http://www.clinicaltrials.gov/ct/show/NCT00365872?order=37

External Beam Radiation With Intratumoral Injection Of Dendritic Cells As Neo-Adjuvant Treatment for Sarcoma

This study is currently recruiting patients.
Verified by H. Lee Moffitt Cancer Center and Research Institute August 2006
Sponsors and Collaborators:     H. Lee Moffitt Cancer Center and Research Institute
Cancer Treatment Research Foundation
Information provided by:     H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:     NCT00365872

Purpose

This is a Phase II study using a combination of external beam radiation with intratumoral injection of dendritic cells (white blood cells) as neo-adjuvant treatment for patients with high-risk soft tissue sarcoma. The purpose is to determine if an injection of the patient’s own immune related white blood cells into their tumor will strengthen the immune system to fight against their cancer.

Pre-treatment tests include a blood draw for anti-tumor immune response and Hepatitis B, Hepatitis C, HIV tests. Labs are drawn for baseline immunity assays; pre-treatment biopsy with collection of tumor cells, immunological studies, surgical specimen and post-therapy immunity assays.

Conventional therapy on day 1 is the external beam radiation which will be delivered in 25 equal fractions – daily for 5 days (M-F) over a 5-week period. Experimental therapy consists of leukapheresis which is the separation and removal of leukocytes from withdrawn blood, frozen for later use. There will be four DC injections occurring during the course of the external beam radiation therapy.

DCs will be labeled (with a radioisotope) and injected intratumorally before surgery. You will be randomized into one of three groups. One group will receive injection of labeled DCs 72 hrs before surgery, second group – 48 hrs, and third group 24 hrs before surgery. On day 50 of treatment,surgery will be performed to remove the tumor.

Results will be correlated with the level of specific immune response. If the experimental treatment causes a measurable change in the immune blood tests, there will be office visits, every 3 months for 2 years. In the longer term, there will be office visits at 6 month intervals for the third year, and yearly thereafter. A CT scan of chest and MRI scan of extremity will be performed at every office visit.
Condition     Intervention     Phase
Soft Tissue Sarcoma
     Vaccine: Dendritic cell injections
 Procedure: Radiation therapy
 Procedure: Surgery for tumor removal
    Phase II

MedlinePlus related topics:  Soft Tissue Sarcoma
Genetics Home Reference related topics:  Soft Tissue Sarcoma

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Official Title: Combination of External Beam Radiation With Intratumoral Injection of Dendritic Cells as Neo-Adjuvant Treatment of High-Risk Soft Tissue Sarcoma Patients
Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:
Primary Outcomes: Determine if combined neo-adjuvant treatment with apoptosis-inducing therapy (gamma-irradiation) plus intratumoral DC administration will induce a T lymphocyte immune response specific for soft tissue sarcoma associated antigens.; Study the functional activity of T cells, as well as the presence, and function of DCs in patients treated with combined administration of apoptosis-inducing agents and DCs.; Assess the toxicity of the investigational treatment, and the primary tumor responses.; Analysis of DC migration will compare the ratio of radioactive count within lymph nodes and the tumor site to the background counts.
Expected Total Enrollment:  22

Study start: June 2006

This is a Phase II study using a combination of external beam radiation with intratumoral injection of dendritic cells (white blood cells) as neo-adjuvant treatment for patients with high-risk soft tissue sarcoma. The purpose is to determine if an injection of the patient’s own immune related white blood cells into their tumor will strengthen the immune system to fight against their cancer.

Pre-treatment test will consist of a blood draw for anti-tumor immune response and Hepatitis B, Hepatitis C, HIV tests. A biopsy with collection of tumor cells. Assays (ELISPOT and flow cytometry) to test for the intended anti-tumor cell T cell response will be performed on biopsy specimens as well as standard pathology department review of specimens for diagnosis and assessment of necrosis and apoptosis. Labs are also drawn for surgical specimens and post-therapy immunity assays.

Prior to commencing therapy, a procedure called leukapheresis (peripheral blood mononuclear cell) isolation will be conducted and twenty-four hours prior to intended injection, the dendritic cells will be harvested and assessed for quality control. Prior to injection (the clinical target is the gross tumor), history and physical examination will be performed. Toxicity will be assessed according to CTC criteria. The plan will be to inject the entire dendritic cell product evenly throughout the tumor.

Conventional therapy consists of external beam radiation therapy, 25 fractions from day 1-33 administered Monday through Friday only. The experimental therapy, dendrite cell (DC) injections will occur during the course of the external beam radiation therapy. DC injections will be prepared from frozen white blood cells and injected at four intervals on day 12, 19, 26, and day 33.

DCs will be labeled (with a radioisotope) and injected intratumorally before surgery. You will be randomized into one of three groups. One group will receive injection of labeled DCs 72 hrs before surgery, second group – 48 hrs, and third group 24 hrs before surgery. Surgery will occur on day 50 for tumor removal.

If the experimental treatment causes a measurable change in the immune blood tests, there will be office visits, every 3 months for 2 years. In the longer term, there will be office visits at 6 month intervals for the third year, and yearly thereafter. A CT scan of chest and MRI scan of extremity will be performed at every office visit.

Eligibility
Genders Eligible for Study:  Both
Criteria

Inclusion Criteria:

    * Histologically diagnosed high-grade (intermediate or high grade) soft tissue sarcoma of clinical and radiographic histological lineage.
    * Musculoskeletal tumor in extremities, trunk or chest wall.
    * Primary tumor or isolated locally recurrent tumor greater than 5 cm in diameter.
    * Clinical Stage T2N0M0 or T3N0M0
    * Patient is not a candidate for neoadjuvant chemotherapy.
    * Performance status ECOG 0 or 1.
    * No steroid therapy within 4 weeks of first dendritic cell administration.
    * No coagulation disorder.
    * Patient’s written informed consent.
    * No contraindication to resection.
    * Adequate organ function (measured within a week of beginning treatment).
    * WBC > 3,000/mm to the third power and ANC >1500/mm to the third power
    * Platelets > 100,000/mm to the third power
    * Hematocrit > 25%
    * Bilirubin < 2.0 mg/dL
    * Creatinine < 2.0 mg/dL, or creatinine clearance > 60 mL/min

Exclusion Criteria:

    * Retroperitoneal location.
    * Gastrointestinal stromal tumor (GIST).
    * Demonstrated metastatic disease.
    * Prior radiation therapy if the current tumor is locally recurrent after prior resection.
    * Concurrent treatment with any anticancer agent other than radiation as dictated by the protocol.
    * Bleeding disorder.
    * H.I.V. infection or other primary immunodeficiency disorder.
    * Ongoing systemic therapy with immunosuppressant drugs (e.g. corticosteroids, azathioprine, cyclosporin, methotrexate).
    * Any serious ongoing infection.
    * Pregnant or lactating women -- Patients in reproductive age must agree to use contraceptive methods for the duration of the study (a pregnancy test will be obtained before treatment).
    * ECOG performance status of 2, 3 or 4.

Location and Contact Information
Please refer to this study by ClinicalTrials.gov identifier  NCT00365872

Mary N Dunn, CRN      813-745-8356    dunnmn@moffitt.usf.edu

Florida
      H. Lee Moffitt Cancer Center & Research Institute, Tampa,  Florida,  33612,  United States; Completed

      H Lee Moffitt Cancer Center & Research Institute, Tampa,  Florida,  33612,  United States; Recruiting

Study chairs or principal investigators

Scott Antonia, M.D.,  Principal Investigator,  H. Lee Moffitt Cancer Center and Research Institute  

More Information

Active Clinical Trials at Moffitt Cancer Center

Study ID Numbers:  MCC-14497
Last Updated:  August 18, 2006
Record first received:  August 17, 2006
ClinicalTrials.gov Identifier:  NCT00365872
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2006-09-25