GliomaPhase 2NCT01140568
Study of Platelet Derived Growth Factor Receptor (PDGFR) in Recurrent Malignant Gliomas
A Phase 2 study testing nilotinib in people with Glioma, run by David Piccioni, M.D., Ph.D at 1 site in United States.
Trial summary
The purpose of this study is to determine the survival, disease response, and side effects of Tasigna® (nilotinib) in patients who have malignant gliomas and are positive for Platelet Derived Growth Factor Receptor (PDGFR) amplification. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioma
- What is being tested?
- nilotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Apr 2010to Jan 2019
- 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
- Ability to provide written informed consent prior to participation in the study and any related procedures being performed.
- Participants must have agreed to and signed an authorization for the release of their protected health information.
- Subjects must be able to adhere to the dosing and visit schedules, and agree to record medication times accurately and consistently in a daily diary.
- Participants must have a life expectancy of at least 8 weeks.
- Patients greater than 18 years of age.
- Histologically documented diagnosis of proven glioblastoma (GBM), or anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and anaplastic mixed oligoastrocytoma (AMO). Patients are eligible if the original local pathology was lower-grade glioma. Pathology will be read centrally to confirm diagnosis.
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- Documentation of amplified PDGFRA by fluorescent in-situ hybridization (FISH), colorimetric in-situ hybridization (CISH), or quantitative PCR from tumor tissue (=>3 copy number). Availability of unstained paraffin slides or the paraffin block of pretreatment baseline tissue is required for eligibility and for molecular analysis and would help to identify molecular predictors of outcome (all patients).
- Participants must have a Karnofsky Performance Status (KPS) ≥ 60.
- Adequate end organ function, defined as the following:
- Hematology:
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelet count ≥ 100 x 109/L
- Hemoglobin ≥ 9.0 g/dL
- White blood cell (WBC) count ≥ 3.0 x 109/L
- Biochemistry:
- AST/SGOT and ALT/SGPT ≤ 2.5 x institution's ULN
- Total bilirubin ≤ 1.5 x institution's ULN
- Serum creatinine ≤ 1.5 x institution's ULN or 24-hour creatinine clearance ≥ 50 ml/min
- Alkaline phosphatase (ALP) ≤ 2.5 x ULN unless considered tumor related
- Patients must have the following laboratory values within normal limits (WNL) at the local institution lab or corrected to WNL with supplements prior to first dose of study medication.
- Potassium (WNL)
- Magnesium (WNL)
- Phosphorous (WNL)
- Calcium (WNL)
- Coagulation studies:
- INR < 1.5
- PTT within institution's normal range, unless receiving therapeutic low molecular weight heparin
- Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
- Participants 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 for at least 5 days. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI/CT is required. The same type of scan, i.e., MRI or CT must be used throughout the period of protocol treatment for tumor measurement. A patient who develops a contraindication to undergo an MRI scan during study treatment may remain on study and undergo contrast enhanced CT scans.
- Patients must have failed prior radiation therapy and must have an interval of greater than or equal to 60 days from the completion of radiation therapy to study entry.
- Subjects must have recovered from the toxic effects of prior therapy. Residual toxicity from any previous treatment must be ≤ Grade 1.
- Patients must have sufficient time for recovery from prior therapy: 28 days from any investigational agent, 28 days from prior cytotoxic therapy (except 23 days from prior temozolomide, 14 days from vincristine, 42 days from nitrosoureas, 21 days from procarbazine administration), and 7 days for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count).
- Patients with prior therapy that included interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true progressive disease rather than radiation necrosis based upon positron emission tomography (PET), Thallium scanning, MR spectroscopy or surgical documentation of disease.
- Subjects who have undergone recent resection of recurrent or progressive tumor will be eligible as long as all of the following conditions apply:
- Prior to initiating therapy, 4 weeks must have elapsed since surgery;
- Subjects must have recovered from surgical-related trauma;
- Wound healing needs to have occurred.
Who cannot join
- Patients who received PDGFR inhibitors (imatinib, sunitinib, nilotinib, etc.) previously are excluded (patients who received PDGFR antibody based treatment however are allowed).
- History of intratumoral or peritumoral hemorrhage if deemed significant by the treating physician.
- For patients requiring anticoagulation therapy, only therapeutic low molecular weight heparin or factor Xa inhibitors are permitted.
- Due to the potential interaction between nilotinib and enzyme-inducing anti-epileptic drugs (EIAED), only patients on non-enzyme inducing anti-epileptic drugs (NEIAED) or on no anti-epileptic drugs are eligible.
- Patient is < 3 years free of another primary malignancy except: if the other primary malignancy is not currently clinically neither significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
- Female patients who are pregnant or breast-feeding, or intends to become pregnant during the study.
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- Any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy.
- Patient has a rare hereditary problem of galactose intolerance, severe lactase deficiency or of glucose-galactose malabsorption.
- Patients with any disease that will obscure toxicity or dangerously alter drug metabolism.
- Patient with electrolyte abnormality (e.g., hypokalemia, hypomagnesemia, hypophosphatemia, hyperkalemia, hypocalcemia, hyponatremia) unless the level can be corrected to normal levels prior to initiating study drug.
- Patient has a known diagnosis of human immunodeficiency virus (HIV) infection.
- Patient received chemotherapy within 4 weeks (6 weeks for nitrosourea) prior to study entry, unless the disease is rapidly progressing.
- Concomitant use of any anti-cancer therapy or radiation therapy, or any other investigational agent.
- Impaired cardiac function including any of the following:
- Congenital long QT syndrome or a known family history of long QT syndrome;
- History or presence of clinically significant ventricular or atrial tachyarrhythmias
- Clinically significant resting bradycardia (< 50 beats per minute)
- Inability to monitor the QT interval by ECG
- QTc > 450 msec on baseline ECG. If QTc > 450 and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc
- Myocardial infarction within 1 year of starting study drug
- Other clinically significant heart disease (e.g., unstable angina, congestive heart failure, or uncontrolled hypertension)
- Patients currently receiving treatment with strong CYP3A4 inhibitors and treatment cannot be either discontinued or switched to a different medication prior to starting study drug. See link for complete list of CYP3A4 inhibitors (http://medicine.iupui.edu/clinpharm/ddis/table.asp)
- Patient currently receiving treatment with any medications that have the potential to prolong the QT interval and cannot be either discontinued or switched to a different medication prior to starting study drug. See link for a comprehensive list of agents that prolong the QT interval (http://www.azcert.org/medical-pros/drug-lists/printable-drug-list.cfm).
- Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection or gastric bypass surgery).
- Acute or chronic pancreatic disease.
- Another malignancy that is clinically significant or requires active intervention (chemotherapy or radiation)
- Severe or uncontrolled medical conditions (i.e., uncontrolled diabetes, active or uncontrolled infection).
- Acute or chronic liver or severe renal disease
- History of significant congenital or acquired bleeding disorder.
- Major surgery within 4 weeks prior to Day 1 of study or who have not recovered from prior surgery.
- Treatment with other investigational agents within 30 days of Day 1.
- History of non-compliance to medical regimens or inability to grant consent.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Rebecca and John Moores UCSD Cancer Center
La Jolla, California, 92093
About this study
Official title: A Phase II Study of PDGFR Kinase Inhibitor in Biomarker-Enriched Recurrent Malignant Gliomas
The purpose of this study is to determine the survival, disease response, and side effects of Tasigna® (nilotinib) in patients who have malignant gliomas and are positive for Platelet Derived Growth Factor Receptor (PDGFR) amplification. This study is designed to test the hypothesis that patients with malignant gliomas with PDGFR amplification are sensitive to PDGFR kinase inhibitors.
Read the detailed description
Malignant gliomas (MG), including anaplastic gliomas (AG) and glioblastoma (GBM), are the most common primary brain tumor. Standard of care (surgery, radiotherapy, and temozolomide at initial diagnosis) results in a median survival of only 14 months. For patients with recurrent disease, conventional chemotherapy is generally ineffective with response rates <20%. Clearly there is need for improved treatments. Recent genome-wide studies have confirmed that GBM is a heterogeneous group of diseases that can be subclassified by shared genetic aberrations. The implication is that, in part, the underlying genetics may determine responsiveness to treatments and thus allow us to personalize therapy.
This is an, open-label, non-randomized, phase II study with oral nilotinib in adult patients with biomarker-enriched, recurrent malignant gliomas who have developed tumor progression after standard therapy. Patients will be treated with oral nilotinib (starting with the labeled dose of 400 mg) daily until disease progression or intolerance. One cycle is defined as 28 days.
Approximately 50 evaluable patients will be enrolled in this study, with 32 (grade IV) and 18 (grade III) in separate arms.
All patients will undergo clinical evaluation after each 28-day cycle. Neuroimaging studies (MRI) will be performed at baseline, 4 weeks, 8 weeks and then after every 2 cycles (8 weeks). If a contraindication for MRI's exists, patients will undergo contrast-enhanced CT scans. Laboratory tests will be obtained weekly during the first 4 weeks, and then on days 1 and 15 of all subsequent cycles. Patients will remain on study medication unless they develop tumor progression or unacceptable toxicity.
- Conditions
- Glioma
- Being tested
- nilotinib
- Keywords
- glioma, PDGFR, kinase, inhibitor, malignant, nilotinib
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nilotinibDrug
Also called Tasigna
400mg po (orally) BID (twice daily)
| Study group | Role | What they receive |
|---|---|---|
| nilotinib | Experimental | Patients will take nilotinib twice daily at the standard dose of 400mg taken by mouth twice a day until disease progression or development of unacceptable side effects. Receives: Drug: nilotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Who Had 6-month Progression-free Survival.
Progression was defined by McDonald Criteria: A 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR clear clinical worsening OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
Measured: 6 months
Secondary outcomes (1)
Overall Response Rate
How many patients who had decrease in tumor size or complete disappearance of tumor.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2010 (estimated)
- Study start21 Apr 2010
- Primary completion5 Oct 2016
- Study completionJan 2019
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for GliomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- David Piccioni, M.D., Ph.D
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor-investigator, David Piccioni, M.D., Ph.D, University of California, San Diego
- Investigators
- David Piccioni, MD, PhD, Principal investigator, University of California Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01140568
- Sponsor's protocol ID
- 091728
- Status last verified
- Apr 2020
- First submitted
- 8 Jun 2010
- Last updated
- 5 May 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Piccioni D, Juarez TM, Kesari SL, Rose L, Nomura N, Kesari S. Phase II trial of nilotinib in PDGFR-alpha-enriched recurrent high-grade gliomas. Neurooncol Adv. 2025 Jul 10;7(1):vdaf150. doi: 10.1093/noajnl/vdaf150. eCollection 2025 Jan-Dec.
PubMed 40709015
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of PDGFR Kinase Inhibitor in Biomarker-Enriched Recurrent Malignant Gliomas
- ClinicalTrials.gov ID
- NCT01140568
- Acronym / sponsor ID
- 091728
- Conditions
- Glioma
- Keywords
- glioma, PDGFR, kinase, inhibitor, malignant, nilotinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- David Piccioni, M.D., Ph.DUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- 21 Apr 2010 (actual)
- Primary completion
- 5 Oct 2016 (actual)
- Study completion
- Jan 2019 (actual)
- First posted
- 9 Jun 2010 (estimated)
- Results
- Posted 24 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the survival, disease response, and side effects of Tasigna® (nilotinib) in patients who have malignant gliomas and are positive for Platelet Derived Growth Factor Receptor (PDGFR) amplification. This study is designed to test the hypothesis that patients with malignant gliomas with PDGFR amplification are sensitive to PDGFR kinase inhibitors.
Detailed description
Malignant gliomas (MG), including anaplastic gliomas (AG) and glioblastoma (GBM), are the most common primary brain tumor. Standard of care (surgery, radiotherapy, and temozolomide at initial diagnosis) results in a median survival of only 14 months. For patients with recurrent disease, conventional chemotherapy is generally ineffective with response rates <20%. Clearly there is need for improved treatments. Recent genome-wide studies have confirmed that GBM is a heterogeneous group of diseases that can be subclassified by shared genetic aberrations. The implication is that, in part, the underlying genetics may determine responsiveness to treatments and thus allow us to personalize therapy.
This is an, open-label, non-randomized, phase II study with oral nilotinib in adult patients with biomarker-enriched, recurrent malignant gliomas who have developed tumor progression after standard therapy. Patients will be treated with oral nilotinib (starting with the labeled dose of 400 mg) daily until disease progression or intolerance. One cycle is defined as 28 days.
Approximately 50 evaluable patients will be enrolled in this study, with 32 (grade IV) and 18 (grade III) in separate arms.
All patients will undergo clinical evaluation after each 28-day cycle. Neuroimaging studies (MRI) will be performed at baseline, 4 weeks, 8 weeks and then after every 2 cycles (8 weeks). If a contraindication for MRI's exists, patients will undergo contrast-enhanced CT scans. Laboratory tests will be obtained weekly during the first 4 weeks, and then on days 1 and 15 of all subsequent cycles. Patients will remain on study medication unless they develop tumor progression or unacceptable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| nilotinib | Experimental | Drug: nilotinibPatients will take nilotinib twice daily at the standard dose of 400mg taken by mouth twice a day until disease progression or development of unacceptable side effects. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (37 listed)
- Ability to provide written informed consent prior to participation in the study and any related procedures being performed.
- Participants must have agreed to and signed an authorization for the release of their protected health information.
- Subjects must be able to adhere to the dosing and visit schedules, and agree to record medication times accurately and consistently in a daily diary.
- Participants must have a life expectancy of at least 8 weeks.
- Patients greater than 18 years of age.
Key exclusion criteria (32 listed)
- Patients who received PDGFR inhibitors (imatinib, sunitinib, nilotinib, etc.) previously are excluded (patients who received PDGFR antibody based treatment however are allowed).
- History of intratumoral or peritumoral hemorrhage if deemed significant by the treating physician.
- For patients requiring anticoagulation therapy, only therapeutic low molecular weight heparin or factor Xa inhibitors are permitted.
- Due to the potential interaction between nilotinib and enzyme-inducing anti-epileptic drugs (EIAED), only patients on non-enzyme inducing anti-epileptic drugs (NEIAED) or on no anti-epileptic drugs are eligible.
- Patient is < 3 years free of another primary malignancy except: if the other primary malignancy is not currently clinically neither significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
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 |
|---|---|---|
| nilotinibAlso: Tasigna400mg po (orally) BID (twice daily) | Drug | nilotinib |
Primary outcome
Number of Patients Who Had 6-month Progression-free Survival.
Time frame: 6 months
Progression was defined by McDonald Criteria: A 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR clear clinical worsening OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).
1 secondary outcome
Overall Response Rate
Time frame: 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40709015Piccioni D, Juarez TM, Kesari SL, Rose L, Nomura N, Kesari S. Phase II trial of nilotinib in PDGFR-alpha-enriched recurrent high-grade gliomas. Neurooncol Adv. 2025 Jul 10;7(1):vdaf150. doi: 10.1093/noajnl/vdaf150. eCollection 2025 Jan-Dec.
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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.
David Piccioni, MD, PhD principal investigator
University of California Medical Center
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 nilotinib in people with Glioma, run by David Piccioni, M.D., Ph.D 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 37 inclusion and 32 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 5 May 2020. 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 Apr 2020). 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?
Number of Patients Who Had 6-month Progression-free Survival. (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01140568, which also lists 1 linked publication.
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 5 May 2020.