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

This study is currently recruiting participants.
Verified June 2017 by Arog Pharmaceuticals, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02626364
First Posted: December 10, 2015
Last Update Posted: June 15, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Arog Pharmaceuticals, Inc.
  Purpose
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.

Condition Intervention Phase
Recurrent/Refractory Glioblastoma Drug: crenolanib Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Single-agent Crenolanib in Recurrent/Refractory Glioblastoma With PDGFRA Gene Amplification

Resource links provided by NLM:


Further study details as provided by Arog Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Progression-free survival at 6 months [ Time Frame: 6 months ]

Secondary Outcome Measures:
  • 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 ]

Other Outcome Measures:
  • Duration of response [ Time Frame: 2 years ]

Estimated Enrollment: 33
Study Start Date: April 2016
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: April 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
crenolanib 100mg PO TID
Drug: crenolanib
single-agent crenolanib at 100 mg PO TID
Other Name: CP-868,596-26

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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02626364


Contacts
Contact: Alima Tchafa, Ph.D. 214-593-0556 atchafa@arogpharma.com

Locations
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 75243
Contact: Marta Penas-Prado, M.D.         
Sponsors and Collaborators
Arog Pharmaceuticals, Inc.
Investigators
Principal Investigator: Marta Penas-Prado, MD M.D. Anderson Cancer Center
  More Information

Responsible Party: Arog Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02626364     History of Changes
Other Study ID Numbers: ARO-015
First Submitted: November 3, 2015
First Posted: December 10, 2015
Last Update Posted: June 15, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Crenolanib
Antineoplastic Agents