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Study of a Retroviral Replicating Vector Combined With a Prodrug to Treat Patients Undergoing Surgery for a Recurrent Malignant Brain Tumor

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ClinicalTrials.gov Identifier: NCT01470794
Recruitment Status : Completed
First Posted : November 11, 2011
Last Update Posted : May 21, 2018
Sponsor:
Information provided by (Responsible Party):
Tocagen Inc.

November 4, 2011
November 11, 2011
May 21, 2018
February 2012
April 12, 2016   (Final data collection date for primary outcome measure)
Dose Limiting Toxicities [ Time Frame: 2 months ]
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/Toca FC combination.
Dose Limiting Toxicities [ Time Frame: 2 months ]
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.
Complete list of historical versions of study NCT01470794 on ClinicalTrials.gov Archive Site
  • Overall Survival of Subjects [ Time Frame: Overall survival, Overall survival at 6 months (OS6), 9 months (OS9), and 12 months (OS12) ]
  • Progression Free Survival (PFS) of Subjects [ Time Frame: PFS of subjects at 6 months (PFS-6) ]
PFS-6 [ Time Frame: 6 months ]
The percentage of subjects who have not progressed or died at 6 months.
Not Provided
Not Provided
 
Study of a Retroviral Replicating Vector Combined With a Prodrug to Treat Patients Undergoing Surgery for a Recurrent Malignant Brain Tumor
A Phase 1 Ascending Dose Trial of Safety and Tolerability of Toca 511, a Retroviral Replicating Vector, Administered to Subjects at the Time of Resection for Recurrent High Grade Glioma & Followed by Treatment With Toca FC, Extended-Release 5-FC
This is a multicenter study evaluating the safety and tolerability of increasing doses of Toca 511, a retroviral replicating vector, injected into the resection cavity of patients with Grade III or Grade IV Gliomas who have elected to undergo surgical removal of their tumor. Approximately 6 weeks after injection of Toca 511, patients will begin an oral courses of Toca FC, an antifungal agent. These one week courses of Toca FC will be repeated during the approximately 30 week study. Two separate cohorts of patients treated with Toca 511 and Toca FC will also be evaluated with either of the following standard treatments for glioma: lomustine or bevacizumab. After completion of this study, all patients will be eligible for enrollment and encouraged to enter a long-term continuation protocol that enables additional Toca FC treatment cycles to be given, as well as permits the collection of long-term safety and survival data.
Not Provided
Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Glioblastoma Multiforme
  • Anaplastic Astrocytoma
  • Anaplastic Oligodendroglioma
  • Anaplastic Oligoastrocytoma
  • Biological: Toca 511 vector
    All patients will receive Toca 511, a retroviral replicating vector that expresses the cytosine deaminase (CD) gene. CD converts the antifungal 5-FC to the anti-cancer drug 5-FU in cells that have been infected by the Toca 511 vector. Beginning approximately 6 weeks after administration of Toca 511, patients will begin courses of oral Toca FC at pre-specified intervals, depending on cohort, during the approximately 30 week study.
    Other Names:
    • Toca 511, RRV, retroviral replicating vector
    • 5-FC, flucytosine, 5-fluorocytosine, Toca FC
  • Drug: Toca FC
    Other Name: flucytosine, 5-FC, 5-FC XR, Toca FC
Experimental: Single Arm
Toca 511 vector/Toca FC prodrug
Interventions:
  • Biological: Toca 511 vector
  • Drug: Toca FC
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.
 
Completed
58
15
April 12, 2016
April 12, 2016   (Final data collection date for primary outcome measure)

Inclusion Criteria (must all be answered "Yes"):

  • Has the patient given written informed consent?
  • Is the patient between 18 years old and 80 years old inclusive?
  • Has the patient 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 GBM 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 a single, HGG tumor recurrence/progression that is ≤ 5 cm in its greatest dimension?
  • Based on the pre-operative evaluation, is the tumor recurrence/progression a candidate for ≥ 80% resection?
  • Has the patient elected not to undergo treatment with the Gliadel® wafer?
  • Does the patient have a Karnofsky performance status ≥ 70?
  • Does the patient have an absolute neutrophil count (ANC) ≥ 1500/mm3?
  • Does the patient have an absolute lymphocyte count ≥ 500/mm3?
  • Does the patient have a platelet count ≥ 100,000/mm3?
  • Does the patient have a Hgb ≥ 10 g/dL?
  • Does the patient have a normal PT/PTT? (subnormal PT/PTT acceptable)
  • Does the patient have an estimated glomerular filtration rate of at least 50 mL/min (inclusive) by the Cockcroft-Gault formula?
  • Does the patient have an ALT < 3 times the upper limit of the laboratory reference range and total bilirubin < 1.5 mg/dL?
  • If the patient is a female of childbearing potential, has she had a negative serum pregnancy test within the past 21 days?
  • Is the patient 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 patient is a fertile female, is she willing to use contraception for at least 12 months?
  • Is the patient willing and able to abide by the protocol?

Exclusion Criteria (must all be answered "No"):

  • Has the patient received cytotoxic chemotherapy within the past 3 weeks (6 weeks for nitrosoureas) of the planned surgery date?
  • Does the patient have, or has the subject had, within the past 4 weeks any infection requiring antibiotic, antifungal or antiviral therapy?
  • Has the patient had a surgical procedure in the last 28 days or a surgical wound that is not healed?
  • Does the patient have any bleeding diathesis, or must the subject take any anticoagulants, or antiplatelet agents, including NSAIDs that cannot be stopped for surgery?
  • Does the patient have a history of allergy or intolerance to flucytosine?
  • Is the patient HIV positive?
  • Does the patient have any gastrointestinal disease that would prevent him or her from being able to ingest or absorb flucytosine?
  • Has the patient received any investigational treatment within the past 30 days?
  • Is the patient breast feeding?
  • Has the patient received Avastin® (bevacizumab) for this recurrence/progression, or within the past 5 weeks?
  • 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?
Sexes Eligible for Study: All
18 Years to 80 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01470794
Tg 511-11-01
Yes
Not Provided
Not Provided
Tocagen Inc.
Tocagen Inc.
Not Provided
Study Director: Asha Das, MD Tocagen Inc.
Principal Investigator: Timothy Cloughesy, MD, NO University of California, Los Angeles
Tocagen Inc.
May 2018

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