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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. (see Contacts and Locations)
Verified September 2014 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 25, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Glioma
Glioblastoma
Glioblastoma Multiforme
GBM
Brain Cancer
Drug: VAL-083
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-label, Single Arm, Safety and Tolerability Dose Escalation Study of VAL-083 in Patients With Recurrent Malignant Glioma

Resource links provided by NLM:


Further study details as provided by DelMar Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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).


Estimated Enrollment: 55
Study Start Date: October 2011
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.

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.

  Eligibility

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

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01478178

Locations
United States, California
University of California, San Francisco, Division of Neuro-Oncology Recruiting
San Francisco, California, United States, 94143
Contact: Nicholas Butowski, M.D.    415-353-2966    Butowski@neurosurg.ucsf.edu   
Contact: Claire Rein-Weston    (415) 353-2372    Rein-Weston@neurosurg.ucsf.edu   
Principal Investigator: Nicholas Butowski, M.D.         
United States, Florida
Florida Cancer Specialists Recruiting
Sarasota, Florida, United States, 34232
Contact: Manish Patel, M.D.    941-377-9993    mpatel@flcancer.com   
Contact: Heather Rieth    (941) 377-9993    hrieth@flcancer.com   
Principal Investigator: Manish Patel, M.D.         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Howard A Burris, M.D.    877-691-7274    hburris@tnonc.com   
Contact: Lorie Patterson    (615) 329-7289    Lorie.patterson@scresearch.net   
Principal Investigator: Howard A Burris, M.D.         
Sub-Investigator: Kent Shih, M.D.         
Sponsors and Collaborators
DelMar Pharmaceuticals, Inc.
Investigators
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
  More Information

No publications provided

Responsible Party: DelMar Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01478178     History of Changes
Other Study ID Numbers: DLM-10-001
Study First Received: November 14, 2011
Last Updated: September 25, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by DelMar Pharmaceuticals, Inc.:
brain tumor
brain cancer
recurrent brain tumor
recurrent brain cancer
refractory brain tumor
refractory brain cancer
Glioma
Glioblastoma
Glioblastoma multiforme
GBM
recurrent GBM
refractory GBM
recurrent glioma
refractory glioma
recurrent glioblastoma
refractory glioblastoma
recurrent glioblastoma multiforme
refractory glioblastoma multiforme
failed temodar
failed temozolomide
temodar refractory
temozolomide refractory
failed avastin
avastin refractory
failed bevacizumab
bevacizumab refractory
avastin failure
bevacizumab failure
temodar failure
temozolomide failure

Additional relevant MeSH terms:
Brain Neoplasms
Glioblastoma
Glioma
Astrocytoma
Brain Diseases
Central Nervous System Diseases
Central Nervous System Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Nervous System Diseases
Nervous System Neoplasms
Neuroectodermal Tumors

ClinicalTrials.gov processed this record on November 24, 2014