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Study of Crenolanib in Recurrent/Refractory Glioblastoma With PDGFRA Gene Amplification | Clinical Trials | Clareo Health

COMPLETEDPHASE2

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

Phase II Study of Single-agent Crenolanib in Recurrent/Refractory Glioblastoma With PDGFRA Gene Amplification

NCT02626364•Arog Pharmaceuticals, Inc.

View on ClinicalTrials.gov

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.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

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
+10 more criteria

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.

Locations (1)

MD Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

April 1, 2016

Primary Completion Date

July 1, 2020

Completion Date

July 1, 2020

Last Updated

July 20, 2020

Enrollment

ACTUAL participants

Conditions

Recurrent/Refractory Glioblastoma

Interventions

crenolanib

DRUG