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A Trial for Treatment of Cancer Patients With Multiple Brain Metastases Undergoing Whole-Brain Radiotherapy

NCT03608020

Description:

This protocol is for a lead-in safety study of 5 patients followed by a randomized Phase 2 clinical trial of BMX-001, a new class of pharmaceutical, in 64 patients with multiple brain metastases (MBM) undergoing whole brain radiation therapy (WBRT). Preliminary studies have demonstrated that BMX-001 provides protection of normal tissues from radiation-induced injury and augments tumor growth inhibition.

Related Conditions:
  • Breast Carcinoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Trial for Treatment of Cancer Patients With Multiple Brain Metastases Undergoing Whole-Brain Radiotherapy
  • Official Title: A Safety Lead-In/Randomized Phase 2 Study of BMX-001 as a Therapeutic Agent for Treatment of Cancer Patients With Multiple Brain Metastases Undergoing Whole-Brain Radiotherapy

Clinical Trial IDs

  • ORG STUDY ID: BMX-MBM-001
  • SECONDARY ID: 1R44CA228694-01
  • NCT ID: NCT03608020

Conditions

  • Multiple Brain Metastases

Interventions

DrugSynonymsArms
BMX-001Whole Brain Radiation TherapyWBRT + BMX-001

Purpose

This protocol is for a lead-in safety study of 5 patients followed by a randomized Phase 2 clinical trial of BMX-001, a new class of pharmaceutical, in 64 patients with multiple brain metastases (MBM) undergoing whole brain radiation therapy (WBRT). Preliminary studies have demonstrated that BMX-001 provides protection of normal tissues from radiation-induced injury and augments tumor growth inhibition.

Detailed Description

      This protocol is for a Phase 1 safety lead-in clinical trial of BMX-001 in combination with
      WBRT in 5 patients with MBM. Demonstrating safety of the selected MTD of BMX-001 in patients
      with MBM undergoing standard protocol WBRT will be the "go/no-go" criteria for proceeding to
      Phase 2.

      Phase 2 is a randomized open-label Phase 2 clinical trial of 64 patients with MBM, half
      receiving BMX-001 in combination with WBRT and half receiving WBRT alone.

      Subjects are treated with BMX-001 for a total of 19 days, during which time they receive
      radiation therapy. Following completion of radiation therapy, subjects will be followed for
      an additional one year.
    

Trial Arms

NameTypeDescriptionInterventions
WBRT + BMX-001Active ComparatorWhole brain radiation therapy in combination with BMX-001 (subcutaneous injection of 28 mg loading dose, followed by subsequent 14 mg twice per week for 2 weeks).
  • BMX-001
Whole Brain Radiation TherapyNo InterventionWhole brain radiation therapy per standard of care.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Subjects must have histologically confirmed diagnosis of a non-small cell lung cancer,
                 breast cancer, melanoma or renal cell cancer primary
    
              -  Subjects must have >10 contrast-enhancing lesions, never previously treated with SRS
                 and/or surgical resection, on a contrast-enhanced T1-weighted brain MRI performed
                 within two weeks of enrollment, with at least one lesion >0.5cm in greatest dimension
    
              -  Physical examination by a radiation oncologist or medical oncologist within 14 days of
                 the start of WBRT
    
              -  Plan to be treated with WBRT to a dose of 30 Gy in 10 fractions
    
              -  Age * 18 years
    
              -  Karnofsky Performance Status (KPS) ≥ 70
    
              -  Hemoglobin ≥ 9.0 g/dl, ANC ≥ 1,500 cells/*l, platelets ≥ 125,000 cells/*l
    
              -  Serum creatinine ≤ 1.5 mg/dl, serum SGOT and bilirubin ≤ 1.5 times upper limit of
                 normal
    
              -  Signed informed consent approved by the Institutional Review Board
    
              -  If sexually active, patients must agree to use appropriate contraceptive measures for
                 the duration of the study and for 6 months afterwards as stated in the informed
                 consent
    
              -  Able to provide study specific informed consent
    
              -  Willing to follow study procedures, complete QOL questionnaires and neurocognitive
                 testing as described in the protocol
    
              -  Negative serum pregnancy test for women of child bearing potential within 48 hours of
                 first dose of BMX
    
            Exclusion Criteria:
    
              -  Active infection requiring IV antibiotics 7 days before enrollment
    
              -  Hypertension requiring 3 or more anti-hypertensive medications to control
    
              -  Requirement for concurrent treatment with nitrates or other drugs that may, in the
                 judgment of the treating investigator, create a risk for a precipitous decrease in
                 blood pressure
    
              -  History of syncope within the last 6 months
    
              -  Subjects receiving prohibited medications listed in Section 6.4.2 of this protocol are
                 not eligible. Subjects who can safely stop taking a prohibited medication at least 7
                 days prior to the first dose of BMX may participate at the discretion of the treating
                 physician.
    
              -  Pregnancy or women of childbearing potential and men who are sexually active and not
                 willing/able to use medically acceptable forms of contraception; this exclusion is
                 necessary because the treatment involved in this study may be significantly
                 teratogenic
    
              -  Women who are breast feeding
    
              -  Known hypersensitivity to compounds of similar chemical composition to BMX-001
    
              -  Prior surgical resection for brain metastases and/or stereotactic radiosurgery for up
                 to 5 brain metastases in total are permitted if performed at least 1 month prior to
                 planned WBRT under this protocol.
    
              -  Prior whole brain radiation therapy
    
              -  Patients with diffuse leptomeningeal disease (carcinomatous meningitis)
    
              -  A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a
                 QTc interval >480 milliseconds (ms) (CTCAE grade 1)
    
              -  A history of additional risk factors for TdP (e.g., congestive heart failure,
                 hypokalemia, known family history of Long QT Syndrome)
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Assess safety and tolerability of WBRT + BMX-001 through proportion of patients who experience grade 4 or 5 study drug related adverse events.
    Time Frame:1 year
    Safety Issue:
    Description:AEs will be assessed according to the CTCAE version 5.0. If CTCAE grading does not exist for an AE, the severity of the AE will be graded as mild (1), moderate (2), severe (3), life-threatening (4), or fatal (5). Initially 5 patients will be accrued and treated with WBRT + BMX-001 as a lead-in safety phase. Enrollment to the randomized phase of the study will not proceed if patients in the safety lead-in phase experience the following: Two or more patients are unable to complete radiation therapy (RT) due to toxicity related to BMX-001 (alone or in combination with RT. Two or more patients experience delay in starting RT due to toxicity related to BMX-001 (alone or in combination with RT). If any patient experiences a grade 4 or 5 BMX-001-related adverse event within Arm A (WBRT + BMX-001), accrual will be suspended and the experience of the patient will be carefully reviewed by the clinical team and the study's DSMB.

    Secondary Outcome Measures

    Measure:Compare survival in WBRT + BMX-001 vs WBRT alone
    Time Frame:1 Year
    Safety Issue:
    Description:Survival
    Measure:Compare local recurrence rate in WBRT + BMX-001 vs WBRT alone
    Time Frame:1 Year
    Safety Issue:
    Description:Median time to local brain failure or progression
    Measure:Compare distant brain failure rate in WBRT + BMX-001 vs WBRT alone
    Time Frame:1 Year
    Safety Issue:
    Description:Median time to distant brain failure
    Measure:Compare rate of neurologic death in WBRT + BMX-001 vs WBRT alone
    Time Frame:1 Year
    Safety Issue:
    Description:Proportion of patients who are dead within 1 year of initiation of WBRT due to neurologic disease and/or disseminated leptomeningeal carcinomatosis.

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:BioMimetix JV, LLC

    Last Updated

    November 5, 2019