Trial record 1 of 5 for:    VAL--083
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Safety Study of VAL-083 in Patients With Recurrent Malignant Glioma or Progressive Secondary Brain Tumor

This study is currently recruiting participants.
Verified September 2013 by DelMar Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
DelMar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01478178
First received: November 14, 2011
Last updated: September 6, 2013
Last verified: September 2013

November 14, 2011
September 6, 2013
October 2011
January 2014   (final data collection date for primary outcome measure)
Determination of maximum tolerated dose (MTD) [ Time Frame: Study Day 35 ] [ Designated as safety issue: Yes ]
The determination of MTD will be based on analysis of tolerance data from the first cycle of therapy in each dose group.
Same as current
Complete list of historical versions of study NCT01478178 on ClinicalTrials.gov Archive Site
  • Evaluate tumor response in patients with recurrent malignant glioma or progressive secondary brain tumor [ Time Frame: Every 60 days ] [ Designated as safety issue: No ]
    Tumor assessment every other treatment cycle, as long as patient continues to demonstrate response or stable disease and tolerates therapy.
  • Characterization of Cycle 1 plasma pharmacokinetics [ Time Frame: Cycle 1: 0, 0.25, 0.5, 1, 2, 4, 6 hrs and immediately prior to Cycle 1, Day 2 dosing ] [ Designated as safety issue: No ]
    Plasma will be analyzed to estimate appropriate PK parameters (Cmax, Tmax, AUC, elimination half-life, drug clearance, mean residence time, and volume of distribution).
  • Evaluate tumor response in patients with recurrent malignant glioma [ Time Frame: Every 60 days ] [ Designated as safety issue: No ]
    Tumor assessment every other treatment cycle, as long as patient continues to demonstrate response or stable disease and tolerates therapy.
  • Characterization of Cycle 1 plasma pharmacokinetics [ Time Frame: Cycle 1: 0, 0.25, 0.5, 1, 2, 4, 6 hrs and immediately prior to Cycle 1, Day 2 dosing ] [ Designated as safety issue: No ]
    Plasma will be analyzed to estimate appropriate PK parameters (Cmax, Tmax, AUC, elimination half-life, drug clearance, mean residence time, and volume of distribution).
Not Provided
Not Provided
 
Safety Study of VAL-083 in Patients With Recurrent Malignant Glioma or Progressive Secondary Brain Tumor
Open-label, Single Arm, Safety and Tolerability Dose Escalation Study of VAL-083 in Patients With Recurrent Malignant Glioma

The purpose of this Phase 1/2, open-label, single-arm study is to determine the safety and the maximal tolerated dose (MTD) of VAL-083 in patients with recurrent malignant glioma. Pharmacokinetic (PK) properties will be explored and tumor responses to treatment will be evaluated.

Recurrent glial tumors of the brain continue to be one of the most challenging malignancies to treat. Median survival for patients with recurrent disease is approximately 6 months for glioblastoma multiforme. Bevacizumab is used for treatment of recurrent disease; however patients who fail bevacizumab do not have many treatment options.

Metastases to the brain are the most common intracranial tumors in adults and occur ten times more frequently than primary brain tumors. It is estimated that 8 - 10% of cancer patients may develop symptomatic metastatic tumors in the brain. Systemic therapy is rarely used for primary treatment of brain metastases because many tumors that metastasize to the brain are not chemosensitive or have been already heavily pretreated with potentially effective agents, and poor penetration through the blood brain barrier is an additional concern.

Dianhydrogalactitol (DAG) rapidly penetrates both the cerebrospinal fluid (CSF) and the blood-brain barrier and accumulates in brain tissue. Clinical study of DAG in patients with GBM or with progressive secondary brain tumors is warranted. Patients with secondary brain metastases were allowed to enroll into the current protocol in Cohorts 2 and 3; however, enrollment ceased with Amendment 5 and will not be continued beyond Cohort 3.

This study will utilize a standard 3 + 3 dose escalation design, until the MTD or the maximum specified dose has been reached. In Phase 2, additional patients with GBM will be treated at the MTD (or other selected optimum Phase 2 dose) to measure tumor responses to treatment.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Glioma
  • Glioblastoma
  • Glioblastoma Multiforme
  • GBM
  • Brain Cancer
Drug: VAL-083
VAL-083 given by intravenous infusion with a starting dose of 1.5 mg/m2 IV. Escalating doses to be administered in sequential dose cohorts.
Experimental: VAL-083
VAL-083 given by intravenous infusion with a starting dose of 1.5 mg/m2 IV. Escalating doses to be administered in sequential dose cohorts.
Intervention: Drug: VAL-083
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
40
March 2014
January 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must be greater than or equal to 18 years old.
  • Histologically confirmed initial diagnosis of primary WHO Grade IV malignant glioma (glioblastoma), now recurrent; or Cohorts 2 and 3 only: progressive secondary brain tumor, has failed standard brain radiotherapy, and has brain tumor progression after at least one line of systemic therapy. Patients with progressive secondary brain tumors will not be enrolled under this protocol following the completion of Cohort 3.
  • If GBM, previously treated for GBM with surgery and/or radiation, if appropriate, and must have failed both bevacizumab (Avastin) and temozolomide (Temodar), unless either or both are contraindicated.
  • If GBM, greater than or equal to 12 weeks from radiotherapy, or 4 weeks if a new lesion, relative to the pre-radiation MRI, develops that is outside the primary radiation field.
  • Cohorts 2 & 3 only: Patients with secondary brain tumors must be greater than or equal to 4 weeks from radiotherapy. Patients with progressive secondary brain tumors will not be enrolled under this protocol following the completion of Cohort 3.
  • At least 4 weeks from last chemotherapy or bevacizumab (Avastin) therapy (6 weeks for nitrosourea or mitomycin C), or for chemotherapy regimes given continuously or on a weekly basis with limited potential for delayed toxicity, at least 2 weeks from last dose.
  • At least 21 days or 5 half-lives (whichever is shorter) since prior investigational anti-cancer drugs. A minimum of 10 days between termination of the investigational drug and administration of DAG is required
  • Recovered from all treatment-related toxicities to Grade 1 or less.
  • Must have a Karnofsky performance status of > 50 with a predicted life expectancy of at least 12 weeks.

Exclusion Criteria:

  • Current history of neoplasm other than the entry diagnosis. Patients with previous cancers treated and cured with local therapy alone may be considered with approval of the Medical Monitor.
  • Evidence of leptomeningeal spread of disease.
  • Evidence of recent hemorrhage on baseline MRI of the brain.
  • Concurrent severe, intercurrent illness.
  • History of severe cardiac disease.
  • Significant vascular disease.
  • History of stroke or transient ischemic attack within 6 months prior to beginning treatment.
  • Concomitant medications that are known inducers of CYP.
  • Concomitant medications that are strong inhibitors of cytochrome P450 and CYP3A up to 14 days before Cycle 1 Day 1 (pimozide, diltiazem, erythromycin, clarithromycin, and quinidine, and amiodarone up to 90 days before)
  • Known to be HIV positive or to have an AIDS-related illness.
  • Pregnant or breast feeding.
Both
18 Years and older
No
Not Provided
United States
 
NCT01478178
DLM-10-001
No
DelMar Pharmaceuticals, Inc.
DelMar Pharmaceuticals, Inc.
Not Provided
Principal Investigator: Howard A Burris, M.D. Sarah Cannon Research Institute; Nashville, Tennessee 37203, USA
Principal Investigator: Manish Patel, M.D. Florida Cancer Specialists, Sarasota, Florida 34232, USA
Principal Investigator: Nicholas Butowski, M.D. University of California, San Francisco, 94143, USA
DelMar Pharmaceuticals, Inc.
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP