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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01985256
Recruitment Status : Completed
First Posted : November 15, 2013
Last Update Posted : May 21, 2018
Sponsor:
Information provided by (Responsible Party):
Tocagen Inc.

Tracking Information
First Submitted Date  ICMJE November 8, 2013
First Posted Date  ICMJE November 15, 2013
Last Update Posted Date May 21, 2018
Actual Study Start Date  ICMJE February 2014
Actual Primary Completion Date March 3, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 16, 2018)
Maximum feasible, safe, and tolerated dose of Toca 511 as measured by dose limiting toxicities. [ Time Frame: 32 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 8, 2013)
Dose Limiting Toxicities [ Time Frame: 2 months ]
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2018)
  • Measure Toca 511 deposition in tumor at the time of resection by QT-PCR [ Time Frame: At time of surgical resection ]
  • Measure how long Toca 511 stays in blood after IV administration by serum QT-PCR [ Time Frame: 10 days ]
  • Safety and tolerability of Toca FC given at various doses and schedules as measured by dose limiting toxicities. [ Time Frame: 32 weeks ]
  • Evaluate preliminary efficacy of Toca 511 and Toca FC by assessing overall survival, and tumor response rates. [ Time Frame: Overall survival, Overall survival at 6 months (OS6), 9 months (OS9), and 12 months (OS12) ]
  • Evaluate preliminary efficacy by assessing landmark PFS [6 months] [ Time Frame: 6 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 8, 2013)
PFS-6 [ Time Frame: 6 months ]
The percentage of subjects who have not progressed or died at 6 months.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of a Retroviral Replicating Vector Given Intravenously to Patients Undergoing Surgery for Recurrent Brain Tumor
Official Title  ICMJE A Phase 1 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
Brief Summary 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 meeting all of the inclusion and none of the exclusion criteria will receive an initial dose of Toca 511 administered as an intravenous, bolus injection, followed approximately 11 days later by an additional dose injected into the walls of the resection cavity at the time of planned tumor resection. Approximately 6 weeks later, patients will begin treatment with oral Toca FC, an antifungal agent, and repeated every 4 weeks. All patients enrolled in this study will be encouraged to participate in a continuation protocol that enables additional Toca FC administration and the collection of long-term safety and response data.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioblastoma Multiforme
  • Anaplastic Astrocytoma
  • Anaplastic Oligodendroglioma
  • Anaplastic Oligoastrocytoma
Intervention  ICMJE
  • Biological: Toca 511
    All patients will receive Toca 511, a retroviral replicating vector that expresses the cytosine deaminase (CD) gene, intravenously and then intracranially. CD converts the antifungal 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 6 weeks after the second administration of Toca 511,patients will begin 7-day course of oral 5-FC, repeated every 4 weeks for the duration of the study.
    Other Names:
    • vocimagene amiretrorepvec
    • retroviral replicating vector (RRV)
  • Drug: Toca FC
    Other Name: flucytosine, 5-FC, 5-FC XR, Toca FC
Study Arms  ICMJE Experimental: Single Arm
Toca 511 vector/Toca FC
Interventions:
  • Biological: Toca 511
  • Drug: Toca FC
Publications * Ostertag D, Amundson KK, Lopez Espinoza F, Martin B, Buckley T, Galvão da Silva AP, Lin AH, Valenta DT, Perez OD, Ibañez CE, Chen CI, Pettersson PL, Burnett R, Daublebsky V, Hlavaty J, Gunzburg W, Kasahara N, Gruber HE, Jolly DJ, Robbins JM. Brain tumor eradication and prolonged survival from intratumoral conversion of 5-fluorocytosine to 5-fluorouracil using a nonlytic retroviral replicating vector. Neuro Oncol. 2012 Feb;14(2):145-59. doi: 10.1093/neuonc/nor199. Epub 2011 Nov 9.

*   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: February 23, 2016)
17
Original Estimated Enrollment  ICMJE
 (submitted: November 8, 2013)
15
Actual Study Completion Date  ICMJE March 3, 2016
Actual Primary Completion Date March 3, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Has the subject given written informed consent?
  • Is the subject between 18 years old and 80 years old inclusive?
  • Has the subject had histologically proven HGG with recurrence or progression following initial definitive therapy(s) such as surgery with or without adjuvant radiation therapy and/or chemotherapy (confirmed by diagnostic biopsy or contrast-enhanced MRI and evaluable by Macdonald criteria)? Note, if first recurrence of HGG is documented by MRI, an interval of at least 12 weeks after the end of prior radiation therapy is required unless there is either: i) histopathologic confirmation of recurrent tumor, or ii) new enhancement on MRI outside of the radiotherapy treatment field.
  • Does the patient have either (1) a single, enhancing tumor recurrence/progression that is ≤ 8 cm in greatest dimension, or (2) multiple enhancing tumor recurrences/progressions within the same surgical field where the sum of their greatest dimensions is ≤ 8 cm?
  • Based on the pre-operative evaluation, is the tumor recurrence/progression a candidate for ≥ 80% resection?
  • Has the subject elected not to undergo treatment with the Gliadel® wafer?
  • Does the subject have a Karnofsky performance status ≥ 70?
  • Does the subject have an absolute neutrophil count (ANC) ≥ 1500/mm3?
  • Does the subject have an absolute lymphocyte count ≥ 500/mm3?
  • Does the subject have a platelet count ≥ 100,000/mm3?
  • Does the subject have a Hgb ≥ 10 g/dL?
  • Does the subject have a coagulation profile that would allow for the safe performance of surgery under general anesthesia?
  • Does the subject have an estimated glomerular filtration rate of at least 50 mL/min (inclusive) by the Cockcroft-Gault formula?
  • Does the subject have an ALT < 3 times the upper limit of the laboratory reference range and 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?
  • 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?
  • Is the subject willing and able to abide by the protocol?
  • Does the subject have adequate venous access?

Exclusion Criteria:

  • Has the subject received cytotoxic chemotherapy within the past 3 weeks (6 weeks for nitrosoureas) of the planned date of vector injection?
  • Does the subject have, or has the subject had, within the past 4 weeks any infection requiring antibiotic, antifungal or antiviral therapy?
  • Has the subject received Avastin® (bevacizumab) for this recurrence/progression, or within the 4 weeks prior to planned Visit 1?
  • 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 or her from being able to swallow or absorb flucytosine?
  • Has the subject received any investigational treatment within the past 30 days?
  • Is the subject breastfeeding?
  • Does the patient have a history of prior malignancy, excluding basal or squamous cell carcinoma of the skin, with an expected survival of less than five years?
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (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 NCT01985256
Other Study ID Numbers  ICMJE Tg 511-13-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Tocagen Inc.
Study Sponsor  ICMJE Tocagen Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Asha Das, MD Tocagen Inc.
Principal Investigator: Steven Kalkanis, MD Henry Ford Hospital
PRS Account Tocagen Inc.
Verification Date May 2018

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