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

Sponsor:	Diffusion Pharmaceuticals LLC
Information provided by:	Diffusion Pharmaceuticals LLC
ClinicalTrials.gov Identifier:	NCT00826930

Purpose

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.

Condition	Intervention	Phase
High Grade Glioma	Drug: Trans Sodium Crocetinate (TSC)	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	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)

Resource links provided by NLM:

MedlinePlus related topics: Brain Cancer Cancer Oxygen Therapy

U.S. FDA Resources

Further study details as provided by Diffusion Pharmaceuticals LLC:

Primary Outcome Measures:

Change from baseline in tumor tissue oxygen monitoring recordings [ Time Frame: Daily while inpatient ] [ Designated as safety issue: No ]
Safety assessments (laboratory tests) [ Time Frame: Daily while inpatient, 7-14 Day Follow-up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pharmacokinetic assessments [ Time Frame: Day 1, Day 2 ] [ Designated as safety issue: No ]
Tumor hypoxia biomarkers (HIF 1-alpha, osteopontin, carbonic anhydrase IX) [ Time Frame: Daily while inpatient ] [ Designated as safety issue: No ]

Enrollment:	1
Study Start Date:	March 2009
Study Completion Date:	May 2009
Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1A 0.5 mg/kg TSC, anticonvulsants at Baseline - phenytoin only or none	Drug: Trans Sodium Crocetinate (TSC) Single bolus intravenous administration in a superficial vein of the arm over a period of up to 2 minutes.
Experimental: 2A 0.75 mg/kg TSC, anticonvulsants at Baseline - phenytoin only or none	Drug: Trans Sodium Crocetinate (TSC) Single bolus intravenous administration in a superficial vein of the arm over a period of up to 2 minutes.
Experimental: 3A 1.0 mg/kg TSC, anticonvulsants at Baseline - phenytoin only or none	Drug: Trans Sodium Crocetinate (TSC) Single bolus intravenous administration in a superficial vein of the arm over a period of up to 2 minutes.
Experimental: 4A 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	Drug: Trans Sodium Crocetinate (TSC) Single bolus intravenous administration in a superficial vein of the arm over a period of up to 2 minutes.
Experimental: 1B 0.5 mg/kg TSC, anticonvulsants at Baseline - any except phenytoin-only or none	Drug: Trans Sodium Crocetinate (TSC) Single bolus intravenous administration in a superficial vein of the arm over a period of up to 2 minutes.
Experimental: 2B 0.75 mg/kg TSC, anticonvulsants at Baseline - any except phenytoin-only or none	Drug: Trans Sodium Crocetinate (TSC) Single bolus intravenous administration in a superficial vein of the arm over a period of up to 2 minutes.
Experimental: 3B 1.0 mg/kg TSC, anticonvulsants at Baseline - any except phenytoin-only or none	Drug: Trans Sodium Crocetinate (TSC) Single bolus intravenous administration in a superficial vein of the arm over a period of up to 2 minutes.
Experimental: 4B 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	Drug: Trans Sodium Crocetinate (TSC) Single bolus intravenous administration in a superficial vein of the arm over a period of up to 2 minutes.

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

At least 18 years old.
Prior histological diagnosis of high grade glioma (HGG) with prior initial treatment and radiation therapy for HGG; recurrence of HGG suspected, and care plan includes surgical procedure.
Undergoing surgical procedure for clinical reasons, and gross surgical resection not expected.
Neurosurgeon is planning stereotactic biopsy or tumor debulking for clinical reasons; frozen tissue confirmation of malignancy during this operative procedure is necessary.
Neurosurgeon evaluates that placement of oxygen monitoring probe after biopsy or debulking can be done safely without complications.
Contrast enhancing disease on MRI within 21 days prior to enrollment.
Karnofsky Performance Score ≥ 60 at Screening.
Recovered from toxicity of prior antineoplastic therapy, and off cytotoxic chemotherapy for 7 days prior to Screening.
Recovered from prior radiotherapy and had at least 21 days elapse since completion of radiotherapy prior to Screening.
Recovered from prior surgery for their brain tumor in investigator's clinical judgment.
If female, negative serum or urine pregnancy test at Screening.
Within 2 weeks of starting study, hematologic and renal functions as specified: Absolute neutrophil count ≥ 1500/mm3, platelets ≥ 100,000/mm3, hemoglobin ≥ 9.0g/dL, creatinine ≤ 1.7mg/dl, serum bilirubin ≤ 1.5mg/dL, blood urea nitrogen within 2 times the upper limit of normal, transaminases ≤ 4 times above the upper limits of the institutional norm, and prothrombin time and partial thromboplastin time within institutional norm or below.
Patient or patient's medical power of attorney provided written consent to participate in the study.
Mini Mental Status Exam score ≥ 15.

Exclusion Criteria:

Pregnant or lactating.
Receiving concurrent cytotoxic chemotherapy for their tumor within 7 days prior to Screening, or decision is made at the time of surgery to treat with other modality of treatment (e.g., gliadel wafers).
Serious concurrent infection or medical illness which would jeopardize the ability of the patient to safely participate.
Behavioral, cognitive, or psychiatric disease or personal situation that might interfere with optimal participation.
Cannot undergo an MRI.
Received an investigational drug not approved for human use by the FDA within 30 days of enrollment.
Previously received TSC.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00826930

Locations

United States, Maryland
Johns Hopkins Medical Institute/Johns Hopkins Hospital
Baltimore, Maryland, United States, 21205

Sponsors and Collaborators

Diffusion Pharmaceuticals LLC

More Information

No publications provided

Responsible Party:	Kim M. Whitten, PharmD, RAC, Diffusion Pharmaceuticals LLC
ClinicalTrials.gov Identifier:	NCT00826930 History of Changes
Other Study ID Numbers:	DP100-201
Study First Received:	January 21, 2009
Last Updated:	August 11, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by Diffusion Pharmaceuticals LLC:

High Grade Glioma
Brain Tumor
Solid Tumor
Partial Debulking

Tumor Resection
Tumor Tissue Hypoxia
Radiation Sensitizer
Cancerous Tumor

Additional relevant MeSH terms:

Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

Radiation-Sensitizing Agents
Vitamin A
Physiological Effects of Drugs
Pharmacologic Actions
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on February 09, 2012