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Study of Crenolanib in Recurrent/Refractory Glioblastoma With PDGFRA Gene Amplification

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02626364
Recruitment Status : Completed
First Posted : December 10, 2015
Last Update Posted : July 20, 2020
Sponsor:
Information provided by (Responsible Party):
Arog Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE November 3, 2015
First Posted Date  ICMJE December 10, 2015
Last Update Posted Date July 20, 2020
Study Start Date  ICMJE April 2016
Actual Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 8, 2015)
Progression-free survival at 6 months [ Time Frame: 6 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 8, 2015)
  • Overall response rate by RANO criteria [ Time Frame: 1 year ]
  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: 2 years ]
  • Change in symptom burden using The MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) [ Time Frame: 2 years ]
  • Overall survival [ Time Frame: 3 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 27, 2016)
Duration of response [ Time Frame: 2 years ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Crenolanib in Recurrent/Refractory Glioblastoma With PDGFRA Gene Amplification
Official Title  ICMJE Phase II Study of Single-agent Crenolanib in Recurrent/Refractory Glioblastoma With PDGFRA Gene Amplification
Brief Summary This is a proof of concept, single-arm study to investigate crenolanib monotherapy in patients with recurrent/refractory glioblastoma with PDGFRA gene amplification by assessing the progression-free survival (PFS) at 6 months. Crenolanib will be given orally starting at 100 mg TID continuously until disease progression, unacceptable toxicity, or consent withdrawal.
Detailed Description

This is a proof of concept, single-arm study to investigate crenolanib monotherapy in patients with recurrent/refractory glioblastoma with PDGFRA gene amplification. Eligible patients include those with recurrent/refractory glioblastoma after prior therapy including surgery, radiation, and temozolomide. The trial is designed to assess the anti-tumor activity of crenolanib in recurrent/refractory glioblastoma with PDGFRA gene amplification based on the estimation of progression-free survival (PFS) at 6 months. Symptom burden will be evaluated using the M.D. Anderson Symptom Inventory-Brain Tumor (MDASI-BT).

Crenolanib will be administered orally continuously at 100 mg TID on a 28-day cycle basis . Patients are allowed to receive crenolanib for a maximum of 26 cycles if clinical benefit has been observed.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Recurrent/Refractory Glioblastoma
Intervention  ICMJE Drug: crenolanib
single-agent crenolanib at 100 mg PO TID
Other Name: CP-868,596-26
Study Arms  ICMJE Experimental: Treatment
crenolanib 100mg PO TID
Intervention: Drug: crenolanib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 17, 2020)
11
Original Estimated Enrollment  ICMJE
 (submitted: December 8, 2015)
34
Actual Study Completion Date  ICMJE July 2020
Actual Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients (male or female) ≥ 18 years of age.
  2. Histopathologically confirmed glioblastoma or gliosarcoma (WHO Grade IV) confirmed by local pathology tissue screening.
  3. Radiologic evidence of first recurrence after initial treatment (including surgery, radiation, and temozolomide) or tumor refractory to initial treatment without subsequent treatment in glioblastoma or gliosarcoma (WHO Grade IV). Transformation from a lower grade glioma previously treated with radiation and/or temozolomide to glioblastoma will be considered first recurrence for the purpose of this trial
  4. Tumor tissue available from original diagnosis and/or recurrence; a minimum of 1 FFPE archival tumor tissue block (preferred) or a minimum of 20 FFPE unstained slides from initial and/or most recent pre-registration biopsy or resection. It is recommended that at least 1 cm^2 of tissue composed primarily (defined as greater than 85%) of tumor is present.
  5. Confirmed PDGFRA amplification in the tumor tissue at the time of diagnosis or time of recurrence. Central confirmation of PDGFRA amplification will be performed by FISH in CLIA certified lab (ProPath). Signal quantitation will be used to generate a PDGFRA/centromere 4 ratio. PDGFRA to Centromere 4 ratios will be interpreted as follows: 1.8 to 2.2, borderline for amplification; 2.2 to 5.0, low-level amplification; and greater than 5.0 or clustered signals that are too numerous to count would be considered highly amplified. Tumor samples with PDGFRA to Centromere 4 ratios of 2.2 or higher will be considered amplified and therefore eligible for this trial. For patients with local CLIA testing demonstrating PDGFRA amplification by Next Generation Sequencing (Foundation Medicine, CMS400), central testing will not be required.
  6. Patients must have adequate organ function at baseline as defined below:

    • Adequate liver function (within 7 days of crenolanib commencement), as determined by:

    • Serum ALT, AST ≤ 2 × ULN
    • Normal serum total bilirubin (lower and upper limits of local Laboratory)
    • Adequate renal function assessed by: serum creatinine ≤ 1.5 × ULN
  7. KPS ≥ 60
  8. Recovered (returned to ≤ grade 1 as per CTCAE v4.03) from prior treatment-related toxicity.
  9. A minimum of 3 weeks must have elapsed from last intake of prior standard chemotherapy treatment.
  10. A minimum of 6 weeks must have elapsed from the last dose of nitrosoureas.
  11. A minimum of 5 half-lives of last dose of investigational agent must have elapsed prior to C1D1.
  12. More than 12 weeks from completion of chemoradiation, unless RANO criteria for early progression within 12 weeks of chemoradiation are met (See 18.1)
  13. Non-pregnant and non-nursing women of childbearing potential must have a negative serum or urine pregnancy test within 3 days of crenolanib commencement ("Women of childbearing potential" is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months).
  14. Women of childbearing potential and men must agree to use adequate contraception (simultaneous use of 2 methods of birth control) prior to study entry, for the duration of study participation and for 90 days following completion of therapy.
  15. Patient able and willing to provide informed consent.
  16. Ability to understand and willingness for follow-up visits.

Exclusion Criteria:

  1. Pre-existing liver diseases (i.e., cirrhosis, chronic hepatitis B or C, nonalcoholic steatohepatitis, and sclerosing cholangitis, etc.)
  2. Known positive for HIV
  3. Patients previously treated with bevacizumab.
  4. NYHA Class III-IV heart failure, myocardial infarction <6 months prior to study entry, and/or serious arrhythmia requiring anti-arrhythmic therapy
  5. Patients receiving concurrent anti-cancer treatment (chemotherapy, investigational agents, immunotherapy, endocrine therapy, or Optune®…)
  6. Patients with any other severe and/or uncontrolled concurrent disease affecting the cardiovascular system, liver, kidneys, hematopoietic system or else considered as clinically important by the investigator and that could be incompatible with patient's participation in this trial or would likely interfere with study procedures/results or compromise compliance with the protocol.
  7. Pregnant or breast-feeding women.
  8. Patients unable to swallow pills.
  9. Patients who are allergic to MRI contrast medium or unable to undergo MRI for any other reason.
  10. Patients unable to provide informed consent.
  11. Patients on EIADs are not eligible, unless the antiepileptic drug can be safely tapered and discontinued before C1D1.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02626364
Other Study ID Numbers  ICMJE ARO-015
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Arog Pharmaceuticals, Inc.
Study Sponsor  ICMJE Arog Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Barbara O'Brien, MD M.D. Anderson Cancer Center
PRS Account Arog Pharmaceuticals, Inc.
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP