A Randomized Trial of Pembrolizumab & Radiotherapy Versus Radiotherapy in High-Risk Soft Tissue Sarcoma of the Extremity

NCT03092323 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: SU2C-SARC032
• Study Type: interventional
• Target: 126
• Locations: 4 countries
• Sites: 20

Brief Summary

This is an open-label, multi-institutional phase II randomized study comparing neoadjuvant radiotherapy followed by surgical resection to neoadjuvant pembrolizumab with concurrent radiotherapy, followed by surgical resection and adjuvant pembrolizumab. The total duration of pembrolizumab will be one year in the experimental arm.

Conditions

Soft Tissue Sarcoma of the Extremity

Outcome Measures

Primary Outcomes (1)

• Disease free survival

  Disease recurrence is defined as clinically diagnosed or biopsy-confirmed recurrent sarcoma at a site distant to the primary tumor, including nodal metastasis, loco-regional recurrence, and death without documented recurrence.

  2 Years

Secondary Outcomes (4)

• Loco-regional disease-free survival

  5 years

• Distant disease free survival

  5 years

• Overall survival

  5 years

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  5 years

Study Arms (2)

Treatment

EXPERIMENTAL

Neoadjuvant pembrolizumab with concurrent radiotherapy, followed by surgical resection and adjuvant pembrolizumab.

Drug: Pembrolizumab

Standard of Care

NO INTERVENTION

Neoadjuvant radiotherapy followed by surgical resection.

Interventions

Pembrolizumab DRUG

Pembrolizumab will be administered at 200 mg intravenously every 3 weeks for patients on the treatment arm.

Also known as: KEYTRUDA®

Treatment

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 12 years
• Histologically confirmed diagnosis of grade 2 or 3 out of 3 UPS or dedifferentiated/pleomorphic LPS of the extremity (including limb girdle, i.e. shoulder or hip) that measures greater than 5 cm in any direction as assessed by imaging
• Patients with non-melanomatous skin cancer, in situ carcinoma, or low-risk prostate cancer can be enrolled.
• ECOG Performance Status of 0 or 1
• Resectable primary tumor with no evidence of metastatic disease by imaging.
• Adequate organ function within 10 days of Day 1
• Written, voluntary informed consent
• Fertile men and women of childbearing potential must agree to use an effective method of birth control from Day 1 of study and for 120 days after last pembrolizumab administration in both sexes. Women of childbearing potential include pre-menopausal women and women within the first 2 years of the onset of menopause. Women of childbearing potential must have a negative pregnancy test ≤ 72 hours prior to Day 1 of study.

You may not qualify if:

• Prior chemotherapy, targeted small molecule therapy, or radiation therapy for current diagnosis of sarcoma
• Prior radiation therapy in excess of 20 Gy to the site of the current diagnosis of sarcoma. No overlap with prior radiation fields in excess of 20 Gy is allowed.
• Concurrent, clinically significant, active malignancies within two years of study enrollment.
• Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol
• Major surgery within four weeks prior to Day 1 of study or who have not recovered adequately from prior surgery.
• Currently receiving a study therapy or if they had an investigational agent within 4 weeks at the time of enrollment.
• Women who are pregnant or nursing/breastfeeding, or expecting to conceive or men who are expecting to 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 pembrolizumab.
• Inability to comply with protocol required procedures
• Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy by oral or IV routes within 7 days prior to the first dose of trial treatment
• Known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients
• Unresectable disease or medically inoperable
• Planned to receive neoadjuvant or adjuvant chemotherapy for current diagnosis of localized soft tissue sarcoma
• Active autoimmune disease that has required systemic treatment in the past two years (i.e. with use of disease modifying agents, systemic corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis that required systemic steroids or current pneumonitis.

Sponsors & Collaborators

• Sarcoma Alliance for Research through Collaboration: lead
• Stand Up To Cancer: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (20)

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

Mayo Clinic- Florida

Jacksonville, Florida, 32224, United States

Location

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21231, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pennsylvania- Abramson Cancer Center

Philadelphia, Pennsylvania, 19106, United States

Location

University of Pittsburgh (UPMC Hillman Cancer Center)

Pittsburgh, Pennsylvania, 15232, United States

Location

Chris O'Brien Hospital

Camperdown, New South Wales, 2050, Australia

Location

Princess Alexandra Hospital

Brisbane, Queensland, 4102, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, MI, 20133, Italy

Location

Related Publications (1)

• Mowery YM, Ballman KV, Hong AM, Schuetze SM, Wagner AJ, Monga V, Heise RS, Attia S, Choy E, Burgess MA, Bae S, Pryor DI, Van Tine BA, Tinoco G, Chmielowski B, Freeman C, Gronchi A, Meyer CF, Dickson MA, Hartner L, Davis LE, Powers BC, Moding EJ, Weinhold KJ, van de Rijn M, Brigman BE, Riedel RF, Kirsch DG. Safety and efficacy of pembrolizumab, radiation therapy, and surgery versus radiation therapy and surgery for stage III soft tissue sarcoma of the extremity (SU2C-SARC032): an open-label, randomised clinical trial. Lancet. 2024 Nov 23;404(10467):2053-2064. doi: 10.1016/S0140-6736(24)01812-9. Epub 2024 Nov 12.

  PMID: 39547252 DERIVED

MeSH Terms

Interventions

pembrolizumab

Study Officials

• David Kirsch, MD, PhD

  Princess Margaret Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2017
• First Posted: March 27, 2017
• Study Start: July 19, 2017
• Primary Completion: September 1, 2025
• Study Completion (Estimated): September 1, 2028
• Last Updated: November 18, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (15); CA (1); IT (1); AU (3)