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

NCT01347034 | Completed Phase 2 Results

• 1 other identifier: MCC-16441
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

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.

Conditions

Soft Tissue Sarcoma

Keywords

radiation; neoadjuvant; intratumoral; autologous; dendritic cells

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

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

  11 weeks per participant

Study Arms (2)

External Beam Radiation Therapy (RT)

ACTIVE COMPARATOR

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

Procedure: External Beam Radiation Therapy (RT)

External Beam RT + DC Injection

EXPERIMENTAL

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

Procedure: External Beam Radiation Therapy (RT); Biological: Autologous Dendritic Cells

Interventions

External Beam Radiation Therapy (RT) PROCEDURE

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.

External Beam RT + DC Injection; External Beam Radiation Therapy (RT)

Autologous Dendritic Cells BIOLOGICAL

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.

Also known as: immunotherapy

External Beam RT + DC Injection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• University of Florida: collaborator

Study Sites (3)

Shands University of Florida Department of Radiation Oncology

Gainesville, Florida, 32608, United States

Location

Shands Jacksonville Department of Radiation Oncology

Jacksonville, Florida, 32206, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Related Publications (1)

• 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.

  PMID: 35135810 DERIVED

MeSH Terms

Conditions

Sarcoma

Interventions

Immunotherapy

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics

Limitations and Caveats

Investigators planned to accrue 21 patients in each arm for a total of 42 participants.

Results Point of Contact

• Title: Alberto Chiappori, M.D.
• Organization: H. Lee Moffitt Cancer Center and Research Institute

alberto.chiappori@moffitt.org

813-745-3050

Study Officials

• Alberto Chiappori, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

• Daniel Indelicato, M.D.

  University of Florida, Shands Jacksonville

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2011
• First Posted: May 4, 2011
• Study Start: January 1, 2011
• Primary Completion: August 1, 2013
• Study Completion: April 1, 2016
• Last Updated: May 23, 2016
• Results First Posted: August 8, 2014

Record last verified: 2016-04

Locations

US (3)