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Safety Study of VAL-083 in Patients With Recurrent Malignant Glioma

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ClinicalTrials.gov Identifier: NCT01478178
Recruitment Status : Completed
First Posted : November 23, 2011
Last Update Posted : January 20, 2017
Sponsor:
Information provided by (Responsible Party):
Kintara Therapeutics, Inc. ( DelMar Pharmaceuticals, Inc. )

Tracking Information
First Submitted Date  ICMJE November 14, 2011
First Posted Date  ICMJE November 23, 2011
Last Update Posted Date January 20, 2017
Study Start Date  ICMJE October 2011
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 22, 2011)
Determination of maximum tolerated dose (MTD) [ Time Frame: Study Day 35 ]
The determination of MTD will be based on analysis of tolerance data from the first cycle of therapy in each dose group.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 22, 2011)
  • Evaluate tumor response in patients with recurrent malignant glioma [ Time Frame: Every 60 days ]
    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 ]
    Plasma will be analyzed to estimate appropriate PK parameters (Cmax, Tmax, AUC, elimination half-life, drug clearance, mean residence time, and volume of distribution).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety Study of VAL-083 in Patients With Recurrent Malignant Glioma
Official Title  ICMJE Open-label, Single Arm, Safety and Tolerability Dose Escalation Study of VAL-083 in Patients With Recurrent Malignant Glioma
Brief Summary 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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioma
  • Glioblastoma
  • Glioblastoma Multiforme
  • GBM
  • Brain Cancer
Intervention  ICMJE Drug: VAL-083 (Dianhydrogalactitol)
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.
Study Arms  ICMJE Experimental: VAL-083 (Dianhydrogalactitol)
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 (Dianhydrogalactitol)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 25, 2014)
55
Original Estimated Enrollment  ICMJE
 (submitted: November 22, 2011)
30
Actual Study Completion Date  ICMJE October 2016
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
  • Must have known MGMT methylation and IDH1 mutation status to be screened for study entry.

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01478178
Other Study ID Numbers  ICMJE DLM-10-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: The Clinical Study Report for this trial will be prepared and provided to U.S. F.D.A. as required by applicable regulatory requirement(s). Each participating trial investigator has been provided a copy their patient data captured in the electronic data base for this trial.
Responsible Party Kintara Therapeutics, Inc. ( DelMar Pharmaceuticals, Inc. )
Study Sponsor  ICMJE DelMar Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
Principal Investigator: Sani Kizilbash, M.D. Mayo Clinic, Rochester, Minnesota 55905, USA
Principal Investigator: Gerald Falchook, M.D. Sarah Cannon Research Institute; Denver, Colorado 80218 USA
PRS Account Kintara Therapeutics, Inc.
Verification Date January 2017

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