Study of a Retroviral Replicating Vector to Treat Patients Undergoing Surgery for a Recurrent Malignant Brain Tumor
This study is currently recruiting participants.
Verified July 2012 by Tocagen Inc.
Sponsor:
Tocagen Inc.
Information provided by (Responsible Party):
Tocagen Inc.
ClinicalTrials.gov Identifier:
NCT01470794
First received: November 4, 2011
Last updated: May 17, 2013
Last verified: July 2012
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Purpose
This is a multicenter study evaluating the safety and tolerability of Toca 511, a retroviral replicating vector, injected into the resection cavity of patients with recurrent or progressive Grade III or Grade IV Gliomas who have elected to undergo surgical removal of their tumor. Approximately 7 weeks after injection of Toca 511, the patient will take an oral 8-day course of 5-FC, an antifungal antibiotic. These 8-day courses of 5-FC will be repeated a total of 3 times during the 6-month study. MRI scans will be performed approximately every 2 months. Three subjects will be evaluated at up to 4 dose levels of Toca 511. The dose of Toca 511 a patient receives will depend upon the number of previous study participants and how well they have tolerated the study drugs. All patients enrolled in this study will be encouraged to participate in a continuation protocol that enables additional 5-FC administration and the collection of long-term safety and response data.
| Condition | Intervention | Phase |
|---|---|---|
|
Glioblastoma Multiforme Anaplastic Astrocytoma Anaplastic Oligodendroglioma Anaplastic Oligoastrocytoma |
Biological: Toca 511 |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A P1 Ascending Dose Trial of the Safety and Tolerability of Toca 511, a Retroviral Replicating Vector, Administered to Subjects at the Time of Resection for Recurrent High Grade Glioma and Followed by Treatment With Toca FC, Extended-Release 5-FC |
Resource links provided by NLM:
Further study details as provided by Tocagen Inc.:
Primary Outcome Measures:
- Dose Limiting Toxicities [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]Excluding nausea, vomiting and fatigue, any Grade 3 or higher non-hematologic toxicity or any Grade 4 or higher hematologic toxicity, felt to be related to Toca 511 or the Toca 511/5-FC combination.
Secondary Outcome Measures:
- PFS-6 [ Time Frame: 6 months ] [ Designated as safety issue: No ]The percentage of subjects who have not progressed or died at 6 months.
| Estimated Enrollment: | 15 |
| Study Start Date: | January 2012 |
| Estimated Study Completion Date: | December 2013 |
| Estimated Primary Completion Date: | August 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Toca 511 vector
Toca 511 a retroviral replicating vector expressing the cytosine deaminase enzyme
|
Biological: Toca 511
All subjects will receive Toca 511, a retroviral replicating vector that expresses the cytosine deaminase (CD) gene. CD converts the antibiotic 5-FC to the anti-cancer drug 5-FU in cells that have been infected by the Toca 511 vector. Beginning approximately 7 weeks after administration of Toca 511, subjects will take an 8-day course of oral 5-FC. These 8-day courses of 5-FC are repeated every 7 weeks for a total of 3 courses during the 6-month study.
Other Names:
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Eligibility| Ages Eligible for Study: | 18 Years to 80 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria (must all be answered "Yes"):
- Has the subject given written informed consent?
- Is the subject between 18 and 80 years old inclusive?
- Has the subject undergone at least one prior surgical gross-total or subtotal tumor resection and a course of postoperative radiation therapy with concurrent temozolomide?
- Does the subject have a single tumor recurrence/progression that is < or = 6 cm in its greatest dimension?
- Based on pre-operative evaluation, is the tumor recurrence/progression a candidate for a resection of at least 80%?
- Has the subject elected not to undergo treatment with the Gliadel wafer?
- Does the subject have a Karnofsky performance status of at least 70%?
- Does the subjet have an absolute neutrophil count of at least 1500/mm^3?
- Does the subject have an absolute lymphocyte count of at least 500/mm^3?
- Does the subject have a platelet count of at least 100,000/mm^3?
- Does the subject have a Hgb of at least 10 g/dL?
- Does the subject have a normal PT/PTT?
- Does the subject have an estimated glomerular filtration rate of at least 50 mL/min by the Cockcroft-Gault formula?
- Does the subject have an ALT/AST < 3 times the upper limit of the lab reference range and a total bilirubin < 1.5 mg/dL?
- If the subject is a female of childbearing potential, has she had a negative serum pregnancy test within the past 21 days?
- For males and females, is the subject willing to use condoms for contraception for 6 months or until vector is no longer detected, whichever is longer?
- Is the subject willing and able to abide by the protocol?
Exclusion Criteria (must all be answered "No"):
- Has the subject received cytotoxic chemotherapy within the past 3 weeks (6 weeks for nitrosoureas) of the planned surgery date?
- Does the subject have, or has the subject had, within the past 4 weeks an infection requiring antibiotic, antifungal or antiviral therapy?
- Does the subject have any bleeding diathesis, or must the subject take any anticoagulants, or antiplatelet agents, including NSAIDs, that cannot be stopped for surgery?
- Does the subject have a history of allergy or intolerance to flucytosine?
- Is the subject HIV positive?
- Does the subject have any gastrointestinal disease that would prevent him/her from bing able to ingest or absorb flucytosine?
- Has the subject received any investigational treatment within the past 30 days?
- Is the subject breast feeding?
- Has the subject received Avastin (bevacizumab) for this recurrence/progression, within the past 5 weeks?
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01470794
Contacts
| Contact: Daniel Pertschuk, MD | 858-412-8409 | dpertschuk@tocagen.com |
| Contact: Tammy Boyce, MEd | 858-412-8416 | tboyce@tocagen.com |
Locations
| United States, California | |
| UCLA | Recruiting |
| Los Angeles, California, United States, 90095 | |
| Contact: Tim Cloughesy, MD 310-825-5321 | |
| Principal Investigator: Tim Cloughesy, MD | |
| University of California at San Diego | Recruiting |
| San Diego, California, United States, 92093 | |
| Contact: Brad Brown 858-822-5377 bdbrown@ucsd.edu | |
| Contact: Santosh Kesari, MD | |
| Principal Investigator: Santosh Kesari, MD | |
| United States, Michigan | |
| Henry Ford Hospital | Recruiting |
| Detroit, Michigan, United States, 48202 | |
| Contact: Sheryl Cummings, RN, BSN, OCN 313-916-3731 scummin3@hfhs.org | |
| Contact: Tiffany Pearce 313-916-1784 tpearce1@hfhs.org | |
| Principal Investigator: Tom Mikkelsen, MD | |
| United States, New Jersey | |
| JFK Medical Center | Recruiting |
| Edison, New Jersey, United States, 08820 | |
| Contact: Charles Porbeni, MD 732-321-7000 ext 68897 cporbeni@jfkhealth.org | |
| Principal Investigator: Joseph Landolfi, DO | |
| United States, Ohio | |
| Cleveland Clinic Foundation | Recruiting |
| Cleveland, Ohio, United States, 44195 | |
| Contact: Cathy Brewer, RN 216-444-7937 brewerc1@ccf.org | |
| Principal Investigator: Michael Vogelbaum, MD, PhD | |
| Ohio State University | Recruiting |
| Columbus, Ohio, United States, 43210 | |
| Contact: Jill Brown, MS 614-293-5554 jill.brown@osumc.edu | |
| Principal Investigator: James Elder, MD | |
| United States, Washington | |
| Swedish Neuroscience Institute | Recruiting |
| Seattle, Washington, United States, 98122 | |
| Contact: Nathan Hansen 206-320-3542 nathan.hansen@swedish.org | |
| Contact: Becky Wood 206-320-7115 becky.wood@swedish.org | |
| Principal Investigator: Greg Foltz, MD | |
Sponsors and Collaborators
Tocagen Inc.
More Information
No publications provided
| Responsible Party: | Tocagen Inc. |
| ClinicalTrials.gov Identifier: | NCT01470794 History of Changes |
| Other Study ID Numbers: | Tg 511-11-01 |
| Study First Received: | November 4, 2011 |
| Last Updated: | May 17, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Tocagen Inc.:
|
GBM HGG High grade glioma |
Malignant glioma Grade III glioma Grad IV glioma |
Additional relevant MeSH terms:
|
Astrocytoma Brain Neoplasms Glioblastoma Oligodendroglioma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Central Nervous System Neoplasms |
Nervous System Neoplasms Neoplasms by Site Brain Diseases Central Nervous System Diseases Nervous System Diseases Flucytosine Antifungal Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Antimetabolites Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on June 17, 2013