NCT00365872

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
17

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started May 2006

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2006

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

August 17, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

August 18, 2006

Completed
5.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2012

Completed
1.6 years until next milestone

Results Posted

Study results publicly available

January 6, 2014

Completed
Last Updated

March 23, 2017

Status Verified

June 1, 2013

Enrollment Period

6.1 years

First QC Date

August 17, 2006

Results QC Date

June 25, 2013

Last Update Submit

February 20, 2017

Conditions

Soft Tissue Sarcoma

Keywords

SarcomaIntratumoral injectionDendritic cellsNeo-adjuvant treatmentImmunotherapyPheresisRadiation

Outcome Measures

Primary Outcomes (1)

  • 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-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.

    Up to 3 years

Secondary Outcomes (3)

  • Occurrence of Significant (>/= Grade 2) Toxicity

    Up to 3 years

  • Occurrence of Postoperative Wound Complications

    Up to 3 years

  • Participants With No Evidence of Disease at Follow-up

    3 years

Other Outcomes (1)

  • Number of Participants With Increase in Level of Radioactivity at Excision Per Cohort

    Up to 3 years

Study Arms (1)

EBRT + DC Injection + Resection

EXPERIMENTAL

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) InjectionsProcedure: Radiation therapyProcedure: Complete Resection - Surgery for tumor removal

Interventions

Dendritic Cell (DC) InjectionsBIOLOGICAL

* 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

EBRT + DC Injection + Resection
Radiation therapyPROCEDURE

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

EBRT + DC Injection + Resection
Complete Resection - Surgery for tumor removalPROCEDURE

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

EBRT + DC Injection + Resection

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • +2 more criteria

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Related Publications (2)

  • 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: 35135810DERIVED

  • 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.

    PMID: 26880867DERIVED

MeSH Terms

Conditions

Sarcoma

Interventions

InjectionsRadiotherapy

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft TissueNeoplasms by Histologic TypeNeoplasms

Intervention Hierarchy (Ancestors)

Drug Administration RoutesDrug TherapyTherapeutics

Results Point of Contact

Title
Scott J. Antonia, M.D., Ph.D.
Organization
H. Lee Moffitt Cancer Center and Research Institute
scott.antonia@moffitt.org
813-745-3883

Study Officials

  • Scott Antonia, M.D.

    H. Lee Moffitt Cancer Center and Research Institute

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 17, 2006

First Posted

August 18, 2006

Study Start

May 1, 2006

Primary Completion

June 1, 2012

Study Completion

June 1, 2012

Last Updated

March 23, 2017

Results First Posted

January 6, 2014

Record last verified: 2013-06

Locations

US(1)