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)

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.

Study Overview

• Status: Terminated
• Conditions: High Grade Glioma
• Intervention / Treatment: Drug: Trans Sodium Crocetinate (TSC)

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in tumor tissue oxygen monitoring recordings	Daily while inpatient
Safety assessments (laboratory tests)	Daily while inpatient, 7-14 Day Follow-up

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic assessments	Day 1, Day 2
Tumor hypoxia biomarkers (HIF 1-alpha, osteopontin, carbonic anhydrase IX)	Daily while inpatient

Collaborators and Investigators

• Sponsor: Diffusion Pharmaceuticals Inc

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): May 1, 2009

Study Registration Dates

• First Submitted: January 21, 2009
• First Submitted That Met QC Criteria: January 21, 2009
• First Posted (Estimate): January 22, 2009

Study Record Updates

• Last Update Posted (Estimate): August 12, 2010
• Last Update Submitted That Met QC Criteria: August 11, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: Brain Tumor; High Grade Glioma; Solid Tumor; Partial Debulking; Tumor Resection; Tumor Tissue Hypoxia; Radiation Sensitizer; Cancerous Tumor
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protective Agents; Antioxidants; Anticarcinogenic Agents; Trans-sodium crocetinate
• Other Study ID Numbers: DP100-201