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

  • STATUS
    Recruiting
  • End date
    Jul 30, 2025
  • participants needed
    102
  • sponsor
    Sarcoma Alliance for Research through Collaboration
Updated on 16 July 2021

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.

Description

This is a multicenter, randomized phase II trial with an initial safety run-in to test the safety and efficacy of neoadjuvant pembrolizumab with image-guided radiotherapy and adjuvant pembrolizumab compared to radiation therapy alone in patients with clinically localized extremity soft tissue sarcoma at high risk for developing metastatic disease (tumor size > 5 cm, intermediate- to high-grade; approximately 50% risk for distant disease at 2 years). Histologies will be limited to undifferentiated pleomorphic sarcoma and dedifferentiated/pleomorphic liposarcoma based on preliminary data from SARC028. Other terms for undifferentiated pleomorphic sarcoma may include, but are not limited to. pleomorphic undifferentiated sarcoma, unclassified spindle cell sarcoma, spindle cell sarcoma not otherwise specified, pleomorphic spindle cell sarcoma, pleomorphic fibroblastic sarcoma, undifferentiated high-grade pleomorphic sarcoma, pleomorphicsarcoma with prominent inflammation, pleomorphic sarcoma with giant cells, malignant fibrous histiocytoma (including storiform-pleomorphic and inflammatory subtypes), fibrosarcoma, and myxofibrosarcoma (located deep to the fascia in muscle). Radiation therapy with three cycles of pembrolizumab will be administered as neoadjuvant therapy for patients randomized to the experimental arm. These patients will also receive up to fourteen cycles of adjuvant pembrolizumab after surgical resection. Patients in the standard of care arm will receive neoadjuvant radiotherapy (50 Gy in 25 fractions) followed by surgical resection as in RTOG 0630.

Details
Condition Soft Tissue Sarcoma of the Extremity
Treatment Pembrolizumab
Clinical Study IdentifierNCT03092323
SponsorSarcoma Alliance for Research through Collaboration
Last Modified on16 July 2021

Eligibility

Yes No Not Sure

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)
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