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

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Overview

Status	Active not recruiting
Phase	Phase 2
Sponsor	Sarcoma Alliance for Research through Collaboration
Start date	July 2017
End date	September 2025
Enrollment	126 participants
Identifiers	NCT03092323, SU2C-SARC032

Conditions

Soft Tissue Sarcoma of the Extremity

Treatments

Pembrolizumab

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.

Locations

University of California Los Angeles
Los Angeles, California
Mayo Clinic- Florida
Jacksonville, Florida
University of Iowa Hospitals & Clinics
Iowa City, Iowa
University of Kansas Medical Center
Kansas City, Kansas
Johns Hopkins University
Baltimore, Maryland
Dana-Farber Cancer Institute
Boston, Massachusetts
Massachusetts General Hospital Cancer Center
Boston, Massachusetts
University of Michigan
Ann Arbor, Michigan
Washington University
Saint Louis, Missouri
Memorial Sloan Kettering Cancer Center
New York, New York
Duke University
Durham, North Carolina
The Ohio State University
Columbus, Ohio
Oregon Health & Science University
Portland, Oregon
University of Pennsylvania- Abramson Cancer Center
Philadelphia, Pennsylvania
University of Pittsburgh (UPMC Hillman Cancer Center)
Pittsburgh, Pennsylvania
Chris O'Brien Hospital
Camperdown, Australia
Princess Alexandra Hospital
Brisbane, Australia
Peter MacCallum Cancer Centre
Melbourne, Australia
McGill University Health Centre
Montreal, Canada
Fondazione IRCCS Istituto Nazionale dei Tumori
Milano, Italy

Inclusion Criteria

» 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.

Exclusion Criteria

» 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 locally recurrent sarcoma after surgery alone are eligible for enrollment if other inclusion criteria are met.

» 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

» Metastatic disease or regional lymph node involvement. Chest CT will be mandatory prior to enrollment to evaluate for the presence of metastatic disease. Pulmonary nodule(s) < 5 mm without a histological diagnosis may not be the basis for study exclusion given the lack of specificity of chest CT. If pulmonary nodule(s) measuring 6 - 10 mm are noted on chest CT but appear stable relative to prior chest imaging of at least 6 months duration or if 18FDG-PET scan indicates that the nodule(s) are unlikely to be metastatic disease, then this is permitted. Pulmonary nodules >10 mm should be considered metastatic unless proven otherwise by biopsy/resection or stable appearance for at least 6 months on imaging.

» 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.

» Active infection requiring systemic therapy

» Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

» Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent

» Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)

» Known active Hepatitis B (e.g., HBsAg reactive, confirmed by detectable viral load) or Hepatitis C (e.g., HCV RNA [qualitative] detected)

» Received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

» Diagnosis of scleroderma.

» Diagnosis of inflammatory bowel disease (Crohn's disease or Ulcerative Colitis).