D842-related Mutant GISTPhase 2NCT01243346
Study of Crenolanib for the Treatment of Patients With Advanced GIST With the D842-related Mutations and Deletions in the PDGFRA Gene
A Phase 2 study testing Crenolanib besylate (CP-868,596-26), Dose: 140mg BID in people with D842-related Mutant GIST, run by Arog Pharmaceuticals, Inc. at 2 sites in United States.
Trial summary
This Phase II study is designed to evaluate the antitumor efficacy and pharmacokinetics of crenolanib (CP-868,596) in patients with D842-related mutant metastatic GIST. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- D842-related Mutant GIST
- What is being tested?
- Crenolanib besylate (CP-868,596-26), Dose: 140mg BID
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- Apr 2011to Jul 2014
- 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
- Life expectancy of greater than 12 weeks
- Patient able and willing to provide informed consent
- Normal liver function, defined as AST and ALT ≤2.5x ULN, and Total Bilirubin ≤ 2x ULN.
- Total creatinine ≤ 1.5x ULN
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- ECOG Performance Status 0 - 2 (Appendix II)
- Patients must have histologically or cytologically confirmed GIST with a D842-related mutation or deletion on the PDGFRA gene
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. See Section 10.1.2 for the evaluation of measurable disease.
- Patients must have recovered from any prior therapy and completed the minimum of, either 5 half-lives of prior therapy or 2 weeks must have elapsed since prior treatment
Who cannot join
- Patient unable to provide informed consent
- ECOG Performance status > 2
- Any concurrent anticancer therapy, immunotherapy, or hormonal therapy.
- Any other investigational agents taken within 2 weeks of start of study drug or if study drug will commence within 5 half-lives of prior therapy
- Patients with known or active Hepatitis B or C; liver cirrhosis.
- Patients with active fungal, viral, and bacterial infections
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- Positive serum pregnancy test
- Pregnant or lactating women
- Patients on concomitant medications that induce or inhibit CYP3A4 (Appendix III)
- Patients with severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol e.g. impairment of gastrointestinal (GI) function, or GI disease that may significantly alter the absorption of the study drugs
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111-2497
Knight Cancer Institute, Oregon Health and Science University
Portland, Oregon, 97239-3098
About this study
Official title: Phase II Study of Crenolanib (CP-868,596), a Selective and Potent Inhibitor of PDGFR, for the Treatment of Patients With Advanced Gastrointestinal Stromal Tumors With the D842-related Mutations and Deletions, Including the D842V Mutation, in the PDGFRA Gene
This Phase II study is designed to evaluate the antitumor efficacy and pharmacokinetics of crenolanib (CP-868,596) in patients with D842-related mutant metastatic GIST.
Read the detailed description
Crenolanib (CP-868,596) is an orally bioavailable, selective inhibitor of PDGFR receptor tyrosine kinase with IC50s of 0.4 ng/mL and 0.8 ng/mL for PDGFRα and PDGFRβ, respectively.
In preclinical models of cell lines with the D842V mutation in the PDGFRA gene, crenolanib (CP-868,596) blocked phosphorylation of PDGFRα at nanomolar concentrations, suggesting that it may provide a clinical benefit to patients with D842V mutant GIST.
In addition, crenolanib was also active in inhibiting phosphorylation of cell lines with two point mutations (double mutants) PDGFRA V561D + D842V and PDGFRA T674I + D842V.
- Conditions
- D842-related Mutant GIST
- Being tested
- Crenolanib besylate (CP-868,596-26), Dose: 140mg BID
- Keywords
- Gastrointestinal Stromal Tumor, PDGFR Inhibitor, Crenolanib (CP-868,596)
- Medical subject headings
- Gastrointestinal Stromal Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Crenolanib besylate (CP-868,596-26), Dose: 140mg BIDDrug
Highly potent inhibitor of both PDGFR receptors alpha and beta
| Study group | Role | What they receive |
|---|---|---|
| Crenolanib (CP-868,596) | Experimental | Not described Receives: Drug: Crenolanib besylate (CP-868,596-26), Dose: 140mg BID |
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
To determine the response rate of patients with advanced D842V mutant GIST, when treated with Crenolanib (CP-868,596). Response will primarily be determined by RECIST criteria
Measured: 1.5 years
Secondary outcomes (3)
Progression free survival rate
To determine the progression free survival rate at 6 months in patients with advanced GIST with the D842V mutation in the PDGFRA gene, when treated with CP-868,596 (crenolanib).
Measured: 6 months
Obtain toxicity information
To obtain additional toxicity information in patients with advanced GIST with the D842V mutation in the PDGFRA gene.
Measured: 1 year
PKPD analysis
To obtain additional PK, pharmacodynamic and plasma inhibitory assay information in patients with advanced GIST with the D842V mutation in the PDGFRA gene.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Nov 2010 (estimated)
- Study startApr 2011
- Primary completionJul 2014
- Study completionJul 2014
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 D842-related Mutant GISTStudies 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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arog Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Margaret von Mehren, MD, Principal investigator, Fox Chase Cancer CenterMichael C Heinrich, MD, Principal investigator, OHSU Knight Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01243346
- Sponsor's protocol ID
- ARO-BRE-002
- Status last verified
- Jun 2018
- First submitted
- 17 Nov 2010
- Last updated
- 28 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Heinrich MC, Griffith D, McKinley A, Patterson J, Presnell A, Ramachandran A, Debiec-Rychter M. Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors. Clin Cancer Res. 2012 Aug 15;18(16):4375-84. doi: 10.1158/1078-0432.CCR-12-0625. Epub 2012 Jun 27.
PubMed 22745105
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Crenolanib (CP-868,596), a Selective and Potent Inhibitor of PDGFR, for the Treatment of Patients With Advanced Gastrointestinal Stromal Tumors With the D842-related Mutations and Deletions, Including the D842V Mutation, in the PDGFRA Gene
- ClinicalTrials.gov ID
- NCT01243346
- Acronym / sponsor ID
- ARO-BRE-002
- Conditions
- D842-related Mutant GIST
- Keywords
- Gastrointestinal Stromal Tumor, PDGFR Inhibitor, Crenolanib (CP-868,596)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Arog Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Apr 2011
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2014 (actual)
- First posted
- 18 Nov 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.
This Phase II study is designed to evaluate the antitumor efficacy and pharmacokinetics of crenolanib (CP-868,596) in patients with D842-related mutant metastatic GIST.
Detailed description
Crenolanib (CP-868,596) is an orally bioavailable, selective inhibitor of PDGFR receptor tyrosine kinase with IC50s of 0.4 ng/mL and 0.8 ng/mL for PDGFRα and PDGFRβ, respectively.
In preclinical models of cell lines with the D842V mutation in the PDGFRA gene, crenolanib (CP-868,596) blocked phosphorylation of PDGFRα at nanomolar concentrations, suggesting that it may provide a clinical benefit to patients with D842V mutant GIST.
In addition, crenolanib was also active in inhibiting phosphorylation of cell lines with two point mutations (double mutants) PDGFRA V561D + D842V and PDGFRA T674I + D842V.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Crenolanib (CP-868,596) | Experimental | Drug: Crenolanib besylate (CP-868,596-26), Dose: 140mg BID |
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
- Life expectancy of greater than 12 weeks
- Patient able and willing to provide informed consent
- Normal liver function, defined as AST and ALT ≤2.5x ULN, and Total Bilirubin ≤ 2x ULN.
Key exclusion criteria (10 listed)
- Patient unable to provide informed consent
- ECOG Performance status > 2
- Any concurrent anticancer therapy, immunotherapy, or hormonal therapy.
- Any other investigational agents taken within 2 weeks of start of study drug or if study drug will commence within 5 half-lives of prior therapy
- Patients with known or active Hepatitis B or C; liver cirrhosis.
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 besylate (CP-868,596-26), Dose: 140mg BIDHighly potent inhibitor of both PDGFR receptors alpha and beta | Drug | Crenolanib (CP-868,596) |
Primary outcome
The primary end-point is overall response rate
Time frame: 1.5 years
To determine the response rate of patients with advanced D842V mutant GIST, when treated with Crenolanib (CP-868,596). Response will primarily be determined by RECIST criteria
3 secondary outcomes
Progression free survival rate
Time frame: 6 months
Obtain toxicity information
Time frame: 1 year
PKPD analysis
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2018.
- Background: PubMed 22745105Heinrich MC, Griffith D, McKinley A, Patterson J, Presnell A, Ramachandran A, Debiec-Rychter M. Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors. Clin Cancer Res. 2012 Aug 15;18(16):4375-84. doi: 10.1158/1078-0432.CCR-12-0625. Epub 2012 Jun 27.
- Fox Chase Cancer CenterLink provided by the sponsor.
- AROG Pharmaceuticals, LLC, is dedicated to the scientific development of novel anticancer drugs for niche indicationsLink provided by the sponsor.
- OHSU Knight Cancer InstituteLink provided by the sponsor.
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.
Margaret von Mehren, MD principal investigator
Fox Chase Cancer Center
Michael C Heinrich, MD principal investigator
OHSU Knight 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 Crenolanib besylate (CP-868,596-26), Dose: 140mg BID in people with D842-related Mutant GIST, run by Arog Pharmaceuticals, Inc. 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 10 inclusion and 10 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 28 Jun 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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: 1.5 years). 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 NCT01243346, 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 28 Jun 2018.