Clinical trial NCT01465347: Safety and Efficacy of Trans Sodium Crocetinate (TSC) With Radiation and Temozolomide in Newly Diagnosed Glioblastoma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Glioblastoma
GBM
Glioma
Keywords: Primary brain tumor
Glioblastoma
Glioma
GBM
Radiation therapy
Lead sponsor: Diffusion Pharmaceuticals Inc
Sponsor class: INDUSTRY
First posted: 2011-11-04
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Dose Limiting Toxicities (DLTs)
timeFrame: During phase 1
measure: Overall Survival
timeFrame: 6, 12, 18, 24 months
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 6,12,18, 24 months
measure: Number of Participants With Reduction in Tumor Size, According to Percentage of Tumor Reduction
timeFrame: From Baseline to Week 110
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: St. Joseph's Medical Center Barrow Neurology Clinics
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas Winthrop P. Rockefeller Cancer Institute
state: Arkansas
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Washington, D.C.
country: United States
facility: The George Washington University Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida McKnight Brain Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University Winship Cancer Institute
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Robert H. Lurie Comprehensive Cancer Center
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Lexington
country: United States
facility: University of Kentucky Markey Cancer Center
state: Kentucky
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: Winston-Salem
country: United States
facility: Forsyth Regional Cancer Center
state: North Carolina
city: Hershey
country: United States
facility: Penn State University Milton S. Hershey Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center Memorial Hermann Medical Center
state: Texas
city: Charlottesville
country: United States
facility: UVA Health Sciences Center Emily Couric Clinical Cancer Center
state: Virginia
city: Milwaukee
country: United States
facility: Froedtert & Medical College of Wisconsin Cancer Center
state: Wisconsin
Study officials:
affiliation: Diffusion Pharmaceuticals Inc
name: David R. Jones, M.D.
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.