Trial of Ponatinib in Patients With Bevacizumab-Refractory Glioblastoma

NCT02478164 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 15-163
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Glioblastoma

Outcome Measures

Primary Outcomes (1)

• 3-Month Progression-Free Survival (PFS3)

  PFS3 is the proportion of patients remaining alive and progression-free at 3-months from study entry. Progressive disease was established based on Response Assessment in Neuro-Oncology (RANO) criteria. RANO criteria has 5 potential categories: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive disease (PD) and Unknown. CR: disappearance of all enhancing lesions, stable or improved non-enhancing lesions, and stable or improved clinically. PR: \>= 50% decrease in sum of perpendicular diameters of all measurable enhancing lesions, no progression of non-measurable disease, stable or improved non-enhancing lesions, and stable or improved clinically. PD: \>25% increase in sum of perpendicular diameters of all measurable enhancing lesions, significant increase of non-enhancing lesions, any new lesions, clear clinical deterioration, failure to return for evaluation due to death or deteriorating condition. SD: does not qualify for CR,PR or PD.

  3 months

Secondary Outcomes (3)

• Best Radiographic Response

  Disease was assessed radiographically for response every 8 weeks, assessed up to 24 weeks.

• Overall Survival (OS)

  2 years

• Progression-Free Survival (PFS)

  3 months

Study Arms (1)

Ponatinib

EXPERIMENTAL

Drug will be administered once daily per cycle through oral ingestion.

Drug: Ponatinib

Interventions

Ponatinib DRUG

Also known as: ponatinib hydrochloride, Iclusig

Ponatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

ponatinib

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: Eudocia Q. Lee, MD, MPH
• Organization: Dana-Farber Cancer Institute

eqlee@partners.org

617-632-2166

Study Officials

• Eudocia Lee, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Eudocia Lee, MD

Study Record Dates

• First Submitted: June 12, 2015
• First Posted: June 23, 2015
• Study Start: July 13, 2015
• Primary Completion: July 8, 2017
• Study Completion: May 9, 2018
• Last Updated: July 24, 2018
• Results First Posted: April 2, 2018

Record last verified: 2018-06

Locations

US (2)