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

Primary Purpose

Soft Tissue Sarcoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Dendritic Cell (DC) Injections
Radiation therapy
Complete Resection - Surgery for tumor removal
Sponsored by
H. Lee Moffitt Cancer Center and Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Soft Tissue Sarcoma focused on measuring Sarcoma, Intratumoral injection, Dendritic cells, Neo-adjuvant treatment, Immunotherapy, Pheresis, Radiation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • H. Lee Moffitt Cancer Center & Research Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

EBRT + DC Injection + Resection

Arm Description

Single Arm: EBRT + DC Injection + Resection. Prior to the fourth DC Injection, participants were assigned to 3 cohorts as outlined in that intervention.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Occurrence of Postoperative Wound Complications
Postoperative wound complications were defined using NCI Common Toxicity Criteria (CTC).
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.

Full Information

First Posted
August 17, 2006
Last Updated
February 20, 2017
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Cancer Treatment Research Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT00365872
Brief Title
External Beam Radiation With Intratumoral Injection of Dendritic Cells As Neo-Adjuvant Treatment for Sarcoma
Official Title
Combination of External Beam Radiation With Intratumoral Injection of Dendritic Cells as Neo-adjuvant Treatment of High-risk Soft Tissue Sarcoma Patients
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Completed
Study Start Date
May 2006 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
June 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Cancer Treatment Research Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Soft Tissue Sarcoma
Keywords
Sarcoma, Intratumoral injection, Dendritic cells, Neo-adjuvant treatment, Immunotherapy, Pheresis, Radiation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
17 (Actual)

8. Arms, Groups, and Interventions

Arm Title
EBRT + DC Injection + Resection
Arm Type
Experimental
Arm Description
Single Arm: EBRT + DC Injection + Resection. Prior to the fourth DC Injection, participants were assigned to 3 cohorts as outlined in that intervention.
Intervention Type
Biological
Intervention Name(s)
Dendritic Cell (DC) Injections
Intervention Description
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
Intervention Type
Procedure
Intervention Name(s)
Radiation therapy
Intervention Description
Radiation was delivered 5 days per week (Monday-Friday).
Intervention Type
Procedure
Intervention Name(s)
Complete Resection - Surgery for tumor removal
Intervention Description
Tumors were surgically resected 3-6 weeks after the completion of EBRT.
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
Up to 3 years
Secondary Outcome Measure Information:
Title
Occurrence of Significant (>/= Grade 2) Toxicity
Description
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.
Time Frame
Up to 3 years
Title
Occurrence of Postoperative Wound Complications
Description
Postoperative wound complications were defined using NCI Common Toxicity Criteria (CTC).
Time Frame
Up to 3 years
Title
Participants With No Evidence of Disease at Follow-up
Description
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.
Time Frame
3 years
Other Pre-specified Outcome Measures:
Title
Number of Participants With Increase in Level of Radioactivity at Excision Per Cohort
Description
To identify the nodes to be excised, an injection with Indium 111 (radio active dye) labeled dendritic cells (of vaccine #4) was performed 1 to 3 days prior to surgery. Patients were evenly divided to be assigned to one of three cohorts: Cohort 1, 1 day before surgery; Cohort 2, 2 days before surgery; Cohort 3, 3 days before surgery. Vaccine #4 was labeled in order to evaluate how long dendritic cells need to travel to regional draining lymphatics. Tumor resection was not delayed by this.
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott Antonia, M.D.
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center & Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
35135810
Citation
Hong WX, Sagiv-Barfi I, Czerwinski DK, Sallets A, Levy R. Neoadjuvant Intratumoral Immunotherapy with TLR9 Activation and Anti-OX40 Antibody Eradicates Metastatic Cancer. Cancer Res. 2022 Apr 1;82(7):1396-1408. doi: 10.1158/0008-5472.CAN-21-1382.
Results Reference
derived
PubMed Identifier
26880867
Citation
Raj S, Bui MM, Springett G, Conley A, Lavilla-Alonso S, Zhao X, Chen D, Haysek R, Gonzalez R, Letson GD, Finkelstein SE, Chiappori AA, Gabrilovitch DI, Antonia SJ. Long-Term Clinical Responses of Neoadjuvant Dendritic Cell Infusions and Radiation in Soft Tissue Sarcoma. Sarcoma. 2015;2015:614736. doi: 10.1155/2015/614736. Epub 2015 Dec 31.
Results Reference
derived

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

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