A Pilot Study of Pembrolizumab and Neoadjuvant Radiation for Large, High-Risk Soft Tissue Sarcomas

Fred Hutchinson Cancer Center1 site in 1 country27 target enrollmentMarch 28, 2018

ConditionsSoft Tissue Sarcoma Recurrent Soft Tissue Sarcoma

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Soft Tissue Sarcoma
Sponsor: Fred Hutchinson Cancer Center
Enrollment: 27
Locations: 1
Primary Endpoint: Rate of Complete Tumor Necrosis
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This phase I/II trial studies pembrolizumab and radiation therapy in treating patients with intermediate or high-grade soft tissue sarcoma. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving pembrolizumab and radiation therapy may work better in treating patients with soft tissue sarcoma.

Detailed Description

OUTLINE: Patients receive pembrolizumab intravenously (IV) per institutional standard at the Seattle Cancer Care Alliance as an outpatient therapy. Cycles repeat every 3 weeks, up to a maximum of three doses, for 3 months in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy daily for 5-6 weeks beginning on Day 1 of Week 2. After completion of study treatment, patients are followed up at 30 days after last dose, 90 days after last dose, 30 days after post-operative visit (wound care follow-up), and then every 12 weeks for up to 1 year, then every 6 months up to 5 years.

Registry

clinicaltrials.gov

Start Date

March 28, 2018

End Date

August 4, 2023

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Fred Hutchinson Cancer Center

Responsible Party

Principal Investigator

Lee Cranmer

Professor

Fred Hutchinson Cancer Center

Eligibility Criteria

Inclusion Criteria

•Be willing and able to provide written informed consent for the trial
•Be ≥18 years of age on day of signing informed consent documents
•Have measurable disease based on RECIST 1.1
•Have newly diagnosed disease or localized recurrent or oligometastatic lesions that are candidates for radiation
•NOTE: Subjects may not have any prior systemic therapy or radiation for this sarcoma. They may have received systemic therapy and/or radiation for a different cancer
•NOTE: Oligometastatic disease will be defined as 3 or fewer detectable lesions with plans to radiate all detectable disease with conventionally fractionated radiation prior to resection
•Have an intermediate- or high-grade soft tissue sarcoma at the discretion of the reviewing Sarcoma pathologist
•The tumor must be at least 3 cm in maximum dimension for intermediate-grade tumors, or 1.5 cm in maximum dimension for high-grade tumors
•Have plans to undergo neo-adjuvant radiation and surgery with curative intent. A minimum of 45 Gy is necessary, planned to be administered over a minimum of 25 fractions
•Be willing to provide tissue from a newly obtained core incisional or excisional biopsy of a tumor lesion. Archival tissue from a recent clinical or research biopsy (within 90 days prior to Week 1 treatment) may be used in place of a fresh tissue biopsy

Exclusion Criteria

•Has had prior radiation to affected area
•Has one of the following sarcoma subtypes where neoadjuvant chemotherapy is established as practice at our institution: extra-skeletal Ewing's sarcoma, embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma
•\* NOTE: Pleomorphic rhabdomyosarcoma is allowed. Bone sarcomas including osteosarcoma, Ewing's sarcoma and chondrosarcoma are not allowed. Extra-skeletal Osteosarcoma is considered a soft tissue sarcoma and is allowed.
•Has a diagnosis of immunodeficiency or has an active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid)
•Is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
•Has a known history of active TB (Bacillus tuberculosis)
•Hypersensitivity (\>= grade 3) to pembrolizumab and/or any of its excipients
•Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
•\* NOTE: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in-situ cancers
•Has current or a history of any distant metastatic disease (including brain)

Outcomes

Primary Outcomes

Rate of Complete Tumor Necrosis

Time Frame: From baseline through wound care follow-up visit (up to 8 months)

Necrosis greater than or equal to 90% at pathologic assessment at time of surgery

Secondary Outcomes

Complete Response Rate(From baseline through wound care follow-up visit (up to 8 months))
Incidence of Adverse Events(Through the wound care follow-up visit (up to 8 months))
Partial Response Rate(From baseline through wound care follow-up visit (up to 8 months))
Overall Response Rate(From baseline through wound care follow-up visit (up to 8 months))