Safety Study of VAL-083 in Patients With Recurrent Malignant Glioma or Progressive Secondary Brain Tumor
This study is currently recruiting participants.
Verified February 2013 by Del Mar Pharmaceuticals (BC), LTD
Sponsor:
Del Mar Pharmaceuticals (BC), LTD
Information provided by (Responsible Party):
Del Mar Pharmaceuticals (BC), LTD
ClinicalTrials.gov Identifier:
NCT01478178
First received: November 14, 2011
Last updated: February 28, 2013
Last verified: February 2013
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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 or progressive secondary brain tumor. 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 or Progressive Secondary Brain Tumor |
Resource links provided by NLM:
Further study details as provided by Del Mar Pharmaceuticals (BC), LTD:
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: | 30 |
| Study Start Date: | October 2011 |
| Estimated Study Completion Date: | December 2013 |
| Estimated Primary Completion Date: | October 2013 (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.
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 or progressive secondary brain tumor 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 progressive secondary brain tumor, has failed standard brain radiotherapy, and has brain tumor progression after at least one line of systemic therapy.
- 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.
- Patients with secondary brain tumors must be greater than or equal to 4 weeks from radiotherapy.
- 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.
- Recovered from all treatment-related toxicities to Grade 1 or less.
- Must have 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.
- Prior treatment with prolifeprospan 20 with carmustine wafer (Gliadel wafer) within 60 days prior to first treatment (Day 0).
- Prior intracerebral agents.
- 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)
- Pregnant or breast feeding.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01478178
Locations
| 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 ASKSARAH@scresearch.net | |
| 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
Del Mar Pharmaceuticals (BC), LTD
Investigators
| Principal Investigator: | Howard A Burris, M.D. | Sarah Cannon Research Institute; Nashville, TN 37203, USA |
| Principal Investigator: | Manish Patel, M.D. | Florida Cancer Specialists, Sarasota, Florida 34232 |
More Information
No publications provided
| Responsible Party: | Del Mar Pharmaceuticals (BC), LTD |
| ClinicalTrials.gov Identifier: | NCT01478178 History of Changes |
| Other Study ID Numbers: | DLM-10-001 |
| Study First Received: | November 14, 2011 |
| Last Updated: | February 28, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Del Mar Pharmaceuticals (BC), LTD:
|
Glioma Glioblastoma Glioblastoma multiforme GBM brain tumor brain cancer recurrent brain tumor recurrent brain cancer refractory brain tumor refractory brain cancer recurrent GBM refractory GBM recurrent glioma refractory glioma recurrent glioblastoma |
refractory glioblastoma recurrent glioblastoma multiforme refractory glioblastom 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 Central Nervous System Neoplasms Nervous System Neoplasms Neoplasms by Site Neoplasms Brain Diseases Central Nervous System Diseases |
Nervous System Diseases Astrocytoma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue |
ClinicalTrials.gov processed this record on June 18, 2013