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

NCT03092323

Description:

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.

Related Conditions:
  • Carcinoma In Situ
  • Fibrosarcoma
  • Malignant Skin Neoplasm
  • Myxofibrosarcoma
  • Pleomorphic Liposarcoma
  • Prostate Carcinoma
  • Undifferentiated Pleomorphic Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Randomized Trial of Pembrolizumab & Radiotherapy Versus Radiotherapy in High-Risk Soft Tissue Sarcoma of the Extremity
  • Official Title: SU2C-SARC032: A 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

Clinical Trial IDs

  • ORG STUDY ID: SU2C-SARC032
  • NCT ID: NCT03092323

Conditions

  • Soft Tissue Sarcoma of the Extremity

Interventions

DrugSynonymsArms
PembrolizumabKEYTRUDA®Treatment

Purpose

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.

Detailed 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.
    

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimentalNeoadjuvant pembrolizumab with concurrent radiotherapy, followed by surgical resection and adjuvant pembrolizumab.
  • Pembrolizumab
Standard of CareNo InterventionNeoadjuvant radiotherapy followed by surgical resection.

    Eligibility Criteria

            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; Alternative terms for UPS meeting inclusion criteria include but are not
                 limited to the following
    
              -  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. Imaging
                 must be performed within 45 days of Day 1 of study.
    
              -  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 three months 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) > 5 mm are
                 noted on chest CT but appear stable relative to prior chest imaging of at least 6
                 months duration, then this is permitted.
    
              -  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).
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:12 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Disease free survival
    Time Frame:2 Years
    Safety Issue:
    Description:Disease recurrence is defined as clinically diagnosed or biopsy-confirmed recurrent sarcoma at a site distant to the primary tumor, including nodal metastasis, loco-regional recurrence, and death without documented recurrence.

    Secondary Outcome Measures

    Measure:Loco-regional disease-free survival
    Time Frame:5 years
    Safety Issue:
    Description:The length of time after treatment ends without any locoregional recurrence of sarcoma.
    Measure:Distant disease free survival
    Time Frame:5 years
    Safety Issue:
    Description:The length of time after treatment ends that the patient survives without any signs or symptoms of sarcoma
    Measure:Overall survival
    Time Frame:5 years
    Safety Issue:
    Description:The length of time from the start of treatment that patients diagnosed with sarcoma are still alive.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Sarcoma Alliance for Research through Collaboration

    Last Updated