Ensayos clínicos

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).