GlioblastomaPhase 2NCT02478164
Trial of Ponatinib in Patients With Bevacizumab-Refractory Glioblastoma
A Phase 2 study testing Ponatinib in people with Glioblastoma, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Ponatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 2 sitesUnited States
- Study dates
- 13 Jul 2015to 9 May 2018
- 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
- 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.
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- 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.
- Ability to understand and the willingness to sign a written informed consent document.
- NOTE: Consent documents can be signed up to 30 days prior to registration. If >30 days has elapsed since patient signed the consent document, s/he must re-consent (new signature) before proceeding to register onto study.
- Participants must have sufficient tissue from prior surgery for confirmation of diagnosis and correlative studies. The following amount of tissue is required:
- 15 (5 μm thick) unstained formalin fixed paraffin embedded (FFPE) sections
- 1-2 H\&E stained slides, or additional unstained 5 μm slide(s) for staining
- Protocol treatment plan must include beginning therapy within 5 consecutive days after registration.
Who cannot join
- 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.
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- --- 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
- Venous thromboembolism including deep venous thrombosis or pulmonary embolism within 6 months prior to enrollment
- Unacceptable Screening Baseline Cardiovascular Assessment:
- Baseline MUGA or Echocardiogram demonstrating LVEF < 50 %
- QTc > 480 msec on screening ECG (using the QTcF formula)
- Uncontrolled hypertension (diastolic blood pressure >90 mm Hg; systolic >140 mm Hg). Patients with hypertension should be under treatment on study entry to effect blood pressure control.
- Ongoing or active infection. The requirement for intravenous (IV) antibiotics is considered active infection.
- Known history of human immunodeficiency virus (HIV). Testing is not required in the absence of prior documentation or known history.
- Pregnant or breastfeeding.
- -- Pregnant women are excluded from this study because ponatinib has potential for teratogenic or abortifacient effects in animal models. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with ponatinib, breastfeeding should be discontinued if the mother is treated with ponatinib. These potential risks may also apply to other agents used in this study.
- Malabsorption syndrome or other gastrointestinal illness that could affect oral absorption of study drugs.
- Individuals with a history of a different malignancy, other than cervical cancer in situ, basal cell or squamous cell carcinoma of the skin, are ineligible, except if they have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy OR if the other primary malignancy is neither currently clinically significant nor requiring active intervention.
- Any condition or illness that, in the opinion of the Investigator, would compromise patient safety or interfere with the evaluation of the drug.
- HIV-positive individuals on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ponatinib. In addition, these individuals are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
Official title: Phase II Trial of Ponatinib in Patients With Bevacizumab-Refractory Glioblastoma
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.
Read the detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved Ponatinib for your specific disease but it has been approved for other uses.
Ponatinib is a drug that may stop cancer cells from growing by affecting different kinds of proteins in cancer cells. Glioblastoma cells can be driven by mutated forms of a protein called c-kit (KIT) which are present in glioblastoma cells. Laboratory studies suggest that ponatinib has activity against mutated forms of (KIT) which is important in glioblastoma and therefore suggests that ponatinib may help to control the growth of glioblastoma. In this research study the study team is looking to see if ponatinib is safe and is able to control the growth of glioblastoma in people who have not responded to treatment with bevacizumab.
- Conditions
- Glioblastoma
- Being tested
- Ponatinib
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PonatinibDrug
Also called ponatinib hydrochloride, Iclusig
| Study group | Role | What they receive |
|---|---|---|
| Ponatinib | Experimental | Drug will be administered once daily per cycle through oral ingestion. Receives: Drug: Ponatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 months
Secondary outcomes (3)
Best Radiographic Response
Radiographic response was established based on Response Assessment in Neuro-Oncology (RANO) criteria with 5 potential categories: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive disease (PD) and Unknown status.
Measured: Disease was assessed radiographically for response every 8 weeks, assessed up to 24 weeks.
Overall Survival (OS)
OS based on Kaplan-Meier is defined as the time from study entry to death or date last known alive.
Measured: 2 years
Progression-Free Survival (PFS)
PFS based on Kaplan-Meier is defined as the time from study entry to the earliest documentation of disease progression or death. Progressive disease was established based on Response Assessment in Neuro-Oncology (RANO) criteria.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2015 (estimated)
- Study start13 Jul 2015
- Primary completion8 Jul 2017
- Study completion9 May 2018
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 GlioblastomaStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Eudocia Quant Lee, MD, Dana-Farber Cancer Institute
- Investigators
- Eudocia Lee, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02478164
- Sponsor's protocol ID
- 15-163
- Status last verified
- Jun 2018
- First submitted
- 12 Jun 2015
- Last updated
- 24 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Ponatinib in Patients With Bevacizumab-Refractory Glioblastoma
- ClinicalTrials.gov ID
- NCT02478164
- Acronym / sponsor ID
- 15-163
- Conditions
- Glioblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Study start
- 13 Jul 2015 (actual)
- Primary completion
- 8 Jul 2017 (actual)
- Study completion
- 9 May 2018 (actual)
- First posted
- 23 Jun 2015 (estimated)
- Results
- Posted 2 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved Ponatinib for your specific disease but it has been approved for other uses.
Ponatinib is a drug that may stop cancer cells from growing by affecting different kinds of proteins in cancer cells. Glioblastoma cells can be driven by mutated forms of a protein called c-kit (KIT) which are present in glioblastoma cells. Laboratory studies suggest that ponatinib has activity against mutated forms of (KIT) which is important in glioblastoma and therefore suggests that ponatinib may help to control the growth of glioblastoma. In this research study the study team is looking to see if ponatinib is safe and is able to control the growth of glioblastoma in people who have not responded to treatment with bevacizumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ponatinib | Experimental | Drug: PonatinibDrug will be administered once daily per cycle through oral ingestion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- 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.
Key exclusion criteria (38 listed)
- 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.
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 |
|---|---|---|
| PonatinibAlso: ponatinib hydrochloride, Iclusig | Drug | Ponatinib |
Primary outcome
3-Month Progression-Free Survival (PFS3)
Time frame: 3 months
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 secondary outcomes
Best Radiographic Response
Time frame: Disease was assessed radiographically for response every 8 weeks, assessed up to 24 weeks.
Overall Survival (OS)
Time frame: 2 years
Progression-Free Survival (PFS)
Time frame: 3 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Eudocia Lee, MD principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ponatinib in people with Glioblastoma, run by Dana-Farber Cancer Institute at 2 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 31 inclusion and 38 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 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 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 2 Apr 2018). 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?
3-Month Progression-Free Survival (PFS3) (time frame: 3 months). 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 2018.