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Glioblastoma MultiformePhase 1NCT01470794

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

A Phase 1 study testing Toca 511 vector and Toca FC in people with Glioblastoma Multiforme and Anaplastic Astrocytoma, run by Tocagen Inc. at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
Toca 511 vector and Toca FC
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
8 sitesUnited States
Study dates
Feb 2012to 12 Apr 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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?
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  • 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?

Who cannot join

  • 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?
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  • 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?

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Ohio State University

    Columbus, Ohio, 43210

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • JFK Medical Center

    Edison, New Jersey, 08820

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • UCLA

    Los Angeles, California, 90095

  • University of California at San Diego

    San Diego, California, 92093

  • Swedish Neuroscience Institute

    Seattle, Washington, 98122

Other trials in United States

About this study

Official title: 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.

Being tested
Toca 511 vector, Toca FC
Keywords
GBM, HGG, High grade glioma, Malignant glioma, Grade III glioma, Grad IV glioma, glioma, glioblastoma, Grade IV astrocytoma, brain cancer, recurrent glioblastoma, AA, AOD, anaplastic astrocytoma, Anaplastic oligodendroglioma, Anaplastic oligoastrocytoma
Medical subject headings
Glioblastoma, Astrocytoma, Oligodendroglioma, Glioma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Toca 511 vectorBiological

    Also called Toca 511, RRV, retroviral replicating vector, 5-FC, flucytosine, 5-fluorocytosine, Toca FC

    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.

  • Toca FCDrug

    Also called flucytosine, 5-FC, 5-FC XR, Toca FC

Study groups in NCT01470794
Study groupRoleWhat they receive
Single ArmExperimentalToca 511 vector/Toca FC prodrug
Receives: Biological: Toca 511 vector; Drug: Toca FC

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Limiting Toxicities

    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.

    Measured: 2 months

Secondary outcomes (2)

  1. Overall Survival of Subjects

    Measured: Overall survival, Overall survival at 6 months (OS6), 9 months (OS9), and 12 months (OS12)

  2. Progression Free Survival (PFS) of Subjects

    Measured: PFS of subjects at 6 months (PFS-6)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Nov 2011 (estimated)
  2. Study startFeb 2012
  3. Primary completion12 Apr 2016
  4. Study completion12 Apr 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01470794
Sponsor's protocol ID
Tg 511-11-01
Status last verified
May 2018
First submitted
4 Nov 2011
Last updated
21 May 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • Ostertag D, Amundson KK, Lopez Espinoza F, Martin B, Buckley T, Galvao da Silva AP, Lin AH, Valenta DT, Perez OD, Ibanez 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.

    PubMed 22070930

  • Cloughesy TF, Landolfi J, Vogelbaum MA, Ostertag D, Elder JB, Bloomfield S, Carter B, Chen CC, Kalkanis SN, Kesari S, Lai A, Lee IY, Liau LM, Mikkelsen T, Nghiemphu P, Piccioni D, Accomando W, Diago OR, Hogan DJ, Gammon D, Kasahara N, Kheoh T, Jolly DJ, Gruber HE, Das A, Walbert T. Durable complete responses in some recurrent high-grade glioma patients treated with Toca 511 + Toca FC. Neuro Oncol. 2018 Sep 3;20(10):1383-1392. doi: 10.1093/neuonc/noy075.

    PubMed 29762717

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Toca 511 vector and Toca FC in people with Glioblastoma Multiforme and Anaplastic Astrocytoma, run by Tocagen Inc. at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Limiting Toxicities (time frame: 2 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01470794, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2018.

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