Back to results

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

Primary Purpose

Soft Tissue Sarcoma

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

External Beam Radiation Therapy (RT)

Autologous Dendritic Cells

About this trial

This is an interventional treatment trial for Soft Tissue Sarcoma focused on measuring radiation, neoadjuvant, intratumoral, autologous, dendritic cells

Eligibility Criteria

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

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).

Sites / Locations

Shands University of Florida Department of Radiation Oncology
Shands Jacksonville Department of Radiation Oncology
H. Lee Moffitt Cancer Center and Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

External Beam Radiation Therapy (RT)

External Beam RT + DC Injection

Arm Description

Arm A - University of Florida - External Beam Radiation Therapy (RT) - As outlined in Intervention Description

Arm B - Moffitt Cancer Center - External Beam RT + Autologous Dendritic Cells (DC) Injection - As outlined in Intervention Description

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT01347034

First Posted

May 2, 2011

Last Updated

April 21, 2016

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

University of Florida

1. Study Identification

Unique Protocol Identification Number

NCT01347034

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2016

Overall Recruitment Status

Completed

Study Start Date

January 2011 (undefined)

Primary Completion Date

August 2013 (Actual)

Study Completion Date

April 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Collaborators

University of Florida

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Soft Tissue Sarcoma

Keywords

radiation, neoadjuvant, intratumoral, autologous, dendritic cells

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

External Beam Radiation Therapy (RT)

Arm Type

Active Comparator

Arm Description

Arm A - University of Florida - External Beam Radiation Therapy (RT) - As outlined in Intervention Description

Arm Title

External Beam RT + DC Injection

Arm Type

Experimental

Arm Description

Arm B - Moffitt Cancer Center - External Beam RT + Autologous Dendritic Cells (DC) Injection - As outlined in Intervention Description

Intervention Type

Procedure

Intervention Name(s)

External Beam Radiation Therapy (RT)

Intervention Description

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.

Intervention Type

Biological

Intervention Name(s)

Autologous Dendritic Cells

Other Intervention Name(s)

immunotherapy

Intervention Description

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.

Primary Outcome Measure Information:

Title

Number of Participants With Enhanced T Lymphocyte Immune Response Specific for Soft Tissue Sarcoma Tumor Associated Antigens(STS-TAAs)

Description

Time Frame

11 weeks per participant

Secondary Outcome Measure Information:

Title

Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) and Adverse Events (AEs)

Description

Time Frame

11 weeks per participant

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Alberto Chiappori, M.D.

Organizational Affiliation

H. Lee Moffitt Cancer Center and Research Institute

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Daniel Indelicato, M.D.

Organizational Affiliation

University of Florida, Shands Jacksonville

Official's Role

Principal Investigator

Facility Information:

Facility Name

Shands University of Florida Department of Radiation Oncology

City

Gainesville

State/Province

Florida

ZIP/Postal Code

32608

Country

United States

Facility Name

Shands Jacksonville Department of Radiation Oncology

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32206

Country

United States

Facility Name

H. Lee Moffitt Cancer Center and 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

Learn more about this trial

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

We'll reach out to this number within 24 hrs