Clinical Trials /

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

NCT02626364

Description:

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.

Related Conditions:
  • Glioblastoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Crenolanib in Recurrent/Refractory Glioblastoma With PDGFRA Gene Amplification
  • Official Title: Phase II Study of Single-agent Crenolanib in Recurrent/Refractory Glioblastoma With PDGFRA Gene Amplification

Clinical Trial IDs

  • ORG STUDY ID: ARO-015
  • NCT ID: NCT02626364

Conditions

  • Recurrent/Refractory Glioblastoma

Interventions

DrugSynonymsArms
crenolanibCP-868,596-26Treatment

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimentalcrenolanib 100mg PO TID
  • crenolanib

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival at 6 months
Time Frame:6 months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall response rate by RANO criteria
Time Frame:1 year
Safety Issue:
Description:
Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Time Frame:2 years
Safety Issue:
Description:
Measure:Change in symptom burden using The MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT)
Time Frame:2 years
Safety Issue:
Description:
Measure:Overall survival
Time Frame:3 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Arog Pharmaceuticals, Inc.

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