Trial of Ponatinib in Patients With Bevacizumab-Refractory Glioblastoma

Completed · Phase 2

Conditions studied: Glioblastoma

In brief

This research study is studying a chemotherapy as a possible treatment for recurrent glioblastoma that has not responded to bevacizumab. The name of the study drug involved in this study is Ponatinib.

Key facts

Study ID

NCT02478164

Run by

Dana-Farber Cancer Institute

People needed

17

Starts

2015-07-13

Expected to finish

2018-05-09

Last updated by the study team

2018-07-24

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age ≥ 18 years
• Karnofsky performance status ≥ 60
• Participants must have histologically confirmed glioblastoma or variants. Subjects with initial diagnosis of a lower grade glioma are eligible if a subsequent biopsy is determined to be glioblastoma or variants.
• Patients must have an unequivocal progression by magnetic resonance imaging (MRI) or computed tomography (CT) scan. A scan must be performed within 14 days prior to registration and on a steroid dose that has been stable or decreasing for at least 5 days. If the steroid dose is increased between the date of imaging and initiation of study treatment, a new baseline MRI/CT is required.
• Participants must have bi-dimensionally measurable disease with a minimum measurement of 1 cm per dimension on MRI performed within 14 days prior to first treatment. If receiving corticosteroids, participants must be on a stable or decreasing dose of corticosteroids for at least 5 days prior to baseline MRI.
• There is no limit on the number of prior relapses but the most recent relapse must be the first relapse on a bevacizumab-containing regimen.
• Participants must have normal organ and marrow function as defined below:
• Leukocytes ≥3,000/mcL (≥ 3,000/mm3)
• Absolute neutrophil count ≥ 1,500/mcL (> 1,500/mm3)
• Platelets ≥ 100,000/mcL (≥ 100,000/ mm3)
• Total bilirubin ≤ 1.5 X institutional upper limit of normal, unless due to Gilbert's syndrome.
• AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional upper limit of normal
• Serum Creatinine ≤ 1.5 X institutional upper limit of normal or or creatinine clearance > 60 mL/min/1.73 m2 (per 24 hour urine collection or calculated according to the Cockcroft-Gault formula) for subjects with creatinine levels above the institutional normal
• Serum lipase and amylase ≤ 1.5 X institutional upper limit of normal.
• Participants must have fully recovered (grade ≤ 1 or baseline or deemed irreversible) from any clinically significant acute toxicity related to prior therapy (with the exception of lymphopenia, which is common after therapy with temozolomide). Patients who discontinued bevacizumab previously due to a bevacizumab-related toxicity will not be allowed to participate.
• The following time periods must have elapsed prior to the planned start date of study treatment:
• ≥2 weeks or 6 half lives from any approved TKIs or investigational agent, whichever is longer
• ≥4 weeks from prior cytotoxic therapy, except ≥ 3 weeks from last dose of temozolomide and ≥6 weeks from nitrosoureas or mitomycin C
• ≥2 weeks from non-cytotoxic agents
• ≥ 3 weeks from bevacizumab
• Participants must have developed progressive disease after receiving prior radiation therapy and must have an interval of at least 12 weeks from the completion of any radiation therapy to study entry (unless progressive tumor growth is outside the radiation field or there is histopathological confirmation of recurrent tumor).
• Participants may not have received prior therapy with any other Src, PDGFR, or FGFR inhibitor. Prior treatment with an anti-VEGFR or anti-VEGF agent is also allowed but only one relapse following a bevacizumab-containing regimen is allowed.
• For females of childbearing potential, a negative serum pregnancy test must be documented prior to registration.
• -- NOTE: In addition to screening, serum pregnancy test must be performed on females of childbearing potential within 72 hours before the start of investigational product. When possible, these tests can be one-in-the-same (if screening pregnancy test was performed within 72 hours of first ponatinib dose, no need to repeat).
• The effects of ponatinib on the developing human fetus are unknown. For this reason and because ponatinib is known to be teratogenic in animal models, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and through 4 months after the end of treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

You may not qualify if…

• Participants may not be receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ponatinib.
• Participants who have received prior treatment with interstitial brachytherapy, stereotactic radiosurgery, or implanted chemotherapy sources, such as wafers of polifeprosan 20 with carmustine
• Participants with poorly controlled diabetes defined as a HgbA1c ≥ 7.0%
• Participants with grade ≥ 3 peripheral motor or sensory neuropathy.
• Participants receiving any medications or substances that are moderate and strong inhibitors or inducers of CYP3A4, including enzyme-inducing anti-epileptic drugs (EIAEDs) within 14 days before the first dose of ponatinib will be excluded. This category includes phenobarbital, phenytoin, fosphenytoin, primidone, carbamazepine, and oxcarbazepine. Lists including medications and substances known or with the potential to interact with CYP3A4 isoenzymes are provided in Appendix B.
• -- NOTE: Participants must avoid consumption of Seville orange (and juice), grapefruit or grapefruit juice, grapefruit hybrids, pummelos and exotic citrus fruits from 7 days prior to the first dose of study drug and during the entire study treatment period due to potential CYP3A4 interaction.
• Participants taking medications that are known to be associated with Torsades de Pointes or QT prolongation. Refer to Tables C-1 and C-2 of Appendix C for a list of prohibited drugs.
• Participants cannot take any herbal preparations/medications on study or within 7 days prior to first dose of study drug, including but not limited to: St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, ginseng.
• Participants who underwent major surgery (including craniotomy) or significant traumatic injury within 28 days prior to initiating therapy. Baseline MRIs for participants who underwent salvage surgery must be obtained at least 4 weeks after procedure and there must be measurable disease.
• Participants who underwent minor surgical procedure within 7 days prior to initiating therapy.
• History of a bleeding disorder.
• Patients with gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE Grade >/= 3 within 30 days prior to study entry.
• Patients whose MRI scan demonstrates intratumoral hemorrhage or peritumoral hemorrhage are not eligible for treatment if deemed significant by the treating physician. If there are questions, the treating physician should contact the study's Overall PI, Dr. Lee
• History of acute pancreatitis within 1 year of study treatment or a history of chronic pancreatitis.
• History of alcohol abuse.
• Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL)
• Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
• Any history of myocardial infarction
• Any history of clinically significant (as determined by the treating physician) atrial arrhythmia
• Any history of ventricular arrhythmia
• Any history of Cerebrovascular accident or transient ischemic attack (TIA)
• Any history of peripheral arterial occlusive disease requiring rvascularization
• Unstable angina within 6 months prior to enrollment
• Congestive heart failure within 6 months prior to enrollment

Where it is running

• Massachusetts General Hospital — Boston, Massachusetts, United States
• Dana Farber Cancer Institute — Boston, Massachusetts, United States

Full record on ClinicalTrials.gov

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