SU2C-SARC032: This Phase II trial is trying to determine whether using immunotherapy and radiotherapy for the treatment of localised, high-risk soft tissue sarcoma is more effective than giving radiotherapy aloneA Phase II Randomized Controlled Trial of Neoadjuvant Pembrolizumab With Radiotherapy and Adjuvant Pembrolizumab in Patients With High-Risk, Localized Soft Tissue Sarcoma of the Extremity

Exclusion

• 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).