GlioblastomaPhase 1/2NCT01465347

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

A Phase 1/2 study testing Trans Sodium Crocetinate (TSC) in people with Glioblastoma and GBM, run by Diffusion Pharmaceuticals Inc at 18 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Glioblastoma, GBM, Glioma
What is being tested?: Trans Sodium Crocetinate (TSC)
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 59 participants
Where: 18 sitesUnited States
Study dates: Feb 2012to Feb 2016
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

18 sites in 1 country.

City, postcode or hospital

18 sites in 1 country

United States18 sites

Emory University Winship Cancer Institute
Atlanta, Georgia, 30322
Medical University of South Carolina
Charleston, South Carolina, 29425
UVA Health Sciences Center Emily Couric Clinical Cancer Center
Charlottesville, Virginia, 22908
Northwestern University Robert H. Lurie Comprehensive Cancer Center
Chicago, Illinois, 60611
Rush University Medical Center
Chicago, Illinois, 60612
Baylor University Medical Center
Dallas, Texas, 75246
University of Florida McKnight Brain Institute
Gainesville, Florida, 32611
Penn State University Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
University of Texas Health Science Center Memorial Hermann Medical Center
Houston, Texas, 77030
University of Kentucky Markey Cancer Center
Lexington, Kentucky, 40536
University of Arkansas Winthrop P. Rockefeller Cancer Institute
Little Rock, Arkansas, 72205
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Cedars-Sinai Medical Center
Los Angeles, California, 90048
North Shore University Hospital
Manhasset, New York, 11030
Froedtert & Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, 53226
St. Joseph's Medical Center Barrow Neurology Clinics
Phoenix, Arizona, 85013
The George Washington University Medical Center
Washington D.C., District of Columbia, 20037
Forsyth Regional Cancer Center
Winston-Salem, North Carolina, 27103

Other trials in United States

About this study

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

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.

Read the 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.

Conditions: Glioblastoma, GBM, Glioma
Being tested: Trans Sodium Crocetinate (TSC)
Keywords: Primary brain tumor, Glioblastoma, Glioma, GBM, Radiation therapy
Medical subject headings: Glioblastoma, Glioma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT01465347
Study group	Role	What they receive
TSC 0.25 mg/kg for 9 or 18 doses	Experimental	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. Receives: Drug: Trans Sodium Crocetinate (TSC)

What is being measured

The primary outcome is the main question the study is designed to answer.

Dose Limiting Toxicities (DLTs)
Number of Participants in Phase 1 with Dose Limiting Toxicities (DLTs)
Measured: During phase 1
Overall Survival
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.
Measured: 6, 12, 18, 24 months

Secondary outcomes (2)

Progression-Free Survival (PFS)
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.
Measured: 6,12,18, 24 months
Number of Participants With Reduction in Tumor Size, According to Percentage of Tumor Reduction
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.
Measured: From Baseline to Week 110

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2012Feb 2016

First posted4 Nov 2011 (estimated)
Study startFeb 2012
Primary completionNov 2015
Study completionFeb 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for GlioblastomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 59 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01465347
Sponsor's protocol ID: DP100-202
Status last verified: Jun 2017
First submitted: 2 Nov 2011
Last updated: 14 Jul 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Publications

Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330.
PubMed 15758009
Gainer JL, Sheehan JP, Larner JM, Jones DR. Trans sodium crocetinate with temozolomide and radiation therapy for glioblastoma multiforme. J Neurosurg. 2017 Feb;126(2):460-466. doi: 10.3171/2016.3.JNS152693. Epub 2016 May 13.
PubMed 27177177

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 14 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01465347
Acronym / sponsor ID: DP100-202
Conditions: Glioblastoma, GBM, Glioma
Keywords: Primary brain tumor, Glioblastoma, Glioma, GBM, Radiation therapy
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 59 participants (actual)
Lead sponsor: Diffusion Pharmaceuticals IncIndustry (pharma, biotech, devices)
Study start: Feb 2012
Primary completion: Nov 2015 (actual)
Study completion: Feb 2016 (actual)
First posted: 4 Nov 2011 (estimated)
Results: Posted 14 Jul 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
TSC 0.25 mg/kg for 9 or 18 doses	Experimental	Drug: Trans Sodium Crocetinate (TSC)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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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.

Key exclusion criteria (4 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Trans Sodium Crocetinate (TSC)Also: TSCTSC administered intravenously as a bolus injection prior to radiation therapy sessions during 6 weeks of radiotherapy.	Drug	TSC 0.25 mg/kg for 9 or 18 doses

Primary outcome

Dose Limiting Toxicities (DLTs)
Time frame: During phase 1
Number of Participants in Phase 1 with Dose Limiting Toxicities (DLTs)
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.

2 secondary outcomes

Progression-Free Survival (PFS)
Time frame: 6,12,18, 24 months
Number of Participants With Reduction in Tumor Size, According to Percentage of Tumor Reduction
Time frame: From Baseline to Week 110

Results and safety

Results posted to the registry on 14 Jul 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
TSC 0.25 mg/kg - 9 Dose Group	3	2
TSC 0.25 mg/kg - 18 Dose Group	56	53

Primary outcome: Dose Limiting Toxicities (DLTs)

Time frame: During phase 1. Count of participants. Unit: Participants

Measure	TSC 0.25 mg/kg - 9 Dose Group n = 3	TSC 0.25 mg/kg - 18 Dose Group n = 0
Value	0	–

Population analysed: Dose limiting toxicities were only assessed for Phase 1 participants

Primary outcome: Overall Survival

Time frame: 6, 12, 18, 24 months. Number (95% Confidence Interval). Unit: participants

Measure	TSC 0.25 mg/kg - 18 Dose Group - Phase 2 n = 56
6 month OS	89.3 (81.18 to 97.39)
12 month OS	71.2 (59.22 to 83.09)
18 month OS	43.8 (30.67 to 56.90)
24 month OS	36.3 (23.55 to 49.08)

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

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: The first subject was enrolled February 27, 2012 and the last subject completed treatment on April 28, 2015. The last follow-up of the last subject was February 16, 2016. Adverse events were collected from the first dose of TSC to 30 days following the last dose (week 10 study visit). Subjects who experienced multiple events with the same preferred term were counted once for that preferred term.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
TSC 0.25 mg/kg - 9 Dose Group	1 of 3 (33.3%)	3 of 3 (100%)	Not reported
TSC 0.25 mg/kg - 18 Dose Group	10 of 56 (17.9%)	56 of 56 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 15758009Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330.
Derived from this study: PubMed 27177177Gainer JL, Sheehan JP, Larner JM, Jones DR. Trans sodium crocetinate with temozolomide and radiation therapy for glioblastoma multiforme. J Neurosurg. 2017 Feb;126(2):460-466. doi: 10.3171/2016.3.JNS152693. Epub 2016 May 13.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

David R. Jones, M.D. study chair

Diffusion Pharmaceuticals Inc

18 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Trans Sodium Crocetinate (TSC) in people with Glioblastoma and GBM, run by Diffusion Pharmaceuticals Inc at 18 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Limiting Toxicities (DLTs) (time frame: During phase 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01465347, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2017; AzTrials last refreshed its copy on 8 Nov 2026.