Clinical Trials /

Study of Dasatinib in Combination With Everolimus for Children and Young Adults With Gliomas Harboring PDGFR Alterations

NCT03352427

Description:

This trial will evaluate the activity of dasatinib in combination with everolimus for children with gliomas harboring PDGFR alterations, including newly diagnosed high-grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG) after radiation (stratum A); and recurrent/progressive glioma (grade II-IV, including DIPG) (stratum B).

Related Conditions:
  • Diffuse Intrinsic Pontine Glioma
  • Glioma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Dasatinib in Combination With Everolimus for Children and Young Adults With Gliomas Harboring PDGFR/FGFR Alterations
  • Official Title: A Phase 2 Study of Dasatinib in Combination With Everolimus for Children With Gliomas Harboring PDGFR/FGFR Alterations

Clinical Trial IDs

  • ORG STUDY ID: UMCC 2017.042
  • SECONDARY ID: HUM00123094
  • NCT ID: NCT03352427

Conditions

  • Glioma

Interventions

DrugSynonymsArms
DasatinibDasatinib+Everolimus
EverolimusDasatinib+Everolimus

Purpose

This trial will evaluate the activity of dasatinib in combination with everolimus for children with gliomas harboring PDGFR or FGFR alterations.

Trial Arms

NameTypeDescriptionInterventions
Dasatinib+EverolimusExperimentalDasatinib = 60 mg/m2 orally twice daily Everolimus = starting dose of 3.0 mg/m2, with titration of dosing after first cycle to keep everolimus trough level of 5-15 ug/ml Both agents will be taken daily for 28 day cycles. Cycles will be repeated every 28 days and patients may receive up to 24 cycles.
  • Dasatinib
  • Everolimus

Eligibility Criteria

        Inclusion Criteria:

          -  Histological confirmation of a newly diagnosed high-grade glioma or DIPG (Stratum A)

          -  Histological confirmation (at diagnosis or relapse) of a recurrent or progressive
             grade II-IV glioma (including DIPG) (Stratum B)

          -  Participants must have a genomic (DNA and/or RNA) alteration (mutation, fusion, and/or
             amplification) involving PDGF-A, PDGF-B, PDGFR-A, PDGFR-B, FGF1, FGF3, FGFR1 or FGFR3,
             as identified by tumor sequencing.

          -  Age at enrollment: Greater than 1 year and less than 30 years

          -  BSA (body surface area): BSA greater than 0.3 m2

          -  Karnofsky (Measure of performance for cancer patients where 100% represents perfect
             health) > 50% for patients > 16 years of age and Lansky (Measure of performance for
             pediatric cancer patients where 100% represents perfect health) > 50% for patients <
             16 years of age. Neurologic deficits in patients with CNS tumors must have been
             relatively stable for a minimum of 7 days. Patients who are unable to walk because of
             paralysis, but who are able to sit in a wheelchair, will be considered ambulatory for
             the purpose of assessing the performance score.

          -  Adequate bone marrow function

          -  Adequate liver function

          -  Adequate renal and metabolic function

          -  Patients with known seizure disorder must have seizures adequately controlled with
             non- enzyme inducing antiepileptic medications

          -  No increase in steroid dose within the past 7 days

          -  Primary brain or spine tumor are eligible, including tumors with metastases, multiple
             lesions.

          -  Patients must have fully recovered from the acute toxic effects of all prior
             chemotherapy, immunotherapy, or radiotherapy.

          -  Myelosuppressive chemotherapy: Must not have received within 3 weeks.

          -  Hematopoietic growth factors: At least 7 days since the completion of therapy with a
             growth factor, 14 days for long- acting.

          -  Biologic (anti-neoplastic agent): At least 7 days or 3 half-lives (whichever is
             longer) since the completion of therapy.

          -  ≥ 12 weeks must have elapsed from craniospinal radiation; ≥ 2 weeks must have elapsed
             from focal radiation.

          -  > 3 weeks from major surgery. If recent craniotomy, adequate wound healing must be
             determined by neurosurgical team.

          -  Autologous Stem Cell Transplant or Rescue: No evidence of active graft vs. host
             disease and ≥ 4 weeks must have elapsed.

          -  All patients and/or a legal guardian must sign institutionally approved written
             informed consent and assent documents.

        Exclusion Criteria:

          -  Patients who are breastfeeding, pregnant or refuse to use an effective form of birth
             control are excluded.

          -  Patients with uncontrolled infection are excluded.

          -  Patients with known bleeding disorders or more than punctate intratumoral hemorrhage
             are excluded.

          -  Patients receiving other anti-neoplastic agents are excluded.

          -  Patients on enzyme-inducing anticonvulsive agents are excluded

          -  Patients requiring strong CYP3A4 or PGP inducers or inhibitors are excluded
             (verapamil, diltiazem, aprepitant, voriconazole, posaconazole, fluconazole (higher
             dose), phenytoin, carbamazepine, phenobarbital, (levetiracetam is ok), rifampin,
             rifabutin).

          -  Patients requiring anticoagulation or with uncontrolled bleeding are excluded.

          -  Patients on steroids for symptom management must be on a stable dose for 7 days prior
             to start of treatment.

          -  Patients within 1 year of allogeneic stem cell transplant, patients with active GVHD
             or requiring immunosuppression are excluded.

          -  Previous hypersensitivity to rapamycin or rapamycin derivatives
      
Maximum Eligible Age:30 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of patients alive without progression at 1 year
Time Frame:1 Year
Safety Issue:
Description:The primary endpoint is Progression Free Survival Rate (PFS). Progression will be defined as 25% increase in the size of the tumor or appearance of new lesions.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Michigan Cancer Center

Last Updated

November 29, 2017