Vaccination of Patients With Ovarian Cancer With Dendritic Cell/Tumor Fusions With Granulocyte Macrophage Colony-stimulating Factor (GM-CSF) and Imiquimod - Full Text View

Sponsors and Collaborators:	Beth Israel Deaconess Medical Center Dana-Farber Cancer Institute Brigham and Women's Hospital Massachusetts General Hospital National Cancer Institute (NCI)
Information provided by:	Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00799110

Purpose

This research study is evaluating the effect (good and bad) of a dendritic cell/tumor fusion vaccine in combination with the laboratory made agents GM-CSF and imiquimod on the participants immune system. Another purpose of this study is to determine the type and severity of any side effects associated with this new study vaccine. We will also be evaluating what effect the vaccine has on the participants cancer. Dendritic cell vaccines have already been tested in clinical trials involving participants with many different types of cancer.

Dendritic cells are powerful immune-stimulating cells that are normally found in small amounts in the body and are responsible for immune responses against "foreign" substances that enter the body.

Condition	Intervention	Phase
Ovarian Cancer Primary Peritoneal Cancer Fallopian Tube Cancer	Drug: GM-CSF Biological: Dendritic Cell/Tumor Fusion Vaccine Drug: imiquimod	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Safety Study
Official Title:	Vaccination of Patients With Ovarian Cancer With Dendritic Cell/Tumor Fusions With GM-CSF and Imiquimod

Resource links provided by NLM:

MedlinePlus related topics: Cancer Ovarian Cancer

Drug Information available for: Granulocyte-macrophage colony-stimulating factor S 26308 Sargramostim

U.S. FDA Resources

Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:

To determine if cellular immunity is induced by serial vaccination with DC/tumor fusion cells, when given with GM-CSF alone, or the combination of GM-CSF and imiquimod in this patient population. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To assess toxicity associated with vaccination with DC/tumor fusion when given with GM-CSF and imiquimod. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To assess clinical response to vaccination with DC/tumor fusion when given with GM-CSF and imiquimod. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To correlate immunologic response following vaccination with measures of patient cellular immune function and phenotypic characteristics of the vaccine preparation. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	23
Study Start Date:	August 2008
Estimated Primary Completion Date:	August 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group 2: Experimental Vaccine, GM-CSF and imiquimod,	Drug: GM-CSF Injections given subcutaneously at the sight of vaccination on the day of the vaccination and for three days afterwards Biological: Dendritic Cell/Tumor Fusion Vaccine Given subcutaneously once every three weeks for a total of three vaccines Drug: imiquimod Cream applied to the skin at the injection sight 2 hours before injection and for 3 days following the injection
Group 1: Experimental Vaccination plus GM-CSF	Drug: GM-CSF Injections given subcutaneously at the sight of vaccination on the day of the vaccination and for three days afterwards Biological: Dendritic Cell/Tumor Fusion Vaccine Given subcutaneously once every three weeks for a total of three vaccines

Detailed Description:

Patients must have undergone therapeutic debulking surgery for independent clinical indications and have tissue frozen and stored under sterile conditions as part of protocol 07-319 (Study of Primary Tumor Harvest for the Purpose of Possible Use in a Future Clinical Trial in Patients with Ovarian, Fallopian Tube, or Primary Peritoneal Cancer)
Participants will be assigned to one of two study groups. Both groups will undergo a procedure known as leukapheresis by which the white blood cells are removed from the participants blood in order to obtain the dendritic cells. Prior to this procedure participants may receive 4 injections of GM-CSF, which helps increase the white blood cell count.
If enough cells are obtained during the leukapheresis, tumor cells and dendritic cells will then be fused (mixed) together in the laboratory and divided into the appropriate doses for administration.
Participants assigned to Group 1 will undergo subcutaneous vaccination with the dendritic cell tumor fusion vaccine. On the day of the vaccine and three days afterwards, they will receive GM-CSF injections at the site of the vaccination. Participants will receive a dose of the vaccine every 3 weeks for a total of 3 vaccinations.
Participants assigned to Group 2 will undergo subcutaneous vaccination with the dendritic cell tumor fusion vaccine. On the day of the vaccine and three days afterwards, they will receive GM-CSF injection at the site of the vaccination. Additionally, imiquimod cream will be applied to the skin at the injection sight 2 hours before the vaccine administration. Participants will continue to apply imiquimod cream at the site of vaccination for 3 days following the injection. Participants will receive a dose of the vaccine every 3 weeks for a total of 3 vaccinations.

Eligibility

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

Criteria

Inclusion criteria at time of initial enrollment:

Patients must have undergone therapeutic debulking surgery for independent clinical indications and have tissue frozen and stored under sterile conditions as part of protocol 07-319 (Study of Primary Tumor Harvest for the Purpose of Possible Use in a Future Clinical Trial in Patients with Ovarian, Fallopian Tube, or Primary Peritoneal Cancer)
Patients with histologically proven stage III or IV ovarian, fallopian tube or primary peritoneal serous carcinoma (or patients of any stage with recurrent disease) who demonstrate lack of disease progression as determined by clinical assessment as well as CA-125 levels and/or radiographic assessment
Patients must have ECOG performance status of 0-2 with greater than six week life expectancy.
All patients must be informed of the investigational nature of this study and must give written informed consent in accordance with institutional and federal guidelines.
Laboratories:WBC > 2.0 X 103/uL, Platelets > 50,000/uL, Bilirubin < 2.0 mg/dL, Creatinine <2.0 mg/dL, AST/ALT < 2.5 x ULN

Eligibility criteria prior to first vaccination At a maximum of twelve weeks after the last dose of chemotherapy, patients must fulfill the following criteria:

Complete clinical response after first-line chemotherapy for newly-diagnosed patients, or after second-line chemotherapy for relapsed patients who require secondary cytoreduction.**
Asymptomatic, low volume disease not requiring further chemotherapy prior to initiating vaccination
- Complete clinical response is defined as normal exam, normal CT scan, and normal CA-125 level. Tumor tissue for relapsed patients would be obtained under informed consent at the time of a secondary surgical debulking, which would be performed as part of standard relapse management in appropriate patients.
Resolution of all chemotherapy related grade III-IV toxicity
Laboratories:WBC > 2.0 X 103/uL, Platelets > 50,000/uL, Bilirubin < 2.0 mg/dL Creatinine <2.0 mg/dL, AST/ALT < 2.5 x ULN

Exclusion Criteria:

Patient with progressive disease during first line chemotherapy with a platinum/taxane combination will be excluded.
Patients must not have clinically significant autoimmune disease that requires treatment with immunosuppressant medications.
Because of compromised cellular immunity and limited capacity to respond to vaccination, patients who are HIV+ will be excluded.
Patients must not have serious intercurrent illness such as infection requiring IV antibiotics, or significant cardiac disease characterized by significant arrhythmia, unstable ischemic coronary disease or congestive heart failure.
Pregnant and/or lactating women will be excluded. Premenopausal patients will undergo pregnancy testing when indicated. Women will practice effective birth control while receiving protocol treatment.
Patients with a history of clinically significant venous thromboembolism will be excluded.
Active second malignancy, aside from basal cell or squamous cell carcinoma of the skin (i.e. malignancy not treated with curative intent or diagnosis within the past 2 years)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00799110

Contacts

Contact: David Avigan, MD	617-667-9920	davigan@bidmc.harvard.edu
Contact: Dilani Dombagoda	617-667-5984	ddombago@bidmc.harvard.edu

Locations

United States, Massachusetts
Beth Israel Deaconess Medical Center	Recruiting
Boston, Massachusetts, United States, 02215
Contact: David Avigan, MD 617-667-9920 davigan@bidmc.harvard.edu
Contact: Dilani Dombagoda 617-667-5984 ddombago@bidmc.harvard.edu
Principal Investigator: David Avigan, MD
Sub-Investigator: Jacalyn Rosenblatt, MD
Sub-Investigator: Lynne Uhl, MD
Sub-Investigator: Stephen Cannistra, MD
Dana-Farber Cancer Institute	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Ursula Matulonis, MD 617-632-2334 umatulonis@partners.org
Principal Investigator: Ursula Matulonis, MD
Sub-Investigator: Donald Kufe, MD
Sub-Investigator: Susan Berlin, MD
Sub-Investigator: Susana Campos, MD
Sub-Investigator: Marcus Butler, MD
Massachusetts General Hospital	Recruiting
Boston, Massachusetts, United States, 02114
Contact: Carolyn Krasner, MD 617-726-1941 pdicicco@partners.org
Principal Investigator: Carolyn Krasner, MD
Sub-Investigator: Richard Penson, MD
Sub-Investigator: Marcela Del Carmen, MD
Sub-Investigator: AK Goodman, MD
Brigham & Women's Hospital	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Ross Berkowitz, MD 617-732-8843 rberkowitz@partners.org
Sub-Investigator: Ross Berkowitz, MD
Sub-Investigator: Neil Horowitz, MD
Sub-Investigator: Michael Muto, MD
Sub-Investigator: Colleen Feltmate, MD

Sponsors and Collaborators

Beth Israel Deaconess Medical Center

Dana-Farber Cancer Institute

Brigham and Women's Hospital

Massachusetts General Hospital

National Cancer Institute (NCI)

Investigators

Principal Investigator:

David Avigan, MD

Beth Israel Deaconess Medical Center

More Information

No publications provided

Responsible Party:	Beth Isreal Deaconess Medical Center ( David Avigan, MD )
Study ID Numbers:	07-380
Study First Received:	November 26, 2008
Last Updated:	August 4, 2009
ClinicalTrials.gov Identifier:	NCT00799110 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:

dendritic cells
fusion vaccines
GM-CSF
imiquimod

Study placed in the following topic categories:

Fallopian Tube Cancer
Ovarian Neoplasms
Immunologic Factors
Gonadal Disorders
Interferons
Adjuvants, Immunologic
Genital Neoplasms, Female
Endocrine System Diseases

Urogenital Neoplasms
Imiquimod
Ovarian Diseases
Fallopian Tube Neoplasms
Genital Diseases, Female
Ovarian Cancer
Endocrinopathy
Endocrine Gland Neoplasms

Additional relevant MeSH terms:

Interferon Inducers
Ovarian Neoplasms
Immunologic Factors
Antineoplastic Agents
Gonadal Disorders
Physiological Effects of Drugs
Adjuvants, Immunologic
Genital Neoplasms, Female
Endocrine System Diseases
Imiquimod
Urogenital Neoplasms

Ovarian Diseases
Pharmacologic Actions
Fallopian Tube Neoplasms
Adnexal Diseases
Fallopian Tube Diseases
Genital Diseases, Female
Neoplasms
Neoplasms by Site
Therapeutic Uses
Endocrine Gland Neoplasms

ClinicalTrials.gov processed this record on September 10, 2009