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

NCT ID: NCT00365872

Last Updated: 2017-03-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2012-06-30

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.

Conditions

Soft Tissue Sarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

EBRT + DC Injection + Resection

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

Group Type: EXPERIMENTAL

Dendritic Cell (DC) Injections

Intervention Type: BIOLOGICAL

• 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

Radiation therapy

Intervention Type: PROCEDURE

Radiation was delivered 5 days per week (Monday-Friday).

Complete Resection - Surgery for tumor removal

Intervention Type: PROCEDURE

Tumors were surgically resected 3-6 weeks after the completion of EBRT.

Interventions

Dendritic Cell (DC) Injections

• 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: BIOLOGICAL

Radiation therapy

Radiation was delivered 5 days per week (Monday-Friday).

Intervention Type: PROCEDURE

Complete Resection - Surgery for tumor removal

Tumors were surgically resected 3-6 weeks after the completion of EBRT.

Intervention Type: PROCEDURE

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cancer Treatment Research Foundation

OTHER

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Scott Antonia, M.D.

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 35135810 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26880867 (View on PubMed)

Other Identifiers

MCC-14497

Identifier Type: -

Identifier Source: org_study_id