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

Study Overview
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Brief Summary
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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 was to determine if an injection of the patient's own immune related white blood cells into their tumor would strengthen the immune system to fight against their cancer.

Detailed Description
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Patients were treated with external beam radiation therapy (EBRT) combined with experimental intratumoral injection of dendritic cell (DC). Patients received 5,040 centigray (cGy) EBRT in 28 equal fractions. Radiation was delivered 5 days per week (Monday-Friday). DCs (10^7 cells) were injected intratumorally three times on the second, third, and fourth Friday during the course of radiation. One additional DC injection was given several days before surgery to assess DC migration. Tumors were surgically resected 3-6 weeks after the completion of EBRT.

Official Title
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Combination of External Beam Radiation With Intratumoral Injection of Dendritic Cells as Neo-adjuvant Treatment of High-risk Soft Tissue Sarcoma Patients

Conditions
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Soft Tissue Sarcoma

Intervention / Treatment
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* Biological: Dendritic Cell (DC) Injections
* Procedure: Radiation therapy
* Procedure: Complete Resection - Surgery for tumor removal


Participation Criteria
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Eligibility Criteria
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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.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EBRT + DC Injection + Resection<br>Single Arm: EBRT + DC Injection + Resection. Prior to the fourth DC Injection, participants were assigned to 3 cohorts as outlined in that intervention. | Biological: Dendritic Cell (DC) Injections<br>* DCs (10^7 cells) were injected intratumorally three times on the second, third, and fourth Friday during the course of radiation. One additional DC injection was given before surgery to assess DC migration Patients were 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<br>Procedure: Radiation therapy<br>* Radiation was delivered 5 days per week (Monday-Friday).<br>Procedure: Complete Resection - Surgery for tumor removal<br>* Tumors were surgically resected 3-6 weeks after the completion of EBRT.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Immune responses in patients treated with EBRT and DCs: Transient immune response = response detected at only one time point; Robust immune response = response detected at least at two time points. An individual patient was considered a responder to tumor cell lysates (TCL) or survivin if at any time point the response in the interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assay was higher than 30 spots per 2 X 10^5 cells and in the proliferation assay higher than 3,000 counts per minute (CPM) and the response in IFN-γ ELISPOT or proliferation assays to TCL or Ad-surv was more than 2 standard deviations (SD) higher than the response to the corresponding control lysate or Ad-c at the same time point and 2 SD higher than the response to the same stimuli before start of the treatment. | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Significant (>/= Grade 2) Toxicity | Toxicity assessment during combination external beam radiation therapy (EBRT)/DC neoadjuvant treatment. Toxicity was assessed according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria. | Up to 3 years | 
| Occurrence of Postoperative Wound Complications | Postoperative wound complications were defined using NCI Common Toxicity Criteria (CTC). | Up to 3 years | 
| Participants With No Evidence of Disease at Follow-up | Participants who had no evidence of the disease for at least one year after the start of the treatment (time of follow-up); for at least 2 years, and for at least 3 years. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sarcoma, Intratumoral injection, Dendritic cells, Neo-adjuvant treatment, Immunotherapy, Pheresis, Radiation