HIGH GRADE GLIOMAPhase 2NCT01403610
Safety and Efficacy Study of TH-302 CNS Penetration in Recurrent High Grade Astrocytoma Following Bevacizumab
A Phase 2 study testing TH-302 preoperative and TH-302 (escalating) with bevacizumab 10mg/kg in people with HIGH GRADE GLIOMA, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
Trial summary
The Primary Objectives are: To determine the extent by which TH-302 is able to penetrate the blood brain barrier and affect tumor tissue To assess the safety of single dose TH-302 in patients with high grade glioma undergoing surgery To assess the safety of TH-302 in combination with bevacizumab for patients with high… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIGH GRADE GLIOMA
- What is being tested?
- TH-302 preoperative and TH-302 (escalating) with bevacizumab 10mg/kg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2011to Oct 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At least 18 years of age
- Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's IRB/Ethics Committee
- Histologically confirmed high grade astrocytoma
- Progression following both standard combined modality treatment with radiation and temozolomide chemotherapy, as well as anti-angiogenic therapy (ie, bevacizumab)
- Recovered from toxicities of prior therapy to grade 0 or 1
- ECOG performance status of 0 or 1
Show all 11Show fewer
- Life expectancy of at least 3 months
- Acceptable liver function
- Acceptable renal function
- Acceptable hematologic status
- All women of childbearing potential must have a negative serum pregnancy test and male and female subjects must agree to use effective means of contraception (surgical sterilization or the use or barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel or an IUD) with their partner from entry into the study through 6 months after the last dose
Who cannot join
- The subject is receiving warfarin (or other coumarin derivatives) and is unable to switch to low molecular weight heparin (LMWH) before the first dose of study drug.
- The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or computerized tomography (CT) scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible.
- The subject is unable to undergo MRI scan (eg, has pacemaker).
- The subject has received enzyme-inducing anti-epileptic agents within 14 days of study drug (eg, carbamazepine, phenytoin, phenobarbital, primidone).
- The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 Grade ≤ 1 from AEs (except alopecia, anemia and lymphopenia) due to surgery, antineoplastic agents, investigational drugs, or other medications that were administered prior to study drug.
- The subject has evidence of wound dehiscence
Show all 18Show fewer
- Severe chronic obstructive or other pulmonary disease with hypoxemia (requires supplementary oxygen, symptoms due to hypoxemia or oxygen saturation <90% by pulse oximetry after a 2 minute walk) or in the opinion of the investigator any physiological state likely to cause normal tissue hypoxia
- The subject is pregnant or breast-feeding.
- The subject has serious intercurrent illness
- The subject has inherited bleeding diathesis or coagulopathy with the risk of bleeding.
- The subject has received any of the following prior anticancer therapy:
- Non-standard radiation therapy such as brachytherapy, systemic radioisotope therapy (RIT), or intra-operative radiotherapy (IORT). Note: stereotactic radiosurgery (SRS) is allowed
- Antiangiogenic agents whose primary mode of action is through the VEGF signaling within 21 days prior to first dose of study drug (surgical subjects only)
- Non-bevacizumab systemic therapy (including investigational agents and small-molecule kinase inhibitors) or non-cytotoxic hormonal therapy (eg, tamoxifen) within 7 days or 5 half-lives, whichever is shorter, prior first dose of study drug
- Biologic agents (antibodies, immune modulators, vaccines, cytokines) within 21 days prior to first dose of study drug
- Nitrosoureas or mitomycin C within 42 days, or metronomic/protracted low-dose chemotherapy within 14 days, or other cytotoxic chemotherapy within 28 days, prior to first dose of study drug
- Prior treatment with carmustine wafers
- Prior treatment with TH-302
Trial locations and contacts
1 site in 1 country.
United States1 site
Cancer Therapy & Research Center at UTHSCSA
San Antonio, Texas, 78229
About this study
Official title: A Phase 2, Investigator Initiated Study to Determine the Safety, Efficacy and CNS Penetration of TH-302 in Recurrent High Grade Astrocytoma Following Bevacizumab
The Primary Objectives are:
- To determine the extent by which TH-302 is able to penetrate the blood brain barrier and affect tumor tissue
- To assess the safety of single dose TH-302 in patients with high grade glioma undergoing surgery
- To assess the safety of TH-302 in combination with bevacizumab for patients with high grade glioma
- To determine the MTD and DLT(s) of TH-302 in combination with bevacizumab
The Secondary Objectives are:
To determine the progression-free survival with or without debulking craniotomy for patients treated with combination bevacizumab and TH-302 following recurrence on single agent bevacizumab
Read the detailed description
Single center, dose-escalation, prospective study with TH-302 single dose at 575 mg/m2 or placebo administered preoperatively, followed by postoperative combination therapy bevacizumab at 10mg/kg every 2 weeks and TH-302 at 240 - 670 mg/m2 every 2 weeks (4 week cycle) until disease progression. Subjects will be randomized (2:1) to receive pre-operative dose of TH-302 (surgical subjects only). Subjects not receiving surgery will receive combination therapy of bevacizumab at 10 mg/kg every 2 weeks and TH-302 at 240-670 mg/m2 every 2 weeks (4 week cycle) starting from Cycle 1, Day 1 until disease progression.
This study will use a classic dose escalation design to determine the MTD of TH-302 when used in combination with bevacizumab. The dose of TH-302 will be escalated in cohorts of 3-6 subjects. The initial dose of TH-302 will be 240 mg/m2. A dose level minus 1 will be built into the study in the event that subjects experience excessive toxicity at Dose Level 1. Dose escalation will continue to 340 mg/m2 and 670 mg/m2.
- Conditions
- HIGH GRADE GLIOMA
- Being tested
- TH-302 preoperative, Placebo, TH-302 (escalating) with bevacizumab 10mg/kg
- Keywords
- TH-302, Bevacizumab, Phase 2, Glioma, High Grade Glioma, CNS
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TH-302 preoperativeDrug
Also called Study drug
TH-302 single dose at 575 mg/m2 administered preoperatively, followed by postoperative combination therapy bevacizumab at 10mg/kg every 2 weeks and TH-302 at 240 - 480 mg/m2 every 2 weeks (4 week cycle) until disease progression. Subjects will be randomized (2:1) to receive pre-operative dose of TH-302.
PlaceboDrug
Also called Study placebo
Placebo administered preoperatively, followed by postoperative combination therapy bevacizumab at 10mg/kg every 2 weeks and TH-302 at 240 - 480 mg/m2 every 2 weeks (4 week cycle) until disease progression. Subjects will be randomized (2:1) to receive pre-operative dose of TH-302.
TH-302 (escalating) with bevacizumab 10mg/kgDrug
Also called Study drug escalating dose
Combination of 10mg/m2 of bevacizumab with an escalating dose of TH-302 from 240 to 670 mg/m2
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Subjects received TH-302 single dose at 575 mg/m2 or placebo administered preoperative in a 2:1 randomization and were then administered 240 mg/m2 of TH-302 post-operative. Receives: Drug: TH-302 preoperative; Drug: Placebo; Drug: TH-302 (escalating) with bevacizumab 10mg/kg |
| Cohort 2 | Experimental | Surgical subjects will receive TH-302 at 340 mg/m2 every 2 weeks (4 week cycles) starting after surgery from Cycle 1, Day 1 until disease progression. Receives: Drug: TH-302 preoperative; Drug: TH-302 (escalating) with bevacizumab 10mg/kg |
| Cohort 3 | Experimental | Surgical or Non-Surgical subjects will receive TH-302 at 480 mg/m2 every 2 weeks (4 week cycles) starting after surgery from Cycle 1, Day 1 until disease progression. Receives: Drug: TH-302 (escalating) with bevacizumab 10mg/kg |
| Cohort 4 | Experimental | Non-surgical subjects will receive a dose up to 670 mg/m2 of TH-302 Receives: Drug: TH-302 (escalating) with bevacizumab 10mg/kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Progression
Time from initiation study until radiographic progression by RANO criteria
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2011 (estimated)
- Study startJun 2011
- Primary completionOct 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIGH GRADE GLIOMAStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center at San AntonioThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andrew Brenner, MD,, Principal investigator, Institute for Drug Development
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01403610
- Sponsor's protocol ID
- CTRC 11-24
- Other IDs
- CTRC 11-24
- Status last verified
- Mar 2019
- First submitted
- 22 Jul 2011
- Last updated
- 24 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Investigator Initiated Study to Determine the Safety, Efficacy and CNS Penetration of TH-302 in Recurrent High Grade Astrocytoma Following Bevacizumab
- ClinicalTrials.gov ID
- NCT01403610
- Acronym / sponsor ID
- CTRC 11-24
- Conditions
- HIGH GRADE GLIOMA
- Keywords
- TH-302, Bevacizumab, Phase 2, Glioma, High Grade Glioma, CNS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Study start
- Jun 2011
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 27 Jul 2011 (estimated)
- Results
- Posted 24 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Primary Objectives are:
- To determine the extent by which TH-302 is able to penetrate the blood brain barrier and affect tumor tissue
- To assess the safety of single dose TH-302 in patients with high grade glioma undergoing surgery
- To assess the safety of TH-302 in combination with bevacizumab for patients with high grade glioma
- To determine the MTD and DLT(s) of TH-302 in combination with bevacizumab
The Secondary Objectives are:
To determine the progression-free survival with or without debulking craniotomy for patients treated with combination bevacizumab and TH-302 following recurrence on single agent bevacizumab
Detailed description
Single center, dose-escalation, prospective study with TH-302 single dose at 575 mg/m2 or placebo administered preoperatively, followed by postoperative combination therapy bevacizumab at 10mg/kg every 2 weeks and TH-302 at 240 - 670 mg/m2 every 2 weeks (4 week cycle) until disease progression. Subjects will be randomized (2:1) to receive pre-operative dose of TH-302 (surgical subjects only). Subjects not receiving surgery will receive combination therapy of bevacizumab at 10 mg/kg every 2 weeks and TH-302 at 240-670 mg/m2 every 2 weeks (4 week cycle) starting from Cycle 1, Day 1 until disease progression.
This study will use a classic dose escalation design to determine the MTD of TH-302 when used in combination with bevacizumab. The dose of TH-302 will be escalated in cohorts of 3-6 subjects. The initial dose of TH-302 will be 240 mg/m2. A dose level minus 1 will be built into the study in the event that subjects experience excessive toxicity at Dose Level 1. Dose escalation will continue to 340 mg/m2 and 670 mg/m2.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: TH-302 preoperative, Drug: Placebo, Drug: TH-302 (escalating) with bevacizumab 10mg/kgSubjects received TH-302 single dose at 575 mg/m2 or placebo administered preoperative in a 2:1 randomization and were then administered 240 mg/m2 of TH-302 post-operative. |
| Cohort 2 | Experimental | Drug: TH-302 preoperative, Drug: TH-302 (escalating) with bevacizumab 10mg/kgSurgical subjects will receive TH-302 at 340 mg/m2 every 2 weeks (4 week cycles) starting after surgery from Cycle 1, Day 1 until disease progression. |
| Cohort 3 | Experimental | Drug: TH-302 (escalating) with bevacizumab 10mg/kgSurgical or Non-Surgical subjects will receive TH-302 at 480 mg/m2 every 2 weeks (4 week cycles) starting after surgery from Cycle 1, Day 1 until disease progression. |
| Cohort 4 | Experimental | Drug: TH-302 (escalating) with bevacizumab 10mg/kgNon-surgical subjects will receive a dose up to 670 mg/m2 of TH-302 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- At least 18 years of age
- Ability to understand the purposes and risks of the study and has signed a written informed consent form approved by the investigator's IRB/Ethics Committee
- Histologically confirmed high grade astrocytoma
- Progression following both standard combined modality treatment with radiation and temozolomide chemotherapy, as well as anti-angiogenic therapy (ie, bevacizumab)
- Recovered from toxicities of prior therapy to grade 0 or 1
Key exclusion criteria (18 listed)
- The subject is receiving warfarin (or other coumarin derivatives) and is unable to switch to low molecular weight heparin (LMWH) before the first dose of study drug.
- The subject has evidence of acute intracranial or intratumoral hemorrhage either by MRI or computerized tomography (CT) scan. Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin are eligible.
- The subject is unable to undergo MRI scan (eg, has pacemaker).
- The subject has received enzyme-inducing anti-epileptic agents within 14 days of study drug (eg, carbamazepine, phenytoin, phenobarbital, primidone).
- The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 Grade ≤ 1 from AEs (except alopecia, anemia and lymphopenia) due to surgery, antineoplastic agents, investigational drugs, or other medications that were administered prior to study drug.
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 |
|---|---|---|
| TH-302 preoperativeAlso: Study drugTH-302 single dose at 575 mg/m2 administered preoperatively, followed by postoperative combination therapy bevacizumab at 10mg/kg every 2 weeks and TH-302 at 240 - 480 mg/m2 every 2 weeks (4 week cycle) until disease progression. Subjects will be randomized (2:1) to receive pre-operative dose of TH-302. | Drug | Cohort 1, Cohort 2 |
| PlaceboAlso: Study placeboPlacebo administered preoperatively, followed by postoperative combination therapy bevacizumab at 10mg/kg every 2 weeks and TH-302 at 240 - 480 mg/m2 every 2 weeks (4 week cycle) until disease progression. Subjects will be randomized (2:1) to receive pre-operative dose of TH-302. | Drug | Cohort 1 |
| TH-302 (escalating) with bevacizumab 10mg/kgAlso: Study drug escalating doseCombination of 10mg/m2 of bevacizumab with an escalating dose of TH-302 from 240 to 670 mg/m2 | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
Primary outcome
Time to Progression
Time frame: 2 years
Time from initiation study until radiographic progression by RANO criteria
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for HIGH GRADE GLIOMA
RecruitingPhase 1
A Phase 1 Safety and Dose Finding Study of GLIX1 in Adults With Recurrent or Progressive High-grade Glioma
Glioblastoma Multiforme of Brain, Glioma
RecruitingEarly Phase 1
Intratumoral Extracellular Metabolic Impact of DFMO and AMXT 1501 in Patients With Diffuse or High Grade Glioma
Diffuse Glioma, Malignant Glioma
Active, not recruitingPhase 1
Genetically Modified T-cells in Treating Patients With Recurrent or Refractory Malignant Glioma
Recurrent Glioblastoma, Recurrent Malignant Glioma
Active, not recruitingPhase 1/2
A Study of the Drug Selinexor With Radiation Therapy in Patients With Newly-Diagnosed Diffuse Intrinsic Pontine (DIPG) Glioma and High-Grade Glioma (HGG)
Malignant Glioma
RecruitingPhase 1
Multiple Intracerebral Doses of Neural Stem Cell-Based Virotherapy (NSC-CRAd-S-pk7) for the Treatment of Recurrent High-Grade Gliomas
Currently Only Enrolling Glioblastoma Patients at First Recurrence
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.
Andrew Brenner, MD, principal investigator
Institute for Drug Development
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TH-302 preoperative and TH-302 (escalating) with bevacizumab 10mg/kg in people with HIGH GRADE GLIOMA, run by The University of Texas Health Science Center at San Antonio at 1 site 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 11 inclusion and 18 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 24 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Time to Progression (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Jul 2019.