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

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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.

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.

Condition or disease Intervention/treatment Phase
Glioblastoma Multiforme Anaplastic Astrocytoma Anaplastic Oligodendroglioma Anaplastic Oligoastrocytoma Biological: Toca 511 Drug: Toca FC Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 17 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : February 2014
Actual Primary Completion Date : March 3, 2016
Actual Study Completion Date : March 3, 2016


Arm Intervention/treatment
Experimental: Single Arm
Toca 511 vector/Toca FC
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




Primary Outcome Measures :
  1. Maximum feasible, safe, and tolerated dose of Toca 511 as measured by dose limiting toxicities. [ Time Frame: 32 weeks ]

Secondary Outcome Measures :
  1. Measure Toca 511 deposition in tumor at the time of resection by QT-PCR [ Time Frame: At time of surgical resection ]
  2. Measure how long Toca 511 stays in blood after IV administration by serum QT-PCR [ Time Frame: 10 days ]
  3. Safety and tolerability of Toca FC given at various doses and schedules as measured by dose limiting toxicities. [ Time Frame: 32 weeks ]
  4. 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) ]
  5. Evaluate preliminary efficacy by assessing landmark PFS [6 months] [ Time Frame: 6 months ]


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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?

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01985256


Locations
United States, California
UC Irivine
Irvine, California, United States, 92868
UCLA
Los Angeles, California, United States, 90095
UC San Diego, Moores Cancer Center
San Diego, California, United States, 92093
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, New Jersey
JFK Medical Center New Jersery
Edison, New Jersey, United States, 08818
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Tocagen Inc.
Investigators
Study Director: Asha Das, MD Tocagen Inc.
Principal Investigator: Steven Kalkanis, MD Henry Ford Hospital

Publications:
Responsible Party: Tocagen Inc.
ClinicalTrials.gov Identifier: NCT01985256     History of Changes
Other Study ID Numbers: Tg 511-13-01
First Posted: November 15, 2013    Key Record Dates
Last Update Posted: May 21, 2018
Last Verified: May 2018

Keywords provided by Tocagen Inc.:
anaplastic oligodendroglioma
glioma
glioblastoma
glioblastoma multiforme
Grade IV astrocytoma
brain cancer
recurrent glioblastoma
GBM
AA
AOD
anaplastic astrocytoma
anaplastic oligoastrocytoma
malignant glioma
high grade glioma

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Oligodendroglioma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue