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

Soft Tissue Sarcoma Clinical Trial

Official title:

Combination of External Beam Radiation With Intratumoral Injection of Dendritic Cells as Neo-adjuvant Treatment of High-risk Soft Tissue Sarcoma Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00365872
• Other study ID #: MCC-14497
• Status: Completed
• Phase: Phase 2
• First received: August 17, 2006
• Last updated: February 10, 2014
• Start date: May 2006
• Est. completion date: June 2012

Study information

• Verified date: June 2013
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: June 2012
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Sarcoma
• Soft Tissue Sarcoma

Intervention

Biological:
• 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

Procedure:
• Radiation therapy
Radiation was delivered 5 days per week (Monday-Friday).
• Complete Resection - Surgery for tumor removal
Tumors were surgically resected 3-6 weeks after the completion of EBRT.

Locations

Country	Name	City	State
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute	Cancer Treatment Research Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Increase in Level of Radioactivity at Excision Per Cohort	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.	Up to 3 years	No
Primary	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-?) 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-? 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.	Up to 3 years	No
Secondary	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.	Up to 3 years	Yes
Secondary	Occurrence of Postoperative Wound Complications	Postoperative wound complications were defined using NCI Common Toxicity Criteria (CTC).	Up to 3 years	Yes
Secondary	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.	3 years	No