Clinical trial NCT00365872: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Soft Tissue Sarcoma
Keywords: Sarcoma
Intratumoral injection
Dendritic cells
Neo-adjuvant treatment
Immunotherapy
Pheresis
Radiation
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Cancer Treatment Research Foundation
First posted: 2006-08-18
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 3 years
Secondary outcomes:
measure: Occurrence of Significant (>/= Grade 2) Toxicity
timeFrame: Up to 3 years
measure: Occurrence of Postoperative Wound Complications
timeFrame: Up to 3 years
measure: Participants With No Evidence of Disease at Follow-up
timeFrame: 3 years
Other outcomes:
measure: Number of Participants With Increase in Level of Radioactivity at Excision Per Cohort
timeFrame: Up to 3 years
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Scott Antonia, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.