Radiation Therapy and Intratumoral Autologous Dendritic Cells in Soft Tissue Sarcomas (STS)

Study Overview
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Brief Summary
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The purpose of this study is to determine if injection of the participant's our own immune related white blood cells (called dendritic cells) into their tumor will strengthen their immune system to fight against their cancer.

Official Title
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A Phase II Study Evaluating Neoadjuvant Administration of High Dose Radiation Therapy and Intratumoral Autologous Dendritic Cells in Patients With High-risk Soft Tissue Sarcomas

Conditions
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Soft Tissue Sarcoma

Intervention / Treatment
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* Procedure: External Beam Radiation Therapy (RT)
* Biological: Autologous Dendritic Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Intermediate or High grade (AJCC 7th edition Grade 3 and 4 or Grade 2 and 3 of a 3 tier system) STS as determined by local pathology diagnostic biopsy specimen review Musculoskeletal tumor in extremities, trunk or chest wall Primary tumor or isolated locally recurrent tumor greater than 5 cm in diameter as measured by Response Evaluation Criteria In Solid Tumors (RECIST) criteria v1.1 Clinical Stage T2N0M0 (AJCC 7th edition) Age ≥18 years at time of consent Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of 0 or 1 Patient's written study specific, Institutional Review Board (IRB) stamped informed consent. Adequate organ function (measured within a week prior to beginning treatment for Arm B and within 2 weeks of beginning treatment for Arm A): white blood count (WBC) > 3,000/mm³ and absolute neutrophil count (ANC) >1500/mm³; Platelets > 100,000/mm³; 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 RT. Exclusion Criteria: Retroperitoneal or Head and Neck primary locations Gastrointestinal stromal tumor (GIST) Demonstrated metastatic disease Contraindication to resection Prior RT if the current tumor is locally recurrent after prior resection Concurrent treatment with any anticancer agent other than RT as dictated by the protocol Prior chemotherapy for the pre-surgical treatment of the primary tumor (neoadjuvant chemotherapy)Bleeding/coagulation disorder Human Immunodeficiency Virus (HIV) infection or other primary immunodeficiency disorder Ongoing systemic therapy with immunosuppressant drugs (e.g. corticosteroids, azathioprine, cyclosporin, methotrexate) Steroid therapy within 4 weeks of first DC administration 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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: External Beam Radiation Therapy (RT)<br>Arm A - University of Florida - External Beam Radiation Therapy (RT) - As outlined in Intervention Description | Procedure: External Beam Radiation Therapy (RT)<br>* Day 1: Start external beam RT, 25 fractions from days 1-33 administered Monday through Friday only (no conventional external beam RT on days 6, 7, 13, 14, 20, 21, 27, or 28 Days 57-70: Surgery will occur 3-5 weeks after the final dose of external beam RT. Day 78-91: First post-operative visit Days 91-365: Clinical follow-up Beyond day 365, follow-up will be conducted using the standard of care approach applicable to these patients for the determination of disease recurrence, progression and survival.<br>|
| Experimental: External Beam RT + DC Injection<br>Arm B - Moffitt Cancer Center - External Beam RT + Autologous Dendritic Cells (DC) Injection - As outlined in Intervention Description | Procedure: External Beam Radiation Therapy (RT)<br>* Day 1: Start external beam RT, 25 fractions from days 1-33 administered Monday through Friday only (no conventional external beam RT on days 6, 7, 13, 14, 20, 21, 27, or 28 Days 57-70: Surgery will occur 3-5 weeks after the final dose of external beam RT. Day 78-91: First post-operative visit Days 91-365: Clinical follow-up Beyond day 365, follow-up will be conducted using the standard of care approach applicable to these patients for the determination of disease recurrence, progression and survival.<br>Biological: Autologous Dendritic Cells<br>* Prior to each injection on Arm B, patients may receive prophylactic doses of a first generation cephalosporin antibiotic per physician discretion. Following each DC injection, Arm B patients will assess procedure-associated pain on a scale of 0-10. The next Monday following each DC injection, the patient will be called and questioned about such procedure associated toxicities.<br>* Other names: immunotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Enhanced T Lymphocyte Immune Response Specific for Soft Tissue Sarcoma Tumor Associated Antigens(STS-TAAs) | Investigate the ability of an intensified radiation therapy (RT) regimen (namely, conventional RT with a high-dose hypofractionated boost) and Dendritic Cell (DC) administration to induce an enhanced T lymphocyte immune response specific for STS-TAAs. Criteria for immune response evaluation: Individual patients were considered as responders to TAAs if at any time point the response in IFN-γ ELISPOT assay was found higher than 30 spots per 200,000 cells or in proliferation assay higher than 3000 counts/min (CPM) AND the response in IFN-γ ELISPOT or proliferation assays to tumor cell lysates (TCL) or Ad-Surv was found more than 2SD higher than the response to corresponding control lysate or Ad-c at the same time point AND 2SD higher than the response to the same stimuli at a base line (before start of the treatment). | 11 weeks per participant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) and Adverse Events (AEs) | Evaluate the safety of intratumoral injections of DCs in combination with an intensified RT regimen patients with high-grade large STS. Toxicity assessments were performed weekly to include assessments for: constitutional symptoms, fever, fatigue; common radiation side effects; special attention was paid to DC injection and biopsy related toxicity. Only treatment related SAEs and AEs are reported for this measure. | 11 weeks per participant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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radiation, neoadjuvant, intratumoral, autologous, dendritic cells