Glioblastoma MultiformePhase 1NCT01985256
Study of a Retroviral Replicating Vector Given Intravenously to Patients Undergoing Surgery for Recurrent Brain Tumor
A Phase 1 study testing Toca 511 and Toca FC in people with Glioblastoma Multiforme and Anaplastic Astrocytoma, run by Tocagen Inc. at 6 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Glioblastoma Multiforme, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma
- What is being tested?
- Toca 511 and Toca FC
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 6 sitesUnited States
- Study dates
- Feb 2014to 3 Mar 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 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?
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- 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?
Who cannot join
- 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?
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- 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?
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Henry Ford Hospital
Detroit, Michigan, 48202
JFK Medical Center New Jersery
Edison, New Jersey, 08818
UC Irivine
Irvine, California, 92868
UCLA
Los Angeles, California, 90095
UC San Diego, Moores Cancer Center
San Diego, California, 92093
About this study
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
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.
- Conditions
- Glioblastoma Multiforme, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Anaplastic Oligoastrocytoma
- Being tested
- Toca 511, Toca FC
- Keywords
- glioma, glioblastoma, glioblastoma multiforme, Grade IV astrocytoma, brain cancer, recurrent glioblastoma, GBM, AA, AOD, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic oligoastrocytoma, malignant glioma, high grade glioma
- 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 511Biological
Also called vocimagene amiretrorepvec, retroviral replicating vector (RRV)
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.
Toca FCDrug
Also called flucytosine, 5-FC, 5-FC XR, Toca FC
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | Toca 511 vector/Toca FC Receives: Biological: Toca 511; Drug: Toca FC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum feasible, safe, and tolerated dose of Toca 511 as measured by dose limiting toxicities.
Measured: 32 weeks
Secondary outcomes (5)
Measure Toca 511 deposition in tumor at the time of resection by QT-PCR
Measured: At time of surgical resection
Measure how long Toca 511 stays in blood after IV administration by serum QT-PCR
Measured: 10 days
Safety and tolerability of Toca FC given at various doses and schedules as measured by dose limiting toxicities.
Measured: 32 weeks
Evaluate preliminary efficacy of Toca 511 and Toca FC by assessing overall survival, and tumor response rates.
Measured: Overall survival, Overall survival at 6 months (OS6), 9 months (OS9), and 12 months (OS12)
Evaluate preliminary efficacy by assessing landmark PFS [6 months]
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2013 (estimated)
- Study startFeb 2014
- Primary completion3 Mar 2016
- Study completion3 Mar 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tocagen Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Asha Das, MD, Study director, Tocagen Inc.Steven Kalkanis, MD, Principal investigator, Henry Ford Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01985256
- Sponsor's protocol ID
- Tg 511-13-01
- Status last verified
- May 2018
- First submitted
- 8 Nov 2013
- 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
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01985256
- Acronym / sponsor ID
- Tg 511-13-01
- Conditions
- Glioblastoma Multiforme, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma, Anaplastic Oligoastrocytoma
- Keywords
- glioma, glioblastoma, glioblastoma multiforme, Grade IV astrocytoma, brain cancer, recurrent glioblastoma, GBM, AA
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Tocagen Inc.Industry (pharma, biotech, devices)
- Study start
- Feb 2014 (actual)
- Primary completion
- 3 Mar 2016 (actual)
- Study completion
- 3 Mar 2016 (actual)
- First posted
- 15 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Biological: Toca 511, Drug: Toca FCToca 511 vector/Toca FC |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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?
Key exclusion criteria (10 listed)
- 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?
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Toca 511Also: vocimagene amiretrorepvec, retroviral replicating vector (RRV)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. | Biological | Single Arm |
| Toca FCAlso: flucytosine, 5-FC, 5-FC XR, Toca FC | Drug | Single Arm |
Primary outcome
Maximum feasible, safe, and tolerated dose of Toca 511 as measured by dose limiting toxicities.
Time frame: 32 weeks
5 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2018.
- Background: PubMed 22070930Ostertag 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Asha Das, MD study director
Tocagen Inc.
Steven Kalkanis, MD principal investigator
Henry Ford Hospital
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Toca 511 and Toca FC in people with Glioblastoma Multiforme and Anaplastic Astrocytoma, run by Tocagen Inc. at 6 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 18 inclusion and 10 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 6 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?
Maximum feasible, safe, and tolerated dose of Toca 511 as measured by dose limiting toxicities. (time frame: 32 weeks). 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 NCT01985256, which also lists 1 linked publication.
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.