Clinical Trials /

Safety and Efficacy Study of Trans Sodium Crocetinate (TSC) in Newly Diagnosed Glioblastoma (GBM) Biopsy-Only Subjects

NCT03393000

Description:

Open-label, randomized, controlled, phase 3 safety and efficacy registration trial. Subjects will be randomized at baseline to the standard of care for first-line treatment of glioblastoma plus Trans Sodium Crocetinate (TSC) or the standard of care. The standard of care for GBM will consist of temozolomide plus radiation therapy for 6 weeks followed by 28 days of rest followed by 6 cycles of post-radiation temozolomide treatment.

Related Conditions:
  • Glioblastoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy Study of Trans Sodium Crocetinate (TSC) in Newly Diagnosed Glioblastoma (GBM) Biopsy-Only Subjects
  • Official Title: Open-label, Randomized, Controlled, Phase 3 Safety and Efficacy Study of Trans Sodium Crocetinate With Radiation Therapy and Temozolomide in Newly Diagnosed Glioblastoma (GBM) Biopsy-Only Subjects

Clinical Trial IDs

  • ORG STUDY ID: 100-206
  • NCT ID: NCT03393000

Conditions

  • Glioblastoma

Interventions

DrugSynonymsArms
Trans Sodium Crocetinate plus SOCTrans Sodium Crocetinate (TSC) plus Standard of CareTrans Sodium Crocetinate plus SOC

Purpose

Open-label, randomized, controlled, phase 3 safety and efficacy registration trial. Subjects will be randomized at baseline to the standard of care for first-line treatment of glioblastoma plus Trans Sodium Crocetinate (TSC) or the standard of care. The standard of care for GBM will consist of temozolomide plus radiation therapy for 6 weeks followed by 28 days of rest followed by 6 cycles of post-radiation temozolomide treatment.

Detailed Description

      During the radiation treatment period subjects will receive:

        1. Focal radiation delivered as 60 Gray/30 fractions scheduled at 2 Gray/day for 5 days
           each week (Monday through Friday) for 6 weeks.

        2. Temozolomide 75mg/m2 orally once daily (usually administered the night preceding each
           radiation session) starting the evening before the first radiation session over a period
           of 42 calendar days with a maximum of 49 days.

        3. TSC 0.25 mg/kg IV for 3 days each week (Monday, Wednesday, Friday) administered between
           45 to 60 minutes prior to each radiation session.

      Pneumocystis carinii pneumonia (PCP) prophylaxis is required during Temozolomide + radiation
      administration, regardless of lymphocyte count and is to continue until recovery of
      lymphocyte count to less than or equal to Grade 1.

      During the 28-day rest period all subjects will receive no treatment.

      During the post-radiation 6-cycle temozolomide treatment period subjects will receive:

      All subjects will receive: 28-day oral temozolomide (150 mg/m2 first cycle and 200 mg/m2 all
      subsequent cycles as tolerated) administered on Day 1-5 (Monday through Friday) of each
      28-day cycle.

      Controls: Will receive oral temozolomide at night at home per the standard of care.

      Subjects randomized to TSC: Will receive TSC 1.5 mg/kg (or the dose recommended by the Data
      Safety Monitoring Board) 1.5 to 2 hours before their temozolomide dose during the daytime for
      3 days during the first week of each 28-day cycle (Days 1, 3, 5: Monday, Wednesday, Friday).
      The Tuesday, Thursday doses will be given at night at home. Long-acting antiemetics may be
      administered prior to daytime temozolomide dosing on Days 1, 3, 5.

      In accordance with the FDA directive of August 22, 2017 the safety, tolerability and
      pharmacokinetics of TSC at doses between 0.25 mg/kg and up to 1.5 mg/kg in combination with
      concomitant temozolomide will be assessed via a dose escalation run-in prior to initiating
      the randomized trial.

      The first eight (8) subjects enrolled in the 100-206 trial will be assigned (not randomized
      between treatments) at Baseline to undergo radiation plus temozolomide plus TSC treatment
      (0.25 mg/kg) for 6 weekly cycles followed by 4 weeks of rest in standard fashion. At the Week
      10 clinic visit the same eight (8) subjects will be assigned to treatment with 2 subjects
      each assigned to TSC at doses of 0.25, 0.50, 1.0 and 1.5 mg/kg.

      The first eight (8) subjects will be studied in parallel and all for two full 28-day cycles
      with inclusion of appropriate blood sampling collection for TSC and temozolomide
      pharmacokinetics.

      The Data Safety Monitoring Board will examine the resultant safety data after 2 full cycles
      (Weeks 11 through 18 of post-radiation temozolomide treatment period; Days 1 to 56).

      The eight (8) subjects that are a part of the dose-escalation run-in will continue at their
      assigned TSC dose (0.25, 0.5, 1.0, 1.5 mg/kg) for the Week 19 TSC dosing period.

      The Data Safety Monitoring Board will recommend an acceptable TSC dose, if different than 1.5
      mg/kg, for the post-radiation temozolomide treatment period prior to the Week 23 TSC dosing
      period for the eight (8) subjects that are a part of the dose-escalation run-in.

      Thereafter, subjects will enter the 100-206 trial and be randomized at Baseline between TSC
      plus standard of care or the standard of care.
    

Trial Arms

NameTypeDescriptionInterventions
Trans Sodium Crocetinate plus SOCExperimentalTrans Sodium Crocetinate plus the Standard of Care (SOC): SOC composed of radiation and temozolomide for 6 weeks followed by 4 weeks of rest followed by six (6) 28-day cycles of temozolomide
  • Trans Sodium Crocetinate plus SOC
Standard of Care (SOC)Active ComparatorStandard of Care (SOC): SOC composed of radiation and temozolomide for 6 weeks followed by 4 weeks of rest followed by six (6) 28-day cycles of temozolomide

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Male or female subjects who are at least 18 to 70 years of age
    
              2. Have histologically confirmed GBM
    
              3. The only surgical consideration is biopsy. Subjects who had gross total resection,
                 partial resection and/or debulking are excluded.
    
              4. Measurable (>10mm x 10mm) contrast enhancing disease.
    
              5. Limited disturbance of tumor during biopsy.
    
              6. Surgical and pathology reports that document surgery was limited to biopsy and
                 histologic confirmation.
    
              7. Life expectancy of at least 3 months.
    
              8. Subjects must have a Karnofsky score (KPS) of ≥ 60 at Screening.
    
              9. Glucocorticoid therapy allowed.
    
             10. Tumor Treatment Field (TT Fields) therapy allowed.
    
             11. If female, the subject must have a negative serum or urine pregnancy test at Screening
                 unless meeting non-productive potential criteria.
    
             12. Subjects must have hematologic and renal functions as specified: Absolute neutrophil
                 count ≥ 1500/mm3, platelets ≥ 100,000/mm3, Hgb ≥ 9.0g/dL, creatinine ≤ 1.7mg/dL, total
                 bilirubin ≤ 1.5mg/dL, blood urea nitrogen (BUN) within 2 times the upper limit of
                 normal, transaminases ≤ 4 times above the upper limits of the institutional norm.
    
             13. The subject or subject's medical power of attorney has provided written consent to
                 participate in this study.
    
            Exclusion Criteria:
    
              1. Subjects who had gross total tumor resection, partial resection, and/or debulking
                 surgery.
    
              2. Subjects must not have had prior RT, chemotherapy (including Gliadel wafer),
                 immunotherapy or therapy with a biologic agent, or hormonal therapy.
    
              3. Subject who is pregnant or lactating.
    
              4. Subject with a serious concurrent infection or medical illness that would jeopardize
                 the ability of the subject to receive study treatment with reasonable safety.
    
              5. Subject who cannot undergo MRI.
    
              6. Subject receiving concurrent chemotherapeutics or investigational agents within 30
                 days of study entry, including gliadel wafers or gliasite application.
    
              7. Subjects with other uncontrolled medical conditions, e.g. myocardial infarction,
                 cerebrovascular accident, diabetes or hypertension.
    
              8. Subjects diagnosed with another malignancy within 3 years prior to study start with
                 the exception of adequately treated basal cell carcinoma, squamous cell carcinoma,
                 non-melanomatous skin cancer or carcinoma in situ of the uterine cervix.
    
              9. CTCAE Version 4, Grade 4 non-hematological toxicity (except for alopecia, nausea,
                 vomiting).
          
    Maximum Eligible Age:70 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Overall Survival (OS)
    Time Frame:All subjects will be followed for 24 months
    Safety Issue:
    Description:Overall survival will be calculated from randomization to the time of death from any cause

    Secondary Outcome Measures

    Measure:Progression Free Survival (PFS)
    Time Frame:All subjects will be followed for 24 months
    Safety Issue:
    Description:Progression free survival will be calculated from the date of randomization to the date of first progression or death or last follow-up per Response Assessment in Neuro-Oncology (RANO) and modified RANO criteria
    Measure:Objective Response Rate (ORR)
    Time Frame:All subjects will be followed for 24 months
    Safety Issue:
    Description:Durable objective response rate (Complete Response [CR], Partial Response [PR]) will be estimated via radiological assessment per Response Assessment in Neuro-Oncology (RANO) and modified RANO criteria
    Measure:Karnofsky Performance Scale (KPS)
    Time Frame:All subjects will be followed for 24 months
    Safety Issue:
    Description:Functional status will be assessed by the investigators using the Karnofsky Performance Scale (KPS): total KPS scores range from 100 (normal), 90 (minor signs of disease), 80 (some sign or symptoms), 70 (unable to carry on normal activity), 60 (requires occasional assistance), 50 (requires considerable assistance), 40 (disabled), 30 (severely disabled), 29 (very sick), 10 (moribund) to 0 (dead); total KPS score will be used to assess eligibility at baseline (KPS > 60) and to assess subjects performance through the trial relative to baseline
    Measure:Quality of Life (EQ-5D-5L)
    Time Frame:All subjects will be followed for 24 months
    Safety Issue:
    Description:Quality of life will be assessed using the EQ-5D-5L visual analog scale: The EQ-5D-5L will be used by the subject to assess their view of their quality of life; This scale is numbered from 0 to 100 with 100 meaning the best health the subject can imagine to 0 meaning the worst health the subject can imagine; the subject will complete this scale at baseline and at the end of radiation treatment, again prior to and at the end of post-radiation treatment
    Measure:Corticosteroid Use
    Time Frame:All subjects will be followed for 24 months
    Safety Issue:
    Description:Corticosteroid medication use will be assessed throughout the trial

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Diffusion Pharmaceuticals Inc

    Last Updated

    January 18, 2018