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

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Experimental therapy consists of leukapheresis which is the separation and removal of leukocytes from withdrawn blood, frozen for later use.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	Biological: Dendritic cell injections Procedure: Radiation therapy Procedure: Surgery for tumor removal	Phase II

MedlinePlus related topics: Cancer Radiation Therapy Soft Tissue Sarcoma Surgery

Drug Information available for: Phenylephrine Phenylephrine hydrochloride Oxymetazoline Oxymetazoline hydrochloride

U.S. FDA Resources

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 Outcome Measures:

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. [ Time Frame: dependent upon results ] [ Designated as safety issue: Yes ]
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. [ Time Frame: dependent upon results ] [ Designated as safety issue: Yes ]
Assess the toxicity of the investigational treatment, and the primary tumor responses. [ Time Frame: dependent upon results ] [ Designated as safety issue: Yes ]
Analysis of DC migration will compare the ratio of radioactive count within lymph nodes and the tumor site to the background counts. [ Time Frame: dependent upon results ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	22
Study Start Date:	June 2006
Estimated Study Completion Date:	July 2010
Estimated Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Group 1 will receive vaccine injection 1 day before surgery	Biological: Dendritic cell injections Day 19: #2 DC injection Day 26: #3 DC injection # 4 DC injection: patients will be assigned to one of three cohorts: Group 1 - DC injection # 4 given 24 hours prior to surgery Group 2 - DC injection # 4 given 48 hours prior to surgery Group 3 - DC injection # 4 given 72 hours prior to surgery Procedure: Radiation therapy Radiation therapy will be coordinated to ensure that adequate apoptosis is ongoing within the soft tissue sarcoma at the time of intratumoral dendritic cell injection. Procedure: Surgery for tumor removal 3 - 5 weeks after the last external radiation treatment, patients will undergo surgery to remove the tumor.
2: Active Comparator Group 2 will receive vaccine 2 days before surgery	Biological: Dendritic cell injections Day 19: #2 DC injection Day 26: #3 DC injection # 4 DC injection: patients will be assigned to one of three cohorts: Group 1 - DC injection # 4 given 24 hours prior to surgery Group 2 - DC injection # 4 given 48 hours prior to surgery Group 3 - DC injection # 4 given 72 hours prior to surgery Procedure: Radiation therapy Radiation therapy will be coordinated to ensure that adequate apoptosis is ongoing within the soft tissue sarcoma at the time of intratumoral dendritic cell injection. Procedure: Surgery for tumor removal 3 - 5 weeks after the last external radiation treatment, patients will undergo surgery to remove the tumor.
3: Active Comparator Group 3 will receive vaccine 3 days before surgery	Biological: Dendritic cell injections Day 19: #2 DC injection Day 26: #3 DC injection # 4 DC injection: patients will be assigned to one of three cohorts: Group 1 - DC injection # 4 given 24 hours prior to surgery Group 2 - DC injection # 4 given 48 hours prior to surgery Group 3 - DC injection # 4 given 72 hours prior to surgery Procedure: Radiation therapy Radiation therapy will be coordinated to ensure that adequate apoptosis is ongoing within the soft tissue sarcoma at the time of intratumoral dendritic cell injection. Procedure: Surgery for tumor removal 3 - 5 weeks after the last external radiation treatment, patients will undergo surgery to remove the tumor.

Detailed Description:

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
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00365872

Locations

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

Sponsors and Collaborators

H. Lee Moffitt Cancer Center and Research Institute

Cancer Treatment Research Foundation

Investigators

Principal Investigator:

Scott Antonia, M.D.

H. Lee Moffitt Cancer Center and Research Institute

More Information

Additional Information:

Active Clinical Trials at Moffitt Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	H. Lee Moffitt Cancer Center and Research Institute, Inc. ( Scott Antonia, M.D. )
Study ID Numbers:	MCC-14497, BB-IND 10005, IRB 104007
Study First Received:	August 17, 2006
Last Updated:	April 13, 2009
ClinicalTrials.gov Identifier:	NCT00365872 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:

Sarcoma
Intratumoral injection
Dendritic cells
Neo-adjuvant treatment

Immunotherapy
Pheresis
Radiation

Study placed in the following topic categories:

Oxymetazoline
Neoplasms, Connective and Soft Tissue
Soft Tissue Sarcomas
Malignant Mesenchymal Tumor

Phenylephrine
Adjuvants, Immunologic
Sarcoma

Additional relevant MeSH terms:

Neoplasms, Connective and Soft Tissue
Neoplasms
Neoplasms by Histologic Type
Sarcoma

ClinicalTrials.gov processed this record on May 06, 2009