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

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ClinicalTrials.gov Identifier: NCT03352427
Recruitment Status : Recruiting
First Posted : November 24, 2017
Last Update Posted : May 17, 2019
Sponsor:
Information provided by (Responsible Party):
University of Michigan Rogel Cancer Center

Tracking Information
First Submitted Date  ICMJE November 20, 2017
First Posted Date  ICMJE November 24, 2017
Last Update Posted Date May 17, 2019
Actual Study Start Date  ICMJE December 6, 2017
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 15, 2019)
  • Progression-free survival in participants with newly diagnosed diffuse intrinsic pontine glioma (DIPG) [ Time Frame: 8 months ]
    Percentage of participants without progression, defined as 25% increase in the size of the tumor or appearance of new lesions.
  • Progression-free survival in participants with newly diagnosed high-grade glioma (HGG) [ Time Frame: 12 months ]
    Percentage of participants without progression, defined as 25% increase in the size of the tumor or appearance of new lesions.
  • Overall response rate (OR) (partial response or better) in participants with refractory or recurrent glioma [ Time Frame: 56 Days ]
    The overall response assessment will take into account response in both target and non-target lesions, as well as the appearance of new lesions. Partial Response (PR) will be defined as ≥50% decrease in size of tumor in comparison to baseline measurements. Complete Response (CR) will be defined as The disappearance of all abnormal signal. This includes return to normal size of the brainstem for brainstem lesions.
Original Primary Outcome Measures  ICMJE
 (submitted: November 20, 2017)
  • Proportion of patients alive without progression at 1 year [ Time Frame: 1 Year ]
    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.
  • Proportion of patients alive without progression at 2 years [ Time Frame: 2 Years ]
    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.
  • The proportion of patients that respond to treatment [ Time Frame: 56 Days ]
    The overall response assessment will take into account response in both target and non-target lesions, as well as the appearance of new lesions. Partial Response (PR) will be defined as ≥50% decrease in size of tumor in comparison to baseline measurements. Complete Response (CR) will be defined as The disappearance of all abnormal signal. This includes return to normal size of the brainstem for brainstem lesions.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2019)
  • Overall Survival [ Time Frame: 1 year ]
  • Overall Survival [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Dasatinib in Combination With Everolimus for Children and Young Adults With Gliomas Harboring PDGFR Alterations
Official Title  ICMJE A Phase 2 Study of Dasatinib in Combination With Everolimus for Children With Gliomas Harboring PDGFR Alterations
Brief Summary 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).
Detailed Description Not Provided
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
  • Glioma
  • High Grade Glioma
  • Pontine Tumors
Intervention  ICMJE
  • Drug: Dasatinib
    60 mg/m2 orally twice daily
  • Drug: Everolimus
    3.0 mg/m2, with titration of dosing after first cycle to keep trough level of 5-15 ug/ml
Study Arms  ICMJE Experimental: Dasatinib+Everolimus

Dasatinib = 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.

Interventions:
  • Drug: Dasatinib
  • Drug: Everolimus
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 20, 2017)
32
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2024
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histological confirmation of a newly diagnosed high-grade glioma or diffuse intrinsic pontine glioma (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 or PDGFR-B, as identified by tumor sequencing.
  • Age at enrollment: Greater than 1 year and less than 50 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 per protocol
  • Adequate liver function per protocol
  • Adequate renal and metabolic function per protocol
  • 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.
  • Radiation therapy:

    • Stratum A: ≥ 2 weeks and </= to 12 weeks must have elapsed from radiation.
    • Stratum B: ≥ 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 receiving other anti-neoplastic agents are excluded.
  • Patients requiring strong CYP3A4 or PGP inhibitors are excluded (per protocol)
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 50 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Carl Koschmann, M.D. 734-936-9814 ckoschma@med.umich.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03352427
Other Study ID Numbers  ICMJE UMCC 2017.042
HUM00123094 ( Other Identifier: University of Michigan )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Michigan Rogel Cancer Center
Study Sponsor  ICMJE University of Michigan Rogel Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Carl Koschmann, M.D. University of Michigan Rogel Cancer Center
PRS Account University of Michigan Rogel Cancer Center
Verification Date May 2019

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