Clinical Trials /

Immune Checkpoint Inhibitor and MR-guided SBRT for Limited Progressive Metastatic Carcinoma.

NCT04376502

Description:

This is an open label single arm phase 2 clinical trial in patients with metastatic solid malignancy of any histology who have previously experienced limited progression in at least 1 and up to 5 lesions while on immune checkpoint inhibitors monotherapy.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Immune Checkpoint Inhibitor and MR-guided SBRT for Limited Progressive Metastatic Carcinoma.
  • Official Title: Phase II Trial of Immune Checkpoint Inhibitor and Novel in Situ Radiation "Booster Shot" Tumor Vaccination in Patients With Metastatic Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: 2018-CHU-001
  • NCT ID: NCT04376502

Conditions

  • Metastatic Carcinoma

Purpose

This is an open label single arm phase 2 clinical trial in patients with metastatic solid malignancy of any histology who have previously experienced limited progression in at least 1 and up to 5 lesions while on immune checkpoint inhibitors monotherapy.

Detailed Description

      All potential subjects are required to undergo screening evaluation to determine eligibility
      within 28 days of study enrollment.

      Eligible subjects will continue the same immune checkpoint inhibitors on which they
      experienced limited progression and will also receive radiation therapy. radiation therapy
      for all subjects will consist of treating one tumor of the treating physician's preference,
      and after a 1-week interval during which immune checkpoint inhibitor is continued alone,
      radiation therapy will be given to a second and separate tumor. No additional radiation
      therapy will be delivered. immune checkpoint inhibitors will be continued until disease
      progression or unacceptable toxicity. Diagnostic imaging studies will be performed to
      determine treatment response at baseline/screening, 8 weeks after initiation of radiation
      therapy to the first lesion and every 8 weeks thereafter.

      Peripheral blood mononuclear cell composition will be evaluated at various time points within
      14 days of starting radiation therapy, on Day 8 (1 week after starting radiation therapy to
      the first lesion), Day 23 (1 week after starting radiation therapy to the second lesion), and
      8 weeks after treatment initiation.

      A total of 52 subjects will be enrolled on this trial. The expected rate of accrual is 2
      patients per month at a single institution over 26 months.
    

Trial Arms

NameTypeDescriptionInterventions
radiation therapy (RT)OtherRT for all subjects will consist of treating one tumor of the treating physician's preference (40 Gy in 5 fractions), and after a 1-week interval during which Immune checkpoint inhibitor (ICI) is continued alone, RT will be given to a second and separate tumor (30 Gy in 5 fractions).

    Eligibility Criteria

            Inclusion Criteria:
    
              1. 18 years of age at the time of study entry.
    
              2. Eastern Cooperative Oncology Group performance status of 0, 1, or 2.
    
              3. Life expectancy of .12 weeks as estimated by the treating physician.
    
              4. Metastatic carcinoma confirmed by biopsy or imaging study if biopsy is not deemed
                 feasible.
    
              5. Most recent anti-cancer therapy consists of a single ICI drug including but not
                 limited to ipilimumab, nivolumab, pembrolizumab, atezolizumab.
    
              6. Radiographic evidence of progression while on a single ICI drug in 1 and up to 5
                 lesions.
    
              7. Eligible to continue ICI during and after radiation therapy.
    
              8. 3 radiographically distinct and measurable lesions (primary and/or metastatic lesions)
                 by RECIST 1.1 criteria, with .3 lesions separated from each other by .5 cm
    
              9. Subjects must consent to all study procedures described in the protocol including
                 radiographic evaluation and blood draws.
    
             10. Immunosuppressive doses of systemic medication including steroids must be discontinued
                 at least 14 days prior to the start of radiation therapy.
    
             11. Adequate normal organ and marrow function
    
             12. Female subjects must either be of non-reproductive potential (i.e., post-menopausal by
                 history: .60 years old and no menses for .1 year without an alternative medical cause;
                 OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of
                 bilateral oophorectomy), have a negative serum pregnancy test within 14 days of study
                 enrollment, and not be breastfeeding.
    
            Exclusion Criteria:
    
              1. Any contraindication to having an MRI scan.
    
              2. Chemotherapy, biologic agent, investigational therapy, or radiation therapy given
                 within 14 days of study enrollment.
    
              3. Symptomatic or uncontrolled brain metastasis requiring treatment.
    
              4. The need for palliative radiation therapy to a non-target lesion prior to radiation
                 therapy to one of 2 target lesion on this study.
    
              5. Prior radiation therapy to any lesion that would receive radiation therapy on this
                 protocol.
    
              6. Prior radiation therapy to a lesion located within 4 cm of previously irradiated
                 structures: spinal cord that previously received >45 Gy; brachial plexus that
                 previously received >45 Gy; small/large intestine or stomach that previously received
                 >45 Gy; prior total lung V20 >30%.
    
              7. Prior radiation therapy that could lead to an unacceptably high risk of clinically
                 significant normal tissue injury due to high cumulative normal tissue dose as
                 determined by the investigator.
    
              8. History of any primary malignancy with the exception of
    
                   1. Malignancy treated with curative intent and with no known active disease for at
                      least 3 years before enrollment on this study.
    
                   2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence
                      of disease.
    
                   3. Adequately treated carcinoma in situ without evidence of disease (i.e. cervical
                      carcinoma in situ; superficial bladder cancer).
    
              9. Any unresolved toxicity (Common Terminology Criteria for Adverse Events version 5.0 >
                 grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that
                 is not reasonably expected to worsen by treatment on this study are permitted to
                 enroll on this study.
    
             10. Active or prior documented autoimmune disease within the past 2 years. Subjects with
                 vitiligo, type I diabetes mellitus, Graves disease, or psoriasis not requiring
                 systemic treatment (within the past 2 years) are not excluded.
    
             11. Subjects requiring systemic corticosteroid (>10 mg daily prednisone equivalent) or
                 other immunosuppressive medication within 14 days of study enrollment.
    
             12. Contraindication to IV contrast despite premedication for iodine allergy, which would
                 limit the ability to assess radiographic response to study treatment.
    
             13. Prior allogeneic organ transplantation.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Change in overall response rate according to RECIST 1.1 criteria
    Time Frame:6 month
    Safety Issue:
    Description:Change in overall response rate according to RECIST 1.1 criteria of non-irradiated lesions in metastatic cancer patients receiving immune checkpoint inhibitor and radiation therapy during a 6-month period.

    Secondary Outcome Measures

    Measure:Number of treatment related adverse events
    Time Frame:through study completion, an average of 1 year
    Safety Issue:
    Description:Treatment related adverse events will be tabulated and summarized by grade.
    Measure:Change in immune-related response criteria
    Time Frame:6 month
    Safety Issue:
    Description:Change in Immune-related response criteria in non-irradiated lesion(s).
    Measure:Duration of response
    Time Frame:6 month
    Safety Issue:
    Description:Duration of response from the time complete (CR) or partial response (PR) rate is first determined until the first date of documented progressive disease.
    Measure:Number of overall survival
    Time Frame:6 month
    Safety Issue:
    Description:Number of overall survival from the start of radiation therapy of the first lesion to the date of death for any cause.
    Measure:Measure the number of progression free survival
    Time Frame:6 month
    Safety Issue:
    Description:Measuring the number of progression free survival from the start of radiation therapy of the first lesion to the date of progressive disease or death for any causing.

    Details

    Phase:N/A
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Baptist Health South Florida

    Trial Keywords

    • radiation

    Last Updated

    September 18, 2020