GliomaPhase 2NCT01229644
Study of Crenolanib, a Selective and Potent Inhibitor of PDGFR, for the Treatment of Adult Gliomas
A Phase 2 study testing Crenolanib (CP-868,596) in people with Glioma, run by Arog Pharmaceuticals, Inc. at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the antitumor efficacy of crenolanib (CP-868,596) in patients with recurrent high grade glioma and in patients with low grade glioma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioma
- What is being tested?
- Crenolanib (CP-868,596)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2011to Dec 2012
- Phase
- Phase 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
- Male or female, of any racial or ethnic group
- Age 18 years or older
- Patient able and willing to provide informed consent
- Adequate kidney and liver function
- Karnofsky Performance Status ≥ 70%
- Negative serum pregnancy test or child bearing potential terminated by surgery, radiation, menopause or current use of two approved methods of birth control
Show all 10Show fewer
- Imaging suggestive of malignant glioma (Cohort A)
- History of glioma with measurable disease by MRI (Cohorts B and C)
- Histologically confirmed GBM with radiographic progression (Cohort B). These patients are permitted to have had prior therapy including surgery, radiation, Temozolomide, irinotecan and bevacizumab.
- Histological confirmation of a low-grade glioma (Cohort C)
Who cannot join
- Patient unable to provide informed consent (comatose or markedly cognitively impaired)
- Female participants that are pregnant or breastfeeding
- Any other concurrent anticancer therapy
- Karnofsky Performance status < 70%
- Any other concurrent investigational agents within 4 weeks of start of study drug
- Patients with liver disease (known or active Hepatitis B or C; steatohepatitis; cirrhosis)
Show all 12Show fewer
- Hepatic:
- Bilirubin greater than 1x the upper limit of normal
- Transaminases greater than 1x the upper limit of normal
- Abnormal renal function
- o Serum creatinine >1.7 ng/dl
- Patients on concomitant medications that induce or inhibit CYP450, such as enzyme inducing anti-epileptic drugs (EIAEDs) (Appendix III) and troglitazone
Trial locations and contacts
1 site in 1 country.
United States1 site
Harold Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center
Dallas, Texas, 75390
About this study
Official title: A Phase II Study of Crenolanib (CP-868,596), a Selective and Potent Inhibitor of PDGFR, for the Treatment of Adult Gliomas
The purpose of this study is to evaluate the antitumor efficacy of crenolanib (CP-868,596) in patients with recurrent high grade glioma and in patients with low grade glioma.
Read the detailed description
This Phase II study is designed to evaluate the antitumor efficacy of crenolanib (CP-868,596) in patients with recurrent high grade glioma and in patients with low grade glioma. Concurrently, the pharmacokinetics, tumor penetration and ability of crenolanib (CP-868,596) to inhibit PDGFR signaling will be evaluated when given as neo-adjuvant therapy to patients with radiographic evidence of malignant glioma prior to initial surgery.
The study will enroll 3 different cohorts of patients in parallel. Cohort A will enroll patients scheduled to undergo craniotomy and resection of newly diagnosed gliomas (both low and high grade). Patients in cohort A will be treated with crenolanib (CP-868,596) (300mg once daily, on an empty stomach) in the neo-adjuvant setting for a minimum of 3 days prior to surgical resection of their tumor mass. Twelve patients will be accrued on this neo-adjuvant cohort that will allow us to assess the ability of crenolanib (CP-868,596) to penetrate the tumor, not only in grade 3 and 4 gliomas (anaplastic astrocytomas and glioblastomas) that have a leaky BBB, but also in grade 2 gliomas (low grade gliomas) that tend to have a more intact blood-brain barrier (BBB).
Pharmacokinetic, pharmacodynamic and biological assessments will be conducted with tissue samples (plasma and brain tissue) obtained from these patients, when feasible.
Cohorts B and C will enroll patients with recurrent high grade gliomas or biopsy proven low grade glioma, respectively, who have residual measurable disease. Patients in cohorts B and C will be treated with crenolanib (CP-868,596) (300mg once daily on an empty stomach) continuously until they fulfill one of the criteria for study discontinuation. Magnetic resonance imaging (MRI) will be done to assess the tumor response as well as progression free survival (PFS). The primary endpoint for both cohorts B and C will be overall response rate according to the Response Evaluation Criteria In Solid Tumors (RECIST), as assessed by standard imaging modalities. In addition, 6-month Progression-free survival (cohort B) and 1-year PFS will also be assessed.
- Conditions
- Glioma
- Being tested
- Crenolanib (CP-868,596)
- Keywords
- Glioma, Brain Cancer, Recurrent glioma, Low grade glioma, PDGFR Inhibitor, Crenolanib (CP-868,596), Neo-adjuvant Therapy
- Medical subject headings
- Glioma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Crenolanib (CP-868,596)Drug
Also called Crenolanib Besylate
Highly potent inhibitor of both PDGFR receptors alpha and beta
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Experimental | Adult newly diagnosed glioma (both low and high grade) patients, who are able to to take Crenolanib (CP-868,596) for at least 3 days prior to surgical resection. Receives: Drug: Crenolanib (CP-868,596) |
| Cohort B | Experimental | Adult patients with recurrent high grade glioma, including patients treated with bevacizumab. Patients are treated with Crenolanib (CP-868,596) continuously until they fulfill one of the criteria for study discontinuation. Receives: Drug: Crenolanib (CP-868,596) |
| Cohort C | Experimental | Adult patients with biopsy proven low grade glioma who have residual measurable disease. Patients are treated with Crenolanib (CP-868,596) continuously until they fulfill one of the criteria for study discontinuation. Receives: Drug: Crenolanib (CP-868,596) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary end-point is overall response rate
Measured: Tumor response will be assessed by MRI scans every 2 months until disease progression
Secondary outcomes (1)
The secondary end-point for this study is PFS
Measured: 6-months and 12-months PFS will be measured
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2010 (estimated)
- Study startApr 2011
- Primary completionJun 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arog Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Elizabeth Maher, M.D., Ph.D., Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01229644
- Sponsor's protocol ID
- ARO-BRE-001
- Status last verified
- Jul 2018
- First submitted
- 26 Oct 2010
- Last updated
- 5 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Elizabeth A. Maher1, Clinton Stewart2, Kimmo Hatanpaa1, Jack Raisanen1, Tomoyuki Mashimo1, Xiao-Li Yang1, Chaitanya Muralidhara3, Christopher Madden1, Abhijit Ramachandran3, Bruce Mickey1, Robert Bachoo1, 1University of Texas Southwestern Medical Center, Dallas, TX, 2St. Jude's Children's Research Hospital, Memphis, TN, 3AROG Pharmaceuticals, LLC, Dallas, TX Neoadjuvant administration of the potent PDGFR inhibitor, crenolanib, to malignant gliomas at initial diagnosis: does it hit the target?
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Crenolanib (CP-868,596), a Selective and Potent Inhibitor of PDGFR, for the Treatment of Adult Gliomas
- ClinicalTrials.gov ID
- NCT01229644
- Acronym / sponsor ID
- ARO-BRE-001
- Conditions
- Glioma
- Keywords
- Glioma, Brain Cancer, Recurrent glioma, Low grade glioma, PDGFR Inhibitor, Crenolanib (CP-868,596), Neo-adjuvant Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Arog Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Apr 2011
- Primary completion
- Jun 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 28 Oct 2010 (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.
The purpose of this study is to evaluate the antitumor efficacy of crenolanib (CP-868,596) in patients with recurrent high grade glioma and in patients with low grade glioma.
Detailed description
This Phase II study is designed to evaluate the antitumor efficacy of crenolanib (CP-868,596) in patients with recurrent high grade glioma and in patients with low grade glioma. Concurrently, the pharmacokinetics, tumor penetration and ability of crenolanib (CP-868,596) to inhibit PDGFR signaling will be evaluated when given as neo-adjuvant therapy to patients with radiographic evidence of malignant glioma prior to initial surgery.
The study will enroll 3 different cohorts of patients in parallel. Cohort A will enroll patients scheduled to undergo craniotomy and resection of newly diagnosed gliomas (both low and high grade). Patients in cohort A will be treated with crenolanib (CP-868,596) (300mg once daily, on an empty stomach) in the neo-adjuvant setting for a minimum of 3 days prior to surgical resection of their tumor mass. Twelve patients will be accrued on this neo-adjuvant cohort that will allow us to assess the ability of crenolanib (CP-868,596) to penetrate the tumor, not only in grade 3 and 4 gliomas (anaplastic astrocytomas and glioblastomas) that have a leaky BBB, but also in grade 2 gliomas (low grade gliomas) that tend to have a more intact blood-brain barrier (BBB).
Pharmacokinetic, pharmacodynamic and biological assessments will be conducted with tissue samples (plasma and brain tissue) obtained from these patients, when feasible.
Cohorts B and C will enroll patients with recurrent high grade gliomas or biopsy proven low grade glioma, respectively, who have residual measurable disease. Patients in cohorts B and C will be treated with crenolanib (CP-868,596) (300mg once daily on an empty stomach) continuously until they fulfill one of the criteria for study discontinuation. Magnetic resonance imaging (MRI) will be done to assess the tumor response as well as progression free survival (PFS). The primary endpoint for both cohorts B and C will be overall response rate according to the Response Evaluation Criteria In Solid Tumors (RECIST), as assessed by standard imaging modalities. In addition, 6-month Progression-free survival (cohort B) and 1-year PFS will also be assessed.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort A | Experimental | Drug: Crenolanib (CP-868,596)Adult newly diagnosed glioma (both low and high grade) patients, who are able to to take Crenolanib (CP-868,596) for at least 3 days prior to surgical resection. |
| Cohort B | Experimental | Drug: Crenolanib (CP-868,596)Adult patients with recurrent high grade glioma, including patients treated with bevacizumab. Patients are treated with Crenolanib (CP-868,596) continuously until they fulfill one of the criteria for study discontinuation. |
| Cohort C | Experimental | Drug: Crenolanib (CP-868,596)Adult patients with biopsy proven low grade glioma who have residual measurable disease. Patients are treated with Crenolanib (CP-868,596) continuously until they fulfill one of the criteria for study discontinuation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Male or female, of any racial or ethnic group
- Age 18 years or older
- Patient able and willing to provide informed consent
- Adequate kidney and liver function
- Karnofsky Performance Status ≥ 70%
Key exclusion criteria (12 listed)
- Patient unable to provide informed consent (comatose or markedly cognitively impaired)
- Female participants that are pregnant or breastfeeding
- Any other concurrent anticancer therapy
- Karnofsky Performance status < 70%
- Any other concurrent investigational agents within 4 weeks of start of study drug
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 |
|---|---|---|
| Crenolanib (CP-868,596)Also: Crenolanib BesylateHighly potent inhibitor of both PDGFR receptors alpha and beta | Drug | Cohort A, Cohort B, Cohort C |
Primary outcome
The primary end-point is overall response rate
Time frame: Tumor response will be assessed by MRI scans every 2 months until disease progression
1 secondary outcome
The secondary end-point for this study is PFS
Time frame: 6-months and 12-months PFS will be measured
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2018.
- BackgroundElizabeth A. Maher1, Clinton Stewart2, Kimmo Hatanpaa1, Jack Raisanen1, Tomoyuki Mashimo1, Xiao-Li Yang1, Chaitanya Muralidhara3, Christopher Madden1, Abhijit Ramachandran3, Bruce Mickey1, Robert Bachoo1, 1University of Texas Southwestern Medical Center, Dallas, TX, 2St. Jude's Children's Research Hospital, Memphis, TN, 3AROG Pharmaceuticals, LLC, Dallas, TX Neoadjuvant administration of the potent PDGFR inhibitor, crenolanib, to malignant gliomas at initial diagnosis: does it hit the target?
- Harold C. Simmons Cancer Center at UT Southwestern is the only NCI-designated Cancer Center in North TexasLink provided by the sponsor.
- AROG Pharmaceuticals is dedicated to the scientific development of novel anticancer drugs for niche indicationsLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Glioma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
Low Grade Astrocytoma, Low Grade Glioma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
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.
Elizabeth Maher, M.D., Ph.D. principal investigator
University of Texas Southwestern 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 Crenolanib (CP-868,596) in people with Glioma, run by Arog Pharmaceuticals, Inc. 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 10 inclusion and 12 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: stopped early, as of the sponsor's last update on 5 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 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?
The study was stopped early. 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?
The primary end-point is overall response rate (time frame: Tumor response will be assessed by MRI scans every 2 months until disease progression). 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 NCT01229644, 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 Jul 2018.