resection of Hepatic or Pulmonary Metastases of Colorectal Carcinoma

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Recurrence-free Survival at 2 Years [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Recurrence-free survival for randomized patients receiving dendritic cells (DC) loaded with PANVAC or PANVAC plus Granulocyte-macrophage colony-stimulating factor (GM-CSF) measured from the date of metastasectomy, with relapse defined as documented disease recurrence at any site.


Secondary Outcome Measures:
  • Positive Immune Response as Measured by (Enzyme-linked Immunosorbent Spot) ELISpot Assay [ Time Frame: 13 weeks ] [ Designated as safety issue: No ]
    CEA-Specific Immune Responders by enzyme-linked immunosorbent spot (ELISpot). The ELISPOT assay is considered positive for a subject if the mean number of spots with CEA exceeds the number of spots with control by a magnitude of 10 and the difference between CEA and control is statistically significant at a level of p=0.05 by the t-test.


Enrollment: 74
Study Start Date: February 2005
Study Completion Date: March 2013
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PANVAC-V + PANVAC-F + DC
Patients undergo leukapheresis to obtain leukocytes for generation of autologous dendritic cells (DC). Patients then receive autologous DC loaded with vaccinia-CEA-MUC-1-TRICOM (PANVAC-V) vaccine subcutaneously (SC) and intradermally (ID) on day 1 and autologous DC loaded with fowlpox-CEA-MUC-1-TRICOM (PANVAC-F) vaccine SC and ID on days 28, 56, and 84.
Biological: falimarev
Given subcutaneously and intradermally
Biological: inalimarev
Given subcutaneously and intradermally
Biological: therapeutic autologous dendritic cells
Given subcutaneously and intradermally
Experimental: PANVAC-V + PANVAC-F + GM-CSF
Patients receive PANVAC-V SC on day 1 and PANVAC-F SC on days 28, 56, and 84. Patients also receive sargramostim (GM-CSF) SC into the same injection site once daily on days 0-3, 28-31, 56-59, and 84-87.
Biological: falimarev
Given subcutaneously and intradermally
Biological: inalimarev
Given subcutaneously and intradermally
Biological: sargramostim
Given subcutaneously

Detailed Description:

OBJECTIVES:

Primary

  • Compare 2-year disease-free survival of patients with completely resected hepatic or pulmonary metastases secondary to colorectal cancer treated with adjuvant vaccine therapy comprising vaccinia-Carcinoembryonic antigen (CEA)-mucin 1 (MUC-1)- Triad of costimulatory molecules TRICOM vaccine (PANVAC-V) and fowlpox-CEA-MUC-1-TRICOM vaccine (PANVAC-F) administered with autologous dendritic cells or with sargramostim (GM-CSF).

Secondary

  • Compare the rate and magnitude of immune response, as determined by enzyme-linked immunosorbent spot (ELISpot), in patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients undergo leukapheresis to obtain leukocytes for generation of autologous dendritic cells (DC). Patients then receive autologous DC loaded with vaccinia-CEA-MUC-1-TRICOM (PANVAC-V) vaccine subcutaneously (SC) and intradermally (ID) on day 1 and autologous DC loaded with fowlpox-CEA-MUC-1-TRICOM (PANVAC-F) vaccine subcutaneously (SC) and intradermally (ID) on days 28, 56, and 84.
  • Arm II: Patients receive PANVAC-V SC on day 1 and PANVAC-F SC on days 28, 56, and 84. Patients also receive sargramostim (GM-CSF) SC into the same injection site once daily on days 0-3, 28-31, 56-59, and 84-87.

After completion of study treatment, patients are followed for 2 years.

PROJECTED ACCRUAL: A total of 72 patients (36 per treatment arm) will be accrued for this study within 2 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed hepatic or pulmonary metastases secondary to adenocarcinoma of the colon and rectum
  • Must have undergone complete resection of hepatic or pulmonary metastases with curative intent

    • No evidence of gross residual disease after surgery
    • One or more resected and ablated lesions allowed provided all gross residual tumor was destroyed by ablation
    • Repeated resections of hepatic metastatic disease or resections of extrahepatic metastases prior to resection of the hepatic metastases allowed provided the most recent hepatic metastatic resection included total disease resection and/or ablation
  • Must have received at least 2 months of perioperative systemic chemotherapy (including preoperative and/or postoperative chemotherapy) that was completed at least 1 month ago

PATIENT CHARACTERISTICS:

Age

  • At least 18

Performance status

  • Karnofsky 70-100%

Life expectancy

  • At least 6 months

Hematopoietic

  • Platelet count ≥ 75,000/mm^3
  • Hemoglobin ≥ 8.5 g/dL (transfusion or epoetin alfa allowed)

Hepatic

  • Bilirubin ≤ 2.0 mg/dL
  • Hepatitis B surface antigen negative
  • Hepatitis C antibody negative
  • No other serious chronic or acute hepatic disease

Renal

  • Creatinine ≤ 1.5 mg/dL OR
  • Creatinine clearance > 60 mL/min

Cardiovascular

  • No New York Heart Association class III or IV cardiac disease
  • No other serious chronic or acute cardiac disease

Pulmonary

  • No asthma
  • No chronic obstructive pulmonary disease
  • No other serious chronic or acute pulmonary disease

Immunologic

  • No history of autoimmune disease, including, but not limited to, any of the following:

    • Inflammatory bowel disease
    • Systemic lupus erythematosus
    • Ankylosing spondylitis
    • Scleroderma
    • Multiple sclerosis
  • No human immunodeficiency virus (HIV) infection by enzyme-linked immunosorbent assay (ELISA) and western blot
  • Not immunocompromised (by disease or therapy)
  • No allergy to eggs or any component of the study vaccine
  • No history of allergy or untoward reaction to prior vaccinia (smallpox) vaccination
  • No allergy or untoward reaction to sargramostim (GM-CSF)
  • No active acute or chronic infection, including urinary tract infection within the past 72 hours
  • No inflammatory bowel conditions, including, but not limited to, the following:

    • Active infectious enteritis
    • Eosinophilic enteritis
  • No acute, chronic, or exfoliative skin disorders, including any of the following:

    • Extensive psoriasis
    • Burns
    • Impetigo
    • Disseminated zoster
    • Varicella zoster
    • Severe acne
    • Other open rashes or wounds

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Able to avoid close contact or household contact for 3 weeks after each vaccination with the following individuals:

    • Children under 5 years of age
    • Pregnant or nursing women
    • Individuals with prior or concurrent extensive eczema, other eczematoid skin disorders, or other acute or chronic skin conditions
    • Immunosuppressed or immunodeficient individuals
  • No medical or psychological condition that would preclude study compliance
  • No extensive eczema
  • No other serious chronic or acute illness that would preclude study participation
  • No other malignancy within the past 5 years except nonmelanoma skin cancer, controlled superficial bladder cancer, or previously treated carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No other concurrent immunotherapy

Chemotherapy

  • See Disease Characteristics
  • No concurrent chemotherapy

Endocrine therapy

  • More than 6 weeks since prior and no concurrent steroid therapy

Radiotherapy

  • No concurrent radiotherapy

Surgery

  • See Disease Characteristics

Other

  • No other concurrent immunosuppressants (e.g., azathioprine or cyclosporine)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00103142

Locations
United States, District of Columbia
Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, United States, 33612-9497
United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, United States, 27157
United States, Oregon
Providence Cancer Center at Providence Portland Medical Center
Portland, Oregon, United States, 97213-2967
United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Sponsors and Collaborators
Michael Morse, MD
Investigators
Study Chair: Michael A. Morse, MD Duke Cancer Institute
  More Information

Additional Information:
No publications provided by Duke University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Michael Morse, MD, Professor of Medicine, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00103142     History of Changes
Other Study ID Numbers: Pro00007616, DUMC-5883-04-6RO, CDR000041079
Study First Received: February 7, 2005
Results First Received: January 16, 2014
Last Updated: February 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Duke University:
liver metastases
adenocarcinoma of the colon
recurrent colon cancer
stage IV colon cancer
adenocarcinoma of the rectum
recurrent rectal cancer
stage IV rectal cancer
lung metastases

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Neoplastic Processes
Pathologic Processes
Rectal Diseases

ClinicalTrials.gov processed this record on October 21, 2014