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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01465347
Recruitment Status : Completed
First Posted : November 4, 2011
Results First Posted : July 14, 2017
Last Update Posted : July 14, 2017
Sponsor:
Information provided by (Responsible Party):
Diffusion Pharmaceuticals Inc

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Glioblastoma GBM Glioma Drug: Trans Sodium Crocetinate (TSC) Phase 1 Phase 2

Detailed Description:
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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 59 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : February 2012
Actual Primary Completion Date : November 2015
Actual Study Completion Date : February 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TSC 0.25 mg/kg for 9 or 18 doses
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.
Drug: Trans Sodium Crocetinate (TSC)
TSC administered intravenously as a bolus injection prior to radiation therapy sessions during 6 weeks of radiotherapy.
Other Name: TSC




Primary Outcome Measures :
  1. Dose Limiting Toxicities (DLTs) [ Time Frame: During phase 1 ]
    Number of Participants in Phase 1 with Dose Limiting Toxicities (DLTs)

  2. Overall Survival [ Time Frame: 6, 12, 18, 24 months ]
    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.


Secondary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: 6,12,18, 24 months ]
    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.

  2. Number of Participants With Reduction in Tumor Size, According to Percentage of Tumor Reduction [ Time Frame: From Baseline to Week 110 ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged at least 18 years of age; male or female. A patient who is 70 years of age or older may be considered for enrollment after review of patient clinical and laboratory data by the Protocol Medical Monitor.
  • Histologically confirmed diagnosis of GBM.
  • Contrast enhancing disease on MRI within 21 days prior to screening.
  • Karnofsky score (KPS) of ≥ 60 at Screening.
  • No prior RT, chemotherapy (including Gliadel wafer), immunotherapy or therapy with a biologic agent, or hormonal therapy. Glucocorticoid therapy is allowed.
  • Within 2 weeks of baseline visit, 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.
  • Sexually active patients must use an acceptable method of contraception while receiving doses of study medication.
  • Females of childbearing potential must have a negative serum or urine pregnancy test at screening and have additional pregnancy tests during study.

Exclusion Criteria:

  • Patient who cannot undergo MRI.
  • Pregnant or lactating.
  • Serious concurrent infection or medical illness that would jeopardize the ability of the patient to receive study treatment with reasonable safety.
  • Patient receiving concurrent chemotherapeutics or investigational agents within 30 days of baseline assessments, including gliadel wafers or gliasite application.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01465347


Locations
Show Show 18 study locations
Sponsors and Collaborators
Diffusion Pharmaceuticals Inc
Investigators
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Study Chair: David R. Jones, M.D. Diffusion Pharmaceuticals Inc

Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Diffusion Pharmaceuticals Inc
ClinicalTrials.gov Identifier: NCT01465347    
Other Study ID Numbers: DP100-202
First Posted: November 4, 2011    Key Record Dates
Results First Posted: July 14, 2017
Last Update Posted: July 14, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Diffusion Pharmaceuticals Inc:
Primary brain tumor
Glioblastoma
Glioma
GBM
Radiation therapy
Additional relevant MeSH terms:
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Glioblastoma
Glioma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Vitamin A
Temozolomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs