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

This study has been completed.
Sponsor:
Collaborator:
Cancer Treatment Research Foundation
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00365872
First received: August 17, 2006
Last updated: February 10, 2014
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Soft Tissue Sarcoma
Biological: Dendritic Cell (DC) Injections
Procedure: Radiation therapy
Procedure: Complete Resection - Surgery for tumor removal
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Combination of External Beam Radiation With Intratumoral Injection of Dendritic Cells as Neo-adjuvant Treatment of High-risk Soft Tissue Sarcoma Patients

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Overall Response Rate (ORR) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    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-γ) 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-γ 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.


Secondary Outcome Measures:
  • Occurrence of Significant (>/= Grade 2) Toxicity [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    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.

  • Occurrence of Postoperative Wound Complications [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
    Postoperative wound complications were defined using NCI Common Toxicity Criteria (CTC).

  • Participants With No Evidence of Disease at Follow-up [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Number of Participants With Increase in Level of Radioactivity at Excision Per Cohort [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    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.


Enrollment: 17
Study Start Date: May 2006
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
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).
Procedure: Complete Resection - Surgery for tumor removal
Tumors were surgically resected 3-6 weeks after the completion of EBRT.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00365872

Locations
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Cancer Treatment Research Foundation
Investigators
Principal Investigator: Scott Antonia, M.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00365872     History of Changes
Other Study ID Numbers: MCC-14497
Study First Received: August 17, 2006
Results First Received: June 25, 2013
Last Updated: February 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Sarcoma
Intratumoral injection
Dendritic cells
Neo-adjuvant treatment
Immunotherapy
Pheresis
Radiation

Additional relevant MeSH terms:
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on September 22, 2014