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Trans 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

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 (TSC) 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)

Harry N Cook, RPH/MBA

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.

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.

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

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

Overall survival will be calculated from randomization to the time of death from any cause

Diffusion Pharmaceuticals Inc

Trans 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: Trans Sodium Crocetinate (TSC) 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

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

The 100-206 trial was an open-label, dose-escalation safety run-in for what was originally planned as a larger randomized trial. 19 pts were enrolled to ensure that at least 8 pts completed the FDA-specified 24-mo. exposure period. At its Q3 2019 meeting, the DSMB found no adverse safety signal and recommended the trial continue as planned. However, the Sponsor did not have resources to fully support the randomized phase of the study and enrollment in the randomized phase was suspended.

Vice President of Clinical Operations

Overall Survival (OS)

Overall Study

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