Combination of External Beam Radiation With Intratumoral Injection of Dendritic Cells as Neo-adjuvant Treatment of High-risk Soft Tissue Sarcoma Patients
18 Years
N/A
Both
Soft Tissue Sarcoma
Trial Information
Combination of External Beam Radiation With Intratumoral Injection of Dendritic Cells as Neo-adjuvant Treatment of High-risk Soft Tissue Sarcoma Patients
Pre-treatment test will consist of a blood draw for anti-tumor immune response and Hepatitis
B, Hepatitis C, Human Immunodeficiency Virus (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 Common Terminology Criteria (CTC). 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.
Patients 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 computed tomography
(CT) scan of chest and magnetic resonance imaging (MRI) scan of extremity will be performed
at every office visit.
Inclusion Criteria:
- Intermediate or high grade sarcoma as determined by pathology review
- Musculoskeletal tumor in extremities, trunk or chest wall.
- Primary tumor or isolated locally recurrent tumor greater than 5 cm in diameter.
- Clinical Stage T2N0M0 (AJCC 6th edition)
- Patient is not a candidate for neoadjuvant chemotherapy.
- Performance status Eastern Cooperative Oncology Group (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).
- White blood count (WBC) > 3,000/mm to the third power and absolute neutrophil
count (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
- Radiation Oncologist must confirm that a 2-3 cm strip of skin can be spared from
radiation.
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.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Effect of Combined Neo-Adjuvant Treatment with Apoptosis-Inducing Therapy
Outcome Description:
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.
Outcome Time Frame:
Average of 6 Months
Safety Issue:
No
Principal Investigator
Scott Antonia, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
H. Lee Moffitt Cancer Center and Research Institute
Authority:
United States: Food and Drug Administration
Study ID:
MCC-14497
NCT ID:
NCT00365872
Start Date:
June 2006
Completion Date:
June 2012
Related Keywords:
- Soft Tissue Sarcoma
- Sarcoma
- Intratumoral injection
- Dendritic cells
- Neo-adjuvant treatment
- Immunotherapy
- Pheresis
- Radiation
- Sarcoma
Name | Location |
|---|---|
| H. Lee Moffitt Cancer Center & Research Institute | Tampa, Florida 33612 |
