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

Overview

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Age ≥ 12 years old.
  • 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; Alternative terms for UPS meeting inclusion criteria include but are not limited to the following:
    • 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;
    • pleomorphic sarcoma with prominent inflammation;
    • pleomorphic sarcoma with giant cells;
    • malignant fibrous histiocytoma (including storiform-pleomorphic and inflammatory subtypes);
    • fibrosarcoma;
    • myxofibrosarcoma (if located deep to the fascia in muscle).
  • For questions regarding whether histology meets inclusion criteria, please contact SARC Research project manager at the SARC Central Office.
  • 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 of study defined as:
    • Absolute Neutrophil Count (ANC) ≥ 1,500/mcL;
    • Platelets ≥ 100,000/mcL;
    • Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or erythropoietin dependency (within 7 days of assessment);
    • Serum creatinine < 1.5 X institutional upper limit of normal (ULN) OR measured or calculated creatinine clearance or GFR > 60 mL/min for subject with creatinine level > 1.5 X ULN; Note: Creatinine clearance should be calculated per institutional standard;
    • ALT (SGOT) and AST (SGPT) ≤ 2.5 X institutional ULN;
    • Serum bilirubin ≤ 1.5 X institutional ULN OR direct bilirubin < ULN for subjects with total bilirubin levels > 1.5 X ULN;
    • Albumin > 2.5 mg/dL.
  • 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 and/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).

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Steven Attia, D.O.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available
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CLS-20360314

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