Study of a Retroviral Replicating Vector Given Intravenously to Patients Undergoing Surgery for Recurrent Brain Tumor

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Tocagen Inc.
Sponsor:
Information provided by (Responsible Party):
Tocagen Inc.
ClinicalTrials.gov Identifier:
NCT01985256
First received: November 8, 2013
Last updated: January 10, 2014
Last verified: January 2014
  Purpose

This is a multicenter study evaluating the safety and tolerability of Toca 511 administered intravenously to patients with recurrent or progressive Grade III or Grade IV Gliomas who have elected to undergo surgical removal of their tumor. Patients will receive ½ of the Toca 511 intravenously, followed approximately 11 days later by removal of the tumor and injection of the remaining ½ of the Toca 511 into the resection cavity. The tumor specimen will be tested for the presence of Toca 511. Approximately 4 weeks later, the patient will take an oral 10-day course of Toca FC, an antifungal antibiotic. These 10-day courses of Toca FC will be repeated approximately every 5 weeks until study completion. MRI scans will be performed approximately every 2 months. One subject each will be evaluated at 3 dose levels of Toca 511. Three subjects each will be evaluated in the 4th and 5th dosing cohorts. These cohorts will evaluate multiday intravenous administration of Toca 511: 3 consecutive days for the 4th cohort and 5 consecutive days for the 5th cohort. 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 Intravenously Prior to, and Intracranially at the Time of, Subsequent Resection for Recurrent HGG & Followed by Treatment With 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, weakness, 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: October 2013
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: December 2014 (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, intravenously and then intracranially. CD converts the antibiotic 5-fluorocytosine (5-FC) to the anti-cancer drug 5-fluorouracil (5-FU) in cells that have been infected by the Toca 511 vector. Beginning approximately 4 weeks after second administration of Toca 511, subjects will take an 10-day course of oral 5-FC. These 10-day courses of 5-FC are repeated every 5 weeks for the duration of the study.
Other Names:
  • vocimagene amiretrorepvec
  • retroviral replicating vector
  • 5-FC, flucytosine, 5-fluorocytosine
  • Toca FC

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Has the subject given written informed consent?
  2. Is the subject between 18 years old and 80 years old inclusive?
  3. Has the subject undergone at least one prior surgical gross-total or subtotal tumor resection with histologic confirmation of Grade III or IV glioma and a course of postoperative radiation therapy with concurrent temozolomide?
  4. Does the subject have a single, enhancing tumor recurrence/progression that is ≤ 8 cm in its greatest dimension?
  5. Based on the pre-operative evaluation, is the tumor recurrence/progression a candidate for ≥ 80% resection?
  6. Has the subject elected not to undergo treatment with the Gliadel® wafer?
  7. Does the subject have a Karnofsky performance status ≥ 70?
  8. Does the subject have an absolute neutrophil count (ANC) ≥ 1500/mm3?
  9. Does the subject have an absolute lymphocyte count ≥ 500/mm3?
  10. Does the subject have a platelet count ≥ 100,000/mm3?
  11. Does the subject have a Hgb ≥ 10 g/dL?
  12. Does the subject have a coagulation profile that would allow for the safe performance of surgery under general anesthesia?
  13. Does the subject have an estimated glomerular filtration rate of at least 50 mL/min (inclusive) by the Cockcroft-Gault formula?
  14. Does the subject have an ALT/AST < 3 times the upper limit of the laboratory reference range and total bilirubin < 1.5 mg/dL?
  15. If the subject is a female of childbearing potential, has she had a negative serum pregnancy test within the past 21 days?
  16. Is the subject willing to use condoms for contraception for 6 months after receiving Toca 511 or until there is no evidence of the virus in his/her blood, whichever is longer. If the subject is a fertile female, is she willing to use contraception for at least 12 months?
  17. Is the subject willing and able to abide by the protocol?
  18. Does the subject have adequate venous access?

Exclusion Criteria:

  1. Has the subject received cytotoxic chemotherapy within the past 3 weeks (6 weeks for nitrosoureas) of the planned date of vector injection?
  2. Does the subject have, or has the subject had, within the past 4 weeks any infection requiring antibiotic, antifungal or antiviral therapy?
  3. Has the subject received Avastin® (bevacizumab) for this recurrence/progression, or within the 4 weeks prior to planned Visit 1?
  4. Does the subject require corticosteroids prior to surgery to control cerebral edema?
  5. 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?
  6. Does the subject have a history of allergy or intolerance to flucytosine?
  7. Is the subject HIV positive?
  8. Does the subject have any gastrointestinal disease that would prevent him or her from being able to ingest or absorb flucytosine?
  9. Has the subject received any investigational treatment within the past 30 days?
  10. Is the subject 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: NCT01985256

Contacts
Contact: Daniel Pertschuk, MD 858-412-8409 dpertschuk@tocagen.com
Contact: Tammy Boyce, MEd 858-412-8416 tboyce@tocagen.com

Locations
United States, Michigan
Henry Ford Hospital Recruiting
Detroit, Michigan, United States, 48202
Contact: John Gaggin, RN, BSN    313-916-3731    jgaggin1@hfhs.org   
Contact: Tiffany Pearce    313-916-1784    tpearce1@hfhs.org   
Principal Investigator: Steven N Kalkanis, MD         
Sponsors and Collaborators
Tocagen Inc.
  More Information

No publications provided

Responsible Party: Tocagen Inc.
ClinicalTrials.gov Identifier: NCT01985256     History of Changes
Other Study ID Numbers: Tg 511-13-01
Study First Received: November 8, 2013
Last Updated: January 10, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Astrocytoma
Glioblastoma
Oligodendroglioma
Glioma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Flucytosine
Anti-Infective Agents
Antifungal Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014