Glioblastoma MultiformePhase 1/2NCT01933815
Dose-Escalation Study of TPI 287 + Avastin Followed by Randomized Study of the Same Versus Avastin for Glioblastoma
A Phase 1/2 study testing TPI 287 and Bevacizumab in people with Glioblastoma Multiforme, run by Cortice Biosciences, Inc. at 9 sites in United States.
Trial summary
This trial is divided into two parts, a dose-escalation study (phase 1) and a randomized study (phase 2). The purpose of the dose-escalation study (phase 1) is to determine the safety, maximum tolerated dose (MTD), and efficacy of TPI 287 in combination with Avastin (bevacizumab) in subjects who have glioblastoma… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- TPI 287 and Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 9 sitesUnited States
- Study dates
- Aug 2013to May 2025
- Phase
- Phase 1/2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically proven GBM
- Disease progression following radiation and TMZ
- Up to 2 prior relapses allowed
- Baseline MRI within 17 days of Day 1 \& on steroid dosage that has been stable or decreasing for at least 5 days
- Recent resection of recurrent or progressive tumor allowed as long as at least 4 weeks have elapsed from date of surgery and the subject has recovered from surgery
- Life expectancy >12 weeks
Show all 19Show fewer
- Eighteen years old or older
- KPS equal to or greater than 70
- Recovered from toxic effects of prior therapy to < Grade 2 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) prior to Day 1. Minimum duration required between prior therapy and Day 1 is:
- At least 12 weeks from completion of radiation therapy except if there is unequivocal evidence for tumor recurrence in which case at least 4 weeks
- 4 weeks from prior cytotoxic therapy
- 4 weeks from prior experimental drug
- 6 weeks from nitrosoureas
- 3 weeks from procarbazine
- 1 week for non-cytotoxic agents, such as interferon, tamoxifen, \& cis-retinoic acid
- Adequate bone marrow function (absolute neutrophil count > 1,500/mm3 and platelet count of > 100,000/mm3), adequate liver function [ALT and AST <3 x upper limit normal (ULN), alkaline phosphatase <2 x ULN, and total bilirubin <1.5 mg/dL], \& adequate renal function (BUN and creatinine <1.5 x ULN)
- Minimum hemoglobin of 9 g/dL
- Males \& women of childbearing potential must agree to abstain from sex or use an adequate method of contraception for the duration of study, \& for 6 months after last dose of study drug
- Signed \& dated informed consent prior to Screening evaluations
Who cannot join
- Radiographic evidence of contrast-enhancing tumor crossing midline, leptomeningeal dissemination, gliomatosis cerebri or infratentorial tumor
- Evidence or suspicion of disease metastatic to sites remote from the supratentorial brain
- Prior treatment with bevacizumab or other anti-vascular endothelial growth factor (VEGF) drugs
- Prior treatment with tyrosine-kinase inhibitors targeting VEGF, platelet-derived growth factor, fibroblast growth factor, tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2 (TIE-2), or angiopoietin (or their receptors)
- Prior treatment with histone deacetylase inhibitors or mammalian target of rapamycin (mTOR) inhibitors
- Prior treatment with TPI 287
Show all 33Show fewer
- Treatment with Enzyme-Inducing Anti-Epileptic Drugs within 2 weeks prior to Day 1
- Treatment with drugs or herbal supplements known to be strong inhibitors/inducers of cytochrome P450 3A4 or cytochrome P450 2C8 within 2 weeks prior to Day 1
- Received more than one course of radiation therapy or more than a total dose of 65 Gy. May have received radiosurgery as part of initial therapy; however, the dose counts against the total dose limit.
- Prior taxane, vincristine, or other microtubule inhibitor chemotherapies for treatment of GBM or other malignancy
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to Day 1
- Any condition, including the presence of clinically significant laboratory abnormalities, which places subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study, including:
- Active infection including known AIDS or Hepatitis C or with a fever ≥38.5°C within 3 days prior to enrollment
- Diseases or conditions that obscure toxicity or dangerously alter drug metabolism
- Serious intercurrent medical illness (e.g., symptomatic congestive heart failure)
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from providing informed consent
- Inadequately controlled hypertension (defined as systolic blood pressure >140 mmHg and/or diastolic blood pressure > 90 mmHg)
- Prior history of hypertensive crisis or hypertensive encephalopathy
- New York Heart Association Grade II or greater congestive heart failure
- History of myocardial infarction or unstable angina within 6 months prior to Day 1
- History of stroke or transient ischemic attack within 6 months prior to Day1
- Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1
- History of hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1
- Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
- Grade 2 or higher peripheral neuropathy per NCI CTCAE
- History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
- Serious, non-healing wound, active ulcer, or untreated bone fracture
- Proteinuria at Screening. Subjects with a urine dipstick protein ≥2+ at Screening should undergo a 24-hour urine collection and must demonstrate ≤1g of protein in 24 hours to be eligible
- Known hypersensitivity to inactive ingredient of bevacizumab
- Known hypersensitivity to inactive ingredient of TPI 287
- Pregnancy or lactation
- Inability to comply with protocol
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35249
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
The Long Island Brain Tumor Center at Neurological Surgery, P.C.
Commack, New York, 11725
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
Memorial Hermann Hospital
Houston, Texas, 77030
The Long Island Brain Tumor Center at Neurological Surgery, P.C.
Lake Success, New York, 11042
University of Rochester Medical Center
Rochester, New York, 14642
Swedish Neuroscience Institute
Seattle, Washington, 98122
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Phase 1/2 Dose-Escalation Study of TPI 287 in Combination With Bevacizumab Followed by Randomized Study of the Maximum Tolerated Dose of TPI 287 in Combination With Bevacizumab Versus Bevacizumab Alone in Adults With Recurrent Glioblastoma
This trial is divided into two parts, a dose-escalation study (phase 1) and a randomized study (phase 2).
The purpose of the dose-escalation study (phase 1) is to determine the safety, maximum tolerated dose (MTD), and efficacy of TPI 287 in combination with Avastin (bevacizumab) in subjects who have glioblastoma multiforme (GBM) that has progressed following prior radiation therapy and temozolomide (TMZ).
The purpose of the randomized study (phase 2) is to determine the safety and efficacy of the phase 1 MTD of TPI 287 in combination with bevacizumab versus bevacizumab alone in subjects who have GBM that has progressed following prior radiation therapy and TMZ.
Read the detailed description
This multi-center trial is a phase 1/2 study that will be conducted in two sequential phases, phase 1 and phase 2.
Phase 1 of the trial is a dose-escalation study of the safety, tolerability (MTD), and efficacy of TPI 287 in combination with bevacizumab in subjects who have GBM that has progressed following prior radiation therapy and TMZ.
- All subjects will be administered TPI 287 as an intravenous (IV) infusion (target duration of 1 hour) once every 3 weeks (Days 1 and 22 of a 42-day cycle) and bevacizumab as a 30 to 90 minute IV infusion once every 2 weeks (Days 1, 15, and 29 of the 42-day cycle). The subsequent cycle will start 3 weeks after the last TPI 287 infusion and 2 weeks after the last bevacizumab infusion, maintaining the once every 3 week and once every 2 week schedule, respectively.
- The dose of TPI 287 will be escalated in sequential dose cohorts of 3 to 6 subjects, while the dose of bevacizumab remains constant (10 mg/kg). The initial cohort of 3 subjects will be treated at a TPI 287 dose of 140 mg/m2. The next four dose levels will be 150, 160, 170, and 180 mg/m2. Dose levels beyond 180 mg/m2 will be increased in increments of 20 mg/m2 (i.e., 200, 220, 240 mg/m2, etc.).
- Once a dose level is identified that exceeds the MTD, dose de-escalation will be used to further refine the MTD. Specifically, 3 subjects will be treated at an intermediate dose level, halfway between the dose level that exceeded the MTD and the dose level immediately prior (e.g., 230 mg/m2, if 240 mg/m2 exceeded the MTD).
- Subjects will be assigned to dose cohorts in the order that they are enrolled; there is no randomization for phase 1. Approximately 20 to 32 subjects are planned for enrollment in phase 1, depending on the dose level at which dose limiting toxicities (DLTs) are observed.
- Dose modifications and delays will be required as described in the protocol. Subjects may continue on treatment unless they meet one or more of the discontinuation criteria outlined in the protocol. Subjects who are discontinued prior to completing Cycle 1 for any reason other than toxicity will be replaced.
- Adverse events (AEs) and concomitant medications will be monitored throughout the study. Subjects will be given a diary to record any AEs or concomitant medications taken between visits. Additional safety evaluations will include physical examination (including neurologic examination), Karnofsky performance status (KPS), weight (body surface area, BSA), vital signs, hematology, serum chemistry, and urinalysis.
- Efficacy evaluations will include magnetic resonance imaging [MRI, including both pre and post-gadolinium T1-weighted scans and T2/fluid attenuated inversion recovery (FLAIR) images], corticosteroid usage, and neurologic status (as measured by neurologic exam and KPS).
Phase 2 of the trial is a randomized study of the safety and efficacy of the phase 1 MTD of TPI 287 in combination with bevacizumab versus bevacizumab alone in subjects who have GBM that has progressed following prior radiation therapy and TMZ.
- Sixty subjects will be randomized 1:1 to receive either TPI 287 in combination with bevacizumab or bevacizumab alone.
- For the combination arm, the subjects will be administered TPI 287 as an IV infusion (target duration of 1 hour) once every 3 weeks (Days 1 and 22 of a 42-day cycle) and bevacizumab as a 30 to 90 minute IV infusion once every 2 weeks (Days 1, 15, and 29 of the 42-day cycle). The dose of TPI 287 will be the MTD determined in phase 1, and the dose of bevacizumab will be the same as phase 1 (10 mg/kg).
- Subjects randomized to the bevacizumab alone arm will be administered 10 mg/kg bevacizumab as a 30 to 90 minute IV infusion once every 2 weeks (Days 1, 15, and 29 of the 42-day cycle).
- The same dose modifications and delays required in phase 1 will apply to phase 2. Subjects may continue on treatment unless they meet one or more of the discontinuation criteria outlined in the protocol. There will be no subject replacement for phase 2 of the trial.
- The safety and efficacy evaluations during phase 2 will be the same as those in phase 1. In addition, subjects participating in phase 2 will be telephoned every two months following the final study visit (4 weeks after the last dose of study drug) for up to two years after randomization to follow survival.
- Subjects that participate in phase 1 of the trial will not be eligible to participate in phase 2 of the trial.
- Conditions
- Glioblastoma Multiforme
- Being tested
- TPI 287, Bevacizumab
- Keywords
- Glioblastoma multiforme, Glioblastoma, Radiotherapy, Temozolomide, TPI 287, Taxoid, Avastin, Bevacizumab
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TPI 287Drug
Also called TPI-287, NBT 287
TPI 287 is a microtubule inhibitor belonging to the taxane diterpenoid (taxoid) family, and specifically to the abeotaxane class. TPI 287 is an Investigational Drug.
BevacizumabDrug
Also called Avastin
Avastin (bevacizumab) is an FDA approved drug indicated for multiple cancers, including as a single agent for GBM for adult patients with progressive disease following prior therapy. Single agent effectiveness is based on improvement in objective response rate; no data is available demonstrating improvement in disease-related symptoms or survival with bevacizumab.
| Study group | Role | What they receive |
|---|---|---|
| TPI 287 + bevacizumab | Experimental | All subjects in phase 1 \& subjects randomized to the TPI 287 + bevacizumab arm in phase 2 will be administered a 1-hour IV infusion of TPI 287 once every 3 weeks (Days 1 \& 22 of 42-day cycle) \& a 30-90 minute IV infusion of bevacizumab once every 2 weeks (Days 1, 15, \& 29).
In phase 1, the dose of TPI 287 will be escalated in sequential dose cohorts of 3 to 6, while the dose of bevacizumab remains constant (10 mg/kg). The first 5 dose levels will be 140, 150, 160, 170, \& 180 mg/m2. Dose levels beyond 180 mg/m2 will be increased in increments of 20 mg/m2. Three subjects will be treated at a dose level halfway between the dose level that exceeds the MTD and the dose level immediately prior to further refine the MTD.
In phase 2, the dose of TPI 287 will be the MTD determined in phase 1, \& the dose of bevacizumab will be the same as phase 1 (10 mg/kg).
Subjects may continue on treatment unless they meet one or more of the protocol discontinuation criteria. Receives: Drug: TPI 287; Drug: Bevacizumab |
| Bevacizumab | Active comparator | All subjects randomized to the bevacizumab alone arm in phase 2 will be administered bevacizumab as a 30 to 90 minute IV infusion once every 2 weeks (Days 1, 15, and 29 of a 42-day cycle). The dose of bevacizumab will be 10 mg/kg.
Subjects will be withdrawn from the study if they meet one or more of the discontinuation criteria outlined in the protocol; however, treatment with bevacizumab may continue under the FDA approved labeling for bevacizumab at the discretion of the subject's doctor.
All subjects in phase 1 will be administered TPI 287 in combination with bevacizumab (i.e., there will be no bevacizumab alone arm during phase 1). Receives: Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Safety of TPI 287 + bevacizumab in adults with GBM that progressed following radiation & TMZ as measured by AEs, physical/neurologic exam, KPS, weight, vital signs, hematology, serum chemistry, & urinalysis
Measured: Continuously over study treatment through 4 weeks after last dose of study drug
Phase 1: MTD of TPI 287 + bevacizumab in adults with GBM that progressed following radiation & TMZ
The MTD will be defined as the highest dose level achieved at which no more than 1 out of 6 subjects experienced a DLT that initiated within 42 days of receiving the first dose of study drug.
Measured: Within 42 days of receiving the first dose of study drug
Phase 2: Efficacy of phase 1 MTD of TPI 287 + bevacizumab versus bevacizumab alone in adults with GBM that progressed following radiation and TMZ as measured by median PFS
The Response Assessment in Neuro-Oncology (RANO) working group recommendations for updated response criteria for high-grade gliomas (Wen et al. 2010) will be used to determine response for this trial.
Measured: Baseline & on Day 1 of each 42-day treatment cycle starting with Cycle 2, and/or as clinically indicated
Secondary outcomes (3)
Phase 1: Efficacy of TPI 287 + bevacizumab in adults with GBM that progressed following radiation and TMZ as measured by median progression free survival (PFS), overall response rate, & progression free survival rate at 4 & 6 months (PFS4 & PFS6)
Measured: Baseline & on Day 1 of each 42-day treatment cycle starting with Cycle 2, and/or as clinically indicated
Phase 2: Safety of TPI 287 + bevacizumab versus bevacizumab alone in adults with GBM that progressed following radiation & TMZ as measured by AEs, physical/neurologic exam, KPS, weight, vital signs, hematology, serum chemistry, & urinalysis
Measured: Continuously over study treatment through 4 weeks after last dose of study drug
Phase 2: Efficacy of phase 1 MTD of TPI 287 + bevacizumab versus bevacizumab alone in adults with GBM that progressed following radiation and TMZ as measured by overall survival and overall response rate
Measured: Overall response rate: baseline & on Day 1 of each 42-day treatment cycle starting with Cycle 2, and/or as clinically indicated; overall survival: up to two years after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2013 (estimated)
- Study startAug 2013
- Primary completionNov 2024 (estimated)
- Study completionMay 2025 (estimated)
Why it stopped: Business reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 92 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cortice Biosciences, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- J. P. Duic, M.D., Principal investigator, The Long Island Brain Tumor Center at Neurological Surgery, P.C.Samuel A. Goldlust, M.D., Principal investigator, John Theurer Cancer Center at Hackensack University Medical CenterLouis B. Nabors, III, M.D., Principal investigator, University of Alabama at BirminghamSigmund Hsu, M.D., Principal investigator, Memorial Hermann HospitalNimish Mohile, M.D., Principal investigator, University of RochesterTara L. Benkers, M.D., Principal investigator, Swedish Neuroscience InstituteJian Campian, M.D., Principal investigator, Washington University School of MedicinePierre Giglio, M.D., Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01933815
- Sponsor's protocol ID
- TPI-287-17
- Status last verified
- Jul 2022
- First submitted
- 26 Aug 2013
- Last updated
- 22 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2 Dose-Escalation Study of TPI 287 in Combination With Bevacizumab Followed by Randomized Study of the Maximum Tolerated Dose of TPI 287 in Combination With Bevacizumab Versus Bevacizumab Alone in Adults With Recurrent Glioblastoma
- ClinicalTrials.gov ID
- NCT01933815
- Acronym / sponsor ID
- TPI-287-17
- Conditions
- Glioblastoma Multiforme
- Keywords
- Glioblastoma multiforme, Glioblastoma, Radiotherapy, Temozolomide, TPI 287, Taxoid, Avastin, Bevacizumab
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: Business reasons
- Enrolment
- 92 participants (estimated)
- Lead sponsor
- Cortice Biosciences, Inc.Industry (pharma, biotech, devices)
- Study start
- Aug 2013 (actual)
- Primary completion
- Nov 2024 (estimated)
- Study completion
- May 2025 (estimated)
- First posted
- 2 Sep 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 trial is divided into two parts, a dose-escalation study (phase 1) and a randomized study (phase 2).
The purpose of the dose-escalation study (phase 1) is to determine the safety, maximum tolerated dose (MTD), and efficacy of TPI 287 in combination with Avastin (bevacizumab) in subjects who have glioblastoma multiforme (GBM) that has progressed following prior radiation therapy and temozolomide (TMZ).
The purpose of the randomized study (phase 2) is to determine the safety and efficacy of the phase 1 MTD of TPI 287 in combination with bevacizumab versus bevacizumab alone in subjects who have GBM that has progressed following prior radiation therapy and TMZ.
Detailed description
This multi-center trial is a phase 1/2 study that will be conducted in two sequential phases, phase 1 and phase 2.
Phase 1 of the trial is a dose-escalation study of the safety, tolerability (MTD), and efficacy of TPI 287 in combination with bevacizumab in subjects who have GBM that has progressed following prior radiation therapy and TMZ.
- All subjects will be administered TPI 287 as an intravenous (IV) infusion (target duration of 1 hour) once every 3 weeks (Days 1 and 22 of a 42-day cycle) and bevacizumab as a 30 to 90 minute IV infusion once every 2 weeks (Days 1, 15, and 29 of the 42-day cycle). The subsequent cycle will start 3 weeks after the last TPI 287 infusion and 2 weeks after the last bevacizumab infusion, maintaining the once every 3 week and once every 2 week schedule, respectively.
- The dose of TPI 287 will be escalated in sequential dose cohorts of 3 to 6 subjects, while the dose of bevacizumab remains constant (10 mg/kg). The initial cohort of 3 subjects will be treated at a TPI 287 dose of 140 mg/m2. The next four dose levels will be 150, 160, 170, and 180 mg/m2. Dose levels beyond 180 mg/m2 will be increased in increments of 20 mg/m2 (i.e., 200, 220, 240 mg/m2, etc.).
- Once a dose level is identified that exceeds the MTD, dose de-escalation will be used to further refine the MTD. Specifically, 3 subjects will be treated at an intermediate dose level, halfway between the dose level that exceeded the MTD and the dose level immediately prior (e.g., 230 mg/m2, if 240 mg/m2 exceeded the MTD).
- Subjects will be assigned to dose cohorts in the order that they are enrolled; there is no randomization for phase 1. Approximately 20 to 32 subjects are planned for enrollment in phase 1, depending on the dose level at which dose limiting toxicities (DLTs) are observed.
- Dose modifications and delays will be required as described in the protocol. Subjects may continue on treatment unless they meet one or more of the discontinuation criteria outlined in the protocol. Subjects who are discontinued prior to completing Cycle 1 for any reason other than toxicity will be replaced.
- Adverse events (AEs) and concomitant medications will be monitored throughout the study. Subjects will be given a diary to record any AEs or concomitant medications taken between visits. Additional safety evaluations will include physical examination (including neurologic examination), Karnofsky performance status (KPS), weight (body surface area, BSA), vital signs, hematology, serum chemistry, and urinalysis.
- Efficacy evaluations will include magnetic resonance imaging [MRI, including both pre and post-gadolinium T1-weighted scans and T2/fluid attenuated inversion recovery (FLAIR) images], corticosteroid usage, and neurologic status (as measured by neurologic exam and KPS).
Phase 2 of the trial is a randomized study of the safety and efficacy of the phase 1 MTD of TPI 287 in combination with bevacizumab versus bevacizumab alone in subjects who have GBM that has progressed following prior radiation therapy and TMZ.
- Sixty subjects will be randomized 1:1 to receive either TPI 287 in combination with bevacizumab or bevacizumab alone.
- For the combination arm, the subjects will be administered TPI 287 as an IV infusion (target duration of 1 hour) once every 3 weeks (Days 1 and 22 of a 42-day cycle) and bevacizumab as a 30 to 90 minute IV infusion once every 2 weeks (Days 1, 15, and 29 of the 42-day cycle). The dose of TPI 287 will be the MTD determined in phase 1, and the dose of bevacizumab will be the same as phase 1 (10 mg/kg).
- Subjects randomized to the bevacizumab alone arm will be administered 10 mg/kg bevacizumab as a 30 to 90 minute IV infusion once every 2 weeks (Days 1, 15, and 29 of the 42-day cycle).
- The same dose modifications and delays required in phase 1 will apply to phase 2. Subjects may continue on treatment unless they meet one or more of the discontinuation criteria outlined in the protocol. There will be no subject replacement for phase 2 of the trial.
- The safety and efficacy evaluations during phase 2 will be the same as those in phase 1. In addition, subjects participating in phase 2 will be telephoned every two months following the final study visit (4 weeks after the last dose of study drug) for up to two years after randomization to follow survival.
- Subjects that participate in phase 1 of the trial will not be eligible to participate in phase 2 of the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TPI 287 + bevacizumab | Experimental | Drug: TPI 287, Drug: BevacizumabAll subjects in phase 1 \& subjects randomized to the TPI 287 + bevacizumab arm in phase 2 will be administered a 1-hour IV infusion of TPI 287 once every 3 weeks (Days 1 \& 22 of 42-day cycle) \& a 30-90 minute IV infusion of bevacizumab once every 2 weeks (Days 1, 15, \& 29). In phase 1, the dose of TPI 287 will be escalated in sequential dose cohorts of 3 to 6, while the dose of bevacizumab remains constant (10 mg/kg). The first 5 dose levels will be 140, 150, 160, 170, \& 180 mg/m2. Dose levels beyond 180 mg/m2 will be increased in increments of 20 mg/m2. Three subjects will be treated at a dose level halfway between the dose level that exceeds the MTD and the dose level immediately prior to further refine the MTD. In phase 2, the dose of TPI 287 will be the MTD determined in phase 1, \& the dose of bevacizumab will be the same as phase 1 (10 mg/kg). Subjects may continue on treatment unless they meet one or more of the protocol discontinuation criteria. |
| Bevacizumab | Active comparator | Drug: BevacizumabAll subjects randomized to the bevacizumab alone arm in phase 2 will be administered bevacizumab as a 30 to 90 minute IV infusion once every 2 weeks (Days 1, 15, and 29 of a 42-day cycle). The dose of bevacizumab will be 10 mg/kg. Subjects will be withdrawn from the study if they meet one or more of the discontinuation criteria outlined in the protocol; however, treatment with bevacizumab may continue under the FDA approved labeling for bevacizumab at the discretion of the subject's doctor. All subjects in phase 1 will be administered TPI 287 in combination with bevacizumab (i.e., there will be no bevacizumab alone arm during phase 1). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Histologically proven GBM
- Disease progression following radiation and TMZ
- Up to 2 prior relapses allowed
- Baseline MRI within 17 days of Day 1 \& on steroid dosage that has been stable or decreasing for at least 5 days
- Recent resection of recurrent or progressive tumor allowed as long as at least 4 weeks have elapsed from date of surgery and the subject has recovered from surgery
Key exclusion criteria (33 listed)
- Radiographic evidence of contrast-enhancing tumor crossing midline, leptomeningeal dissemination, gliomatosis cerebri or infratentorial tumor
- Evidence or suspicion of disease metastatic to sites remote from the supratentorial brain
- Prior treatment with bevacizumab or other anti-vascular endothelial growth factor (VEGF) drugs
- Prior treatment with tyrosine-kinase inhibitors targeting VEGF, platelet-derived growth factor, fibroblast growth factor, tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 2 (TIE-2), or angiopoietin (or their receptors)
- Prior treatment with histone deacetylase inhibitors or mammalian target of rapamycin (mTOR) inhibitors
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 |
|---|---|---|
| TPI 287Also: TPI-287, NBT 287TPI 287 is a microtubule inhibitor belonging to the taxane diterpenoid (taxoid) family, and specifically to the abeotaxane class. TPI 287 is an Investigational Drug. | Drug | TPI 287 + bevacizumab |
| BevacizumabAlso: AvastinAvastin (bevacizumab) is an FDA approved drug indicated for multiple cancers, including as a single agent for GBM for adult patients with progressive disease following prior therapy. Single agent effectiveness is based on improvement in objective response rate; no data is available demonstrating improvement in disease-related symptoms or survival with bevacizumab. | Drug | Bevacizumab, TPI 287 + bevacizumab |
Primary outcome
Phase 1: Safety of TPI 287 + bevacizumab in adults with GBM that progressed following radiation & TMZ as measured by AEs, physical/neurologic exam, KPS, weight, vital signs, hematology, serum chemistry, & urinalysis
Time frame: Continuously over study treatment through 4 weeks after last dose of study drug
Phase 1: MTD of TPI 287 + bevacizumab in adults with GBM that progressed following radiation & TMZ
Time frame: Within 42 days of receiving the first dose of study drug
The MTD will be defined as the highest dose level achieved at which no more than 1 out of 6 subjects experienced a DLT that initiated within 42 days of receiving the first dose of study drug.
Phase 2: Efficacy of phase 1 MTD of TPI 287 + bevacizumab versus bevacizumab alone in adults with GBM that progressed following radiation and TMZ as measured by median PFS
Time frame: Baseline & on Day 1 of each 42-day treatment cycle starting with Cycle 2, and/or as clinically indicated
The Response Assessment in Neuro-Oncology (RANO) working group recommendations for updated response criteria for high-grade gliomas (Wen et al. 2010) will be used to determine response for this trial.
3 secondary outcomes
Phase 1: Efficacy of TPI 287 + bevacizumab in adults with GBM that progressed following radiation and TMZ as measured by median progression free survival (PFS), overall response rate, & progression free survival rate at 4 & 6 months (PFS4 & PFS6)
Time frame: Baseline & on Day 1 of each 42-day treatment cycle starting with Cycle 2, and/or as clinically indicated
Phase 2: Safety of TPI 287 + bevacizumab versus bevacizumab alone in adults with GBM that progressed following radiation & TMZ as measured by AEs, physical/neurologic exam, KPS, weight, vital signs, hematology, serum chemistry, & urinalysis
Time frame: Continuously over study treatment through 4 weeks after last dose of study drug
Phase 2: Efficacy of phase 1 MTD of TPI 287 + bevacizumab versus bevacizumab alone in adults with GBM that progressed following radiation and TMZ as measured by overall survival and overall response rate
Time frame: Overall response rate: baseline & on Day 1 of each 42-day treatment cycle starting with Cycle 2, and/or as clinically indicated; overall survival: up to two years after randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2023.
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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.
J. P. Duic, M.D. principal investigator
The Long Island Brain Tumor Center at Neurological Surgery, P.C.
Samuel A. Goldlust, M.D. principal investigator
John Theurer Cancer Center at Hackensack University Medical Center
Louis B. Nabors, III, M.D. principal investigator
University of Alabama at Birmingham
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TPI 287 and Bevacizumab in people with Glioblastoma Multiforme, run by Cortice Biosciences, Inc. at 9 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 19 inclusion and 33 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: paused, as of the sponsor's last update on 22 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 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 combined 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.
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?
Results are not available in the source record.
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?
Phase 1: Safety of TPI 287 + bevacizumab in adults with GBM that progressed following radiation & TMZ as measured by AEs, physical/neurologic exam, KPS, weight, vital signs, hematology, serum chemistry, & urinalysis (time frame: Continuously over study treatment through 4 weeks after last dose of study drug). The study lists 3 primary outcomes in all. 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 22 Feb 2023.