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Active Immunization of Patients With Carcinoma of Oral Cavity or Oropharynx With Autologous Dendritic Cells Transfected With DNA From Autologous Tumor

Primary Purpose

Primary Advanced Carcinoma of the Oral Cavity or Oropharynx, Squamous Cell Carcinoma of the Head and Neck

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

autologous monocyte-derived dendritic cells (DC) transfected with DNA

About this trial

This is an interventional treatment trial for Primary Advanced Carcinoma of the Oral Cavity or Oropharynx focused on measuring Carcinoma, Head, Neck, Oral Cavity, Oropharynx, Mouth

Eligibility Criteria

37 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Written informed consent conforming to the institutional guidelines obtained from the patient.

Documented evidence of oral carcinoma or carcinoma of the oropharynx. Patients will undergo surgery, surgery and radiation or chemoradiation therapy, and will become eligible for the first vaccine between 1and 4 months after termination of conventional therapy.

Adequate immune competence, as indicated by positive reaction to one or more of the DTH skin tests.

Age 18 or above. Karnofsky performance status > 70% and life expectancy > eight months.

Adequate hematologic function:

Absolute neutrophil count > 1,000/mm3 Absolute lymphocyte count > 1,000/mm3 Hemoglobin > 9 g/dl Platelets > 100,000/mm3 h) Liver function tests: Bilirubin (total) < 1.7 mg/dl Alkaline phosphatase < 78 u/L (2 x ULN) SGOT < 54 u/L (2 x ULN) Lactic dehydrogenase < 180 u/L (2 x ULN) i) Kidney profile: Serum electrolytes Sodium 135-145 mEq/L Potassium 3.5-5.0 mEq/L Bicarbonate 21-28 mEq/L Chloride 100-108 mmol/L 2) Serum creatinine <4.5 mg/dL (3 x ULN) 3) BUN 8-25 mg/dL j) At least four weeks since any prior radiation therapy, immunotherapy, or chemotherapy

Exclusion Criteria:

- One or more of the Inclusion Criteria are not met. A significant history or current evidence of cardiac disease including, but not limited to, congestive heart failure, coronary artery disease, angina pectoris, uncontrolled hypertension, serious arrhythmias; or myocardial infarction within the previous six months.

Evidence of active infection requiring antibiotic therapy. Positive HIV or Hepatitis B or C screen tests Active intracranial metastases. Previously resected intracranial disease and or previously irradiated intracranial metastases which have been stable for four weeks are eligible.

History of other concurrent malignancies except basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.

Pregnant or lactating women. Patients requiring systemic corticosteroids (unless patient has had NO STEROIDS IN THE PAST 4 WEEKS).

Autoimmune disease including, but not limited to, rheumatoid arthritis, systemic lupus erythematous, multiple sclerosis, or ankylosing spondylitis

Sites / Locations

University of Pittsburgh Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dendritic Cells w/Tumor DNA

Arm Description

Outcomes

Primary Outcome Measures

To determine the safety and feasibility of immunization of patients with the carcinomas of the oral cavity or the oropharynx with autologous DCs nucleofected with tumor DNA obtained from the patient's own tumor.

Secondary Outcome Measures

To determine whether the immunological responses to the vaccine and/or antitumor immune responses can be induced in patients who receive the vaccine

Full Information

NCT ID

NCT00377247

First Posted

September 14, 2006

Last Updated

July 7, 2016

Sponsor

University of Pittsburgh

1. Study Identification

Unique Protocol Identification Number

NCT00377247

Brief Title

Active Immunization of Patients With Carcinoma of Oral Cavity or Oropharynx With Autologous Dendritic Cells Transfected With DNA From Autologous Tumor

Official Title

Active Immunization of Patients With Carcinoma of Oral Cavity or Oropharynx With Autologous Dendritic Cells Transfected With DNA From Autologous Tumor (Phase I/II Study)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2016

Overall Recruitment Status

Terminated

Why Stopped

study closed to accrual due to slow accrual

Study Start Date

April 2009 (undefined)

Primary Completion Date

April 2009 (Actual)

Study Completion Date

April 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Pittsburgh

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The primary goal of this study is to determine if the vaccine can be safely given to subjects, and to see what side effects occur (both good and bad) when they are given this experimental tumor vaccine. During this study, investigators intend to watch for tumor response while examining the effects of this vaccine on the body's immune system after it is given.

Detailed Description

This is an uncontrolled, non-randomized trial to evaluate safety, immunogenicity and feasibility of a new vaccine, consisting of autologous monocyte-derived dendritic cells (DC) transfected with autologous tumor-derived DNA. Briefly, the plan is to use a two-stage trial design and to initially enroll 17 patients with primary advanced carcinoma of the oral cavity or oropharynx over a period of 2 years. The patients will undergo surgery, and a portion of the primary tumor specimen not necessary for the pathologic diagnosis will be obtained to serve as a source of tumor DNA. Each DC-based vaccine will contain DNA-transfected DC. It will be administered intranodally under ultrasound guidance. Only those patients who have normal delayed type hypersensitivity (DTH) responses to recall antigens will be eligible to receive the vaccine. Immunologic response to the vaccine will be evaluated. If there is no evidence of toxicity, and >3 patients show immunologic response, the second stage of the study will be opened for accrual of 22 patients. All patients will be monitored by interferon- gamma (IFN-) secretion in enzyme-linked immunospot (ELISPOT) assays prior to and after vaccination for the frequency of T-cells responsive to autologous tumor and to the vaccine. The patients will also be evaluated before and after vaccination for the capability of their T cells to respond to activating signals delivered via the T cell receptor (TcR). Primary Objective: To determine the safety and feasibility of immunization of patients with carcinoma of the oral cavity or oropharynx with autologous monocyte-derived dendritic cells (DC) transfected with DNA obtained from the patient's own cancer cells. Secondary Objective: To evaluate the ability of the DNA-based DC vaccine to induce immune responses to the vaccine as well as to autologous tumor.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Primary Advanced Carcinoma of the Oral Cavity or Oropharynx, Squamous Cell Carcinoma of the Head and Neck

Keywords

Carcinoma, Head, Neck, Oral Cavity, Oropharynx, Mouth

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

5 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dendritic Cells w/Tumor DNA

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

autologous monocyte-derived dendritic cells (DC) transfected with DNA

Intervention Description

The patients will receive 1 x 107 DC/vaccine delivered intranodally or perinodally to lymph nodes (LN) distant from the head and neck area (e.g., to inguinal LN)

Primary Outcome Measure Information:

Title

Time Frame

6 months

Secondary Outcome Measure Information:

Title

To determine whether the immunological responses to the vaccine and/or antitumor immune responses can be induced in patients who receive the vaccine

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

37 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: - Written informed consent conforming to the institutional guidelines obtained from the patient. Documented evidence of oral carcinoma or carcinoma of the oropharynx. Patients will undergo surgery, surgery and radiation or chemoradiation therapy, and will become eligible for the first vaccine between 1and 4 months after termination of conventional therapy. Adequate immune competence, as indicated by positive reaction to one or more of the DTH skin tests. Age 18 or above. Karnofsky performance status > 70% and life expectancy > eight months. Adequate hematologic function: Absolute neutrophil count > 1,000/mm3 Absolute lymphocyte count > 1,000/mm3 Hemoglobin > 9 g/dl Platelets > 100,000/mm3 h) Liver function tests: Bilirubin (total) < 1.7 mg/dl Alkaline phosphatase < 78 u/L (2 x ULN) SGOT < 54 u/L (2 x ULN) Lactic dehydrogenase < 180 u/L (2 x ULN) i) Kidney profile: Serum electrolytes Sodium 135-145 mEq/L Potassium 3.5-5.0 mEq/L Bicarbonate 21-28 mEq/L Chloride 100-108 mmol/L 2) Serum creatinine <4.5 mg/dL (3 x ULN) 3) BUN 8-25 mg/dL j) At least four weeks since any prior radiation therapy, immunotherapy, or chemotherapy Exclusion Criteria: - One or more of the Inclusion Criteria are not met. A significant history or current evidence of cardiac disease including, but not limited to, congestive heart failure, coronary artery disease, angina pectoris, uncontrolled hypertension, serious arrhythmias; or myocardial infarction within the previous six months. Evidence of active infection requiring antibiotic therapy. Positive HIV or Hepatitis B or C screen tests Active intracranial metastases. Previously resected intracranial disease and or previously irradiated intracranial metastases which have been stable for four weeks are eligible. History of other concurrent malignancies except basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix. Pregnant or lactating women. Patients requiring systemic corticosteroids (unless patient has had NO STEROIDS IN THE PAST 4 WEEKS). Autoimmune disease including, but not limited to, rheumatoid arthritis, systemic lupus erythematous, multiple sclerosis, or ankylosing spondylitis

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jonas T Johnson, M.D.

Organizational Affiliation

UMPC/UPCI

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Pittsburgh Cancer Institute

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15213

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Active Immunization of Patients With Carcinoma of Oral Cavity or Oropharynx With Autologous Dendritic Cells Transfected With DNA From Autologous Tumor

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