Pembrolizumab and Radiation Therapy in Treating Patients With Intermediate or High-Grade Soft Tissue Sarcoma

NCT03338959 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: 9661NCI-2017-01933RG9217020
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Soft Tissue Sarcoma; Recurrent Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (1)

• Rate of Complete Tumor Necrosis

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

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

Secondary Outcomes (4)

• 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)

• Complete 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)

Study Arms (1)

Treatment (pembrolizumab, radiation therapy)

EXPERIMENTAL

Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 3 weeks for 3 months in the absence of disease progression or unacceptable toxicity. Patients also undergo radiation therapy daily for 5-6 weeks.

Biological: Pembrolizumab; Radiation: Radiation Therapy

Interventions

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, radiation therapy)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Irradiate, Irradiated, irradiation, Radiation, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation, NOS, Energy Type

Treatment (pembrolizumab, radiation therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale or \> 70% on the Karnofsky scale. Evaluation of performance status is to be performed within 7 days prior to the date of enrollment
• Absolute neutrophil count (ANC) \>= 1,500/mcL (performed within 28 days of enrollment)
• Platelets \>= 100,000/mcL (performed within 28 days of enrollment)
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L (performed within 28 days of enrollment)
• \* Criteria must be met without erythropoeiten dependency and without packed red blood cell (pRBC) transfusion within last two weeks

You may not qualify if:

• 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)
• \*NOTE: An isolated or oligo-metastatic regional recurrence may be allowed if all other criteria are met, curative attempt is being pursued
• Has known history of (non-infectious) pneumonitis that required steroids, or has current evidence of pneumonitis
• Has an active infection requiring systemic therapy
• Has known psychiatric or substance abuse disorders that would interfere with adherence to the requirements of the trial
• Is pregnant (positive urine pregnancy test within 72 hours prior to enrollment) or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. If a urine pregnancy test is positive or cannot be confirmed negative, a serum pregnancy test will be required

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Sarcoma

Interventions

pembrolizumab; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Lee Cranmer, MD, PhD, Sarcoma Program Director
• Organization: University of Washington

ldcranme@fredhutch.org

206-606-7439

Study Officials

• Lee Cranmer

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 7, 2017
• First Posted: November 9, 2017
• Study Start: March 28, 2018
• Primary Completion: June 8, 2023
• Study Completion: August 4, 2023
• Last Updated: July 23, 2024
• Results First Posted: July 23, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)