Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Hypoxia

Glioma

Brain Neoplasms

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Channel Blockers

Anticonvulsants

All Drugs and Chemicals

Antineoplastic Agents

Phenytoin

Trans-sodium crocetinate

Antioxidants

Protective Agents

0.5 mg/kg TSC, anticonvulsants at Baseline - phenytoin only or none

0.75 mg/kg TSC, anticonvulsants at Baseline - phenytoin only or none

1.0 mg/kg TSC, anticonvulsants at Baseline - phenytoin only or none

Dose of TSC either 0.5 mg/kg, 0.75 mg/kg, or 1.0 mg/kg based on the Data Monitoring Committee decision, anticonvulsants at Baseline - phenytoin only or none

0.5 mg/kg TSC, anticonvulsants at Baseline - any except phenytoin-only or none

0.75 mg/kg TSC, anticonvulsants at Baseline - any except phenytoin-only or none

1.0 mg/kg TSC, anticonvulsants at Baseline - any except phenytoin-only or none

Dose of TSC either 0.5 mg/kg, 0.75 mg/kg, or 1.0 mg/kg based on the Data Monitoring Committee decision, anticonvulsants at Baseline - any except phenytoin-only or none

Single bolus intravenous administration in a superficial vein of the arm over a period of up to 2 minutes.

Trans Sodium Crocetinate (TSC)

The purpose of this study is to evaluate the impact of Trans Sodium Crocetinate (TSC) on oxygen levels in brain tumor tissue in patients with high grade glioma. The proposed clinical indication for TSC is a radiation sensitizer for the treatment of cancerous tumors.

In this open-label, one-site study, up to 48 patients with high grade glioma (HGG) who are undergoing biopsy or partial debulking of the tumor as part of standard of care will have an oxygen monitoring probe placed in residual tumor tissue. Oxygen levels in the tumor tissue will be measured prior to and after administering a single bolus injection of TSC. Safety assessments will occur throughout the trial, including at a 7 to 14 day follow-up visit. Pharmacokinetic assessments will be performed prior to and during the first 24 hours after TSC dosing.

Trans Sodium Crocetinate (TSC) Study of Intra-tumoral Oxygen Concentration, Safety, and Pharmacokinetics in Patients With High Grade Glioma

Open-label Study to Determine the Effect of Trans Sodium Crocetinate (TSC) on Intra-tumoral Oxygen Concentration, Tolerability, and Pharmacokinetics of TSC in Post-operative Patients With High Grade Glioma (HGG)

Diffusion Pharmaceuticals Inc

Kim M. Whitten, PharmD, RAC

Glioblastoma

Astrocytoma

Temozolomide

This was an open-label, sequential-cohort, dose-escalation study in two phases. Phase 1 was a safety run-in evaluating Trans Sodium Crocetinate (TSC) in 3 subjects who received 3 doses per week for 3 weeks (9 doses in total). Phase 2 engaged 56 subjects who received 3 doses per week for 6 weeks (18 doses in total). TSC was consistently dosed at 0.25mg/kg in both phases.

TSC administered intravenously as a bolus injection prior to radiation therapy sessions during 6 weeks of radiotherapy.

David R. Jones, M.D.

This open-label study evaluated the safety and efficacy of TSC when dosed concomitantly with the standard of care (radiation therapy and temozolomide) for newly diagnosed glioblastoma in adults. All patients received TSC in the study. The objective of the study was to evaluate the effect of TSC on survival and tumor response in patients with GBM while establishing an acceptable patient risk profile.

The overall objectives of this Phase 1/2 clinical study in newly diagnosed GBM patients was to evaluate the safety and tolerability, efficacy, PK profile, PFS/time to disease progression, QoL, and overall survival in adults when TSC is added to the standard of care regimen of radiation therapy and temozolomide. All patients received TSC in this study. The primary objective of the Phase 1 portion of the study was to evaluate the safety (DLT rate) and to define the dosing regimen of TSC for the larger Phase 2 study. The primary clinical endpoint was overall survival at 24 months and patients will be followed for up to 3 years.

Safety and Efficacy of Trans Sodium Crocetinate (TSC) With Radiation and Temozolomide in Newly Diagnosed Glioblastoma

Open-label Phase 1/2 (Safety Lead-in) Study of Trans Sodium Crocetinate (TSC) With Concomitant Treatment of Fractionated Radiation Therapy and Temozolomide in Newly Diagnosed Glioblastoma (GBM) Patients to Evaluate Safety and Efficacy

Number of Participants in Phase 1 with Dose Limiting Toxicities (DLTs)

Participants in phase 2 (18 dose group, 6 weeks treatment with TSC) were monitored for up to 3 years (last follow-up - February 16, 2016). Overall Survival (OS) was defined as the length of time from the date of tumor resection surgery or definitive biopsy to the date of death. The OS analyses were performed using the Kaplan-Meier estimate method. The OS rates at 6, 12, 18 and 24 months were estimated. Median OS values were calculated; a corresponding 95% confidence interval for each median value was determined using a log rank analysis. The length of OS (in months) was calculated as follows: date of death or censored - date of surgery or definitive biopsy / 30.4375.

The PFS analyses were performed using the Kaplan-Meier estimate method. The PFS rates at 6, 12, 18 and 24 months were estimated. Median PFS values were calculated; a corresponding 95% confidence interval for each median value was determined using a log rank analysis. Time to disease progression (in months) was calculated as follows: date of event\* or censoring - date of surgery or definitive biopsy / 30.4375; \*event = first tumor progression or death.

The sum of the product of the diameters of the tumor (using recorded tumor diameter measurements made from brain MRI images) was used to express tumor size. Results were summarized for actual and percentage change from baseline. Individual subjects results were listed, including tumor volume and tumor response from independent reviewers. Investigator data were listed but not used in the analysis. Percent response (according to independent reviewer assessments) by percentage tumor reduction from tumor resection or definitive biopsy to the last MRI were summarized.

This was an open-label, sequential cohort, dose escalation study designed to evaluate the safety and efficacy of TSC administered concomitantly with standard-of-care RT and temozolomide in adults with GBM. The study included two phases. Phase 1 was a safety run-in wherein 3 subjects received 9 doses at 3 doses per week for 3 weeks. Phase 2 engaged 56 patients who received 18 doses at 3 doses per week for 6 weeks. The dose of TSC was consistently 0.25mg/kg.

Phase 1: 3 weeks of TSC (9 doses in total) with concomitant RT and temozolomide for 6 weeks

TSC 0.25 mg/kg - 9 Dose Group

Phase 2: 6 weeks of TSC (18 doses in total) with concomitant RT and temozolomide for 6 weeks

TSC 0.25 mg/kg - 18 Dose Group

Trans Sodium Crocetinate (TSC): TSC administered intravenously as a bolus injection prior to radiation therapy sessions during 6 weeks of radiotherapy.

TSC 0.25 mg/kg for 9 or 18 Doses

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Count of participants

The baseline analysis population was the 56 patients in phase 2 given the comparison to historical control (Stupp 2005) wherein patients were treated for 6 weeks.

Chief Executive Officer

Dose limiting toxicities were only assessed for Phase 1 participants

Dose Limiting Toxicities (DLTs)

6 month OS

12 month OS

18 month OS

24 month OS

Trans Sodium Crocetinate (TSC): TSC administered intravenously for 18 doses as a bolus injection prior to radiation therapy sessions during 6 weeks of radiotherapy.

TSC 0.25 mg/kg - 18 Dose Group - Phase 2

All participants who received any amount of TSC and at least 1 session of RT (modified ITT)

Overall Survival

6 months

12 months

18 months

24 months

The analysis of PFS was performed in phase 2 only and included the modified ITT population which included 54 of the 56 subjects (98.2%) at the 2-year time point.

Progression-Free Survival (PFS)

tumor not reduced

0 to 39% tumor reduction

40 to 63% tumor reduction

64 to 93% tumor reduction

94 to 99% tumor reduction

100% tumor reduction

Phase 1 was the safety lead-in portion of the study conducted to evaluate an initial TSC dosage regimen in a smaller number of subjects and for a shorter period before a larger number of subjects were studied for a longer period in phase 2. Three (3) subjects were dosed with TSC at 0.25mg/kg for 3 weeks for a total of 9 doses with monitoring for dose-limiting toxicity (DLT). A Safety Monitoring Committee (SMC) evaluated the safety data and recommended TSC 0.25mg/kg for phase 2.

TSC 0.25mg/kg - 9 Dose Group - Phase 1

Of the 56 modified ITT population (subjects in the TSC 18 dose group) tumor size data exist for 37 subjects. Four (4) tumor-bearing subjects at baseline MRI did not have any post-baseline MRIs. Fourteen (14) subjects had a complete resection before baseline.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trans Sodium Crocetinate (TSC) Study of Intra-tumoral Oxygen Concentration, Safety, and Pharmacokinetics in Patients With High Grade Glioma	NCT00826930	High Grade Glio...	Trans Sodium Cr...	18 Years -	Diffusion Pharmaceuticals Inc
Trans Sodium Crocetinate (TSC) Study of Intra-tumoral Oxygen Concentration, Safety, and Pharmacokinetics in Patients With High Grade Glioma	NCT00826930	High Grade Glio...	Trans Sodium Cr...	18 Years -	Diffusion Pharmaceuticals Inc
Safety and Efficacy of Trans Sodium Crocetinate (TSC) With Radiation and Temozolomide in Newly Diagnosed Glioblastoma	NCT01465347	Glioblastoma GBM Glioma	Trans Sodium Cr...	18 Years -	Diffusion Pharmaceuticals Inc

Spots Global Cancer Trial Database for trans sodium crocetinate (tsc)