Clinical Trials /

Immunotherapy + Radiation in Resectable Soft Tissue Sarcoma

NCT03463408

Description:

Immunotherapy + Radiation in Resectable Soft Tissue Sarcoma

Related Conditions:
  • Soft Tissue Sarcoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Immunotherapy + Radiation in Resectable Soft Tissue Sarcoma
  • Official Title: Pilot Study of Neoadjuvant Dual Checkpoint Blockade With Concurrent Radiation in Resectable Soft Tissue Sarcoma

Clinical Trial IDs

  • ORG STUDY ID: USAR17101
  • NCT ID: NCT03463408

Conditions

  • Sarcoma

Interventions

DrugSynonymsArms
nivolumabImmunotherapy arm
ipilimumabImmunotherapy arm

Purpose

Immunotherapy + Radiation in Resectable Soft Tissue Sarcoma

Detailed Description

      A single institution two cohort, open label, non-randomized study of neoadjuvant nivolumab
      and ipilimumab with concurrent radiation followed by surgical resection.

      Cohort A will comprise adult soft tissue sarcoma patents who consent to and receive
      ipilimumab + nivolumab concurrently with standard of care radiation. Ipilimumab will be given
      at a dose of 1 mg/kg every 6 weeks (total two doses) and nivolumab given as a flat dose of
      240 mg every 2 weeks (total four doses).

      Cohort B will comprise patients eligible for the trial who do not wish to receive
      immunotherapy but consent to the same blood draws, surveys, and specimen analysis as Cohort
      A. Cohort B will serve as a non-randomized but pragmatic and clinically relevant control
      group.

      Peripheral blood will be collected on day 1 pre-treatment, day 14, day 42, immediately prior
      to surgery, and at 3 month follow up. Peripheral blood will be sent for multidimensional flow
      analysis of changes in immune cell composition and markers of proliferation. Serum samples
      will be obtained before starting treatment and after surgery. Samples from select subjects
      whose resected tumors show significant response and whose tumors showed minimal response will
      be sent to Serametrix for serum profiling to detect antibody response to a panel of
      tumor-specific antigens.

      Standard surgical resection will be done 2 to 4 weeks after completion of radiotherapy.
      Accrual is expected to occur over 2 years. Follow up data will be collected for up to 3 years
      post-treatment.
    

Trial Arms

NameTypeDescriptionInterventions
Immunotherapy armExperimentalCohort A will comprise adult soft tissue sarcoma patents who consent to and receive ipilimumab + nivolumab concurrently with standard of care radiation. Ipilimumab will be given at a dose of 1 mg/kg every 6 weeks (total two doses) and nivolumab given as a flat dose of 240 mg every 2 weeks (total four doses). Standard surgical resection will be done 2 to 4 weeks after completion of radiotherapy. Accrual is expected to occur over 2 years. Follow up data will be collected for up to 3 years post-treatment.
  • nivolumab
  • ipilimumab
no immunotherapy armNo InterventionCohort B will comprise patients eligible for the trial who do not wish to receive immunotherapy but consent to the same blood draws, surveys, and specimen analysis as Cohort A. Cohort B will serve as a non-randomized but pragmatic and clinically relevant control group. Standard surgical resection will be done 2 to 4 weeks after completion of radiotherapy. Accrual is expected to occur over 2 years. Follow up data will be collected for up to 3 years post-treatment.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Diagnosed with biopsy-proven soft-tissue sarcoma with confirmatory pathology review at
                 University of Rochester Medical Center (URMC)
    
              -  18 years or older.
    
              -  Able to provide informed consent.
    
              -  Resectable disease per surgical evaluation.
    
              -  Neoadjuvant/preoperative radiotherapy has been recommended
    
              -  Intermediate to high grade sarcoma on biopsy, tumor > 5 cm in size by imaging
    
              -  Willing to have blood draws for flow cytometry and Serametrix analysis.
    
              -  Willing to receive neoadjuvant radiation therapy and subsequent surgical resection.
    
              -  Patients with known human immunodeficiency virus (HIV) are eligible if the lymphocytes
                 > 350 CD4+ cells and no detectable viral load.
    
              -  Women of childbearing potential (defined as any woman, who 1) has not undergone tubal
                 ligation, a hysterectomy or bilateral oophorectomy; or 2) has not been naturally
                 postmenopausal for at least 24 consecutive months or has had menses at any time in the
                 preceding 24 consecutive months):
    
                   -  Must not be pregnant or nursing
    
                   -  Must have a negative pregnancy test done within 7 days prior to registration as
                      well as within 72 hrs. prior to receiving first dose of study medication
    
                   -  Women of childbearing potential must use at least two other accepted and
                      highly-effective methods of contraception and/or agree to abstain from sexual
                      intercourse for at least 5 months after the last dose of nivolumab and/or
                      ipilimumab.
    
                   -  Should a woman become pregnant or suspect she is pregnant while she is
                      participating in this study, she should inform her treating physician
                      immediately.
    
              -  Sexually active males must use at least two other accepted and highly-effective
                 methods of contraception and/or agree to abstain from sexual intercourse for at least
                 7 months after the last dose of nivolumab and/or ipilimumab
    
              -  Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
    
            Exclusion Criteria:
    
              -  Gastrointestinal stromal tumor, dermatofibrosarcoma protuberans, rhabdomyosarcoma,
                 Ewing's sarcoma, low-grade sarcomas, osteosarcoma subtypes
    
              -  History of radiation to the affected area
    
              -  Evidence of metastatic disease prior to treatment
    
              -  Any history of prior therapy with ipilimumab or nivolumab, or any agent targeting
                 PD-1, PD-L1 or CTLA-4.
    
              -  History of any the following:
    
                   -  Active known or suspected autoimmune disease
    
                   -  Active autoimmune colitis
    
                   -  Autoimmune pan hypopituitarism
    
                   -  Autoimmune adrenal insufficiency
    
                   -  Known active hepatitis B or C
    
                   -  Known active pulmonary disease with hypoxia defined as:
    
              -  Oxygen saturation < 85% on room air or
    
              -  Oxygen saturation < 88% despite supplemental oxygen
    
              -  No systemic treatment with either corticosteroids (> 10 mg daily prednisone
                 equivalents) or other immunosuppressive medications within 14 days of registration.
    
              -  Second active malignancy, not including localized basal cell skin cancer, squamous
                 cell skin cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the
                 breast; patients with a history of other malignancies are eligible if they have been
                 continuously disease-free for > 3 years prior to the time of registration.
    
              -  Absolute neutrophil count (ANC) <= 1,500/mm^3
    
              -  Platelet count <= 100,000/mm^3
    
              -  AST (Aspartate Aminotransferase) or ALT (Alanine Aminotransferase) => 2 x upper limit
                 of normal (ULN)
    
              -  Thyroid stimulating hormone (TSH) outside of normal limits; supplementation is
                 acceptable to achieve a TSH within normal limits; in patients with abnormal TSH if
                 free T4 is normal and patient is clinically euthyroid, patient is eligible.
    
              -  Life expectancy under 5 years.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Adverse Event evaluation
    Time Frame:2 years
    Safety Issue:
    Description:Evaluate safety through assessment of adverse events throughout the course of treatment

    Details

    Phase:Early Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:University of Rochester

    Trial Keywords

    • Sarcoma

    Last Updated