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

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ClinicalTrials.gov Identifier: NCT03352427
Recruitment Status : Recruiting
First Posted : November 24, 2017
Last Update Posted : December 2, 2017
Sponsor:
Information provided by (Responsible Party):
University of Michigan Cancer Center

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

Condition or disease Intervention/treatment Phase
Glioma Drug: Dasatinib Drug: Everolimus Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Dasatinib in Combination With Everolimus for Children With Gliomas Harboring PDGFR/FGFR Alterations
Actual Study Start Date : November 17, 2017
Estimated Primary Completion Date : December 1, 2024
Estimated Study Completion Date : December 1, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.

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




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



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Ages Eligible for Study:   1 Year to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

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): NCT03352427


Contacts
Contact: Carl Koschmann, M.D. 734-936-9814 ckoschma@med.umich.edu

Locations
United States, Michigan
University of Michigan Cancer Center Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Carl Koschmann, M.D.    734-936-9814    ckoschma@umich.edu   
Principal Investigator: Carl Koschmann, M.D.         
Sponsors and Collaborators
University of Michigan Cancer Center
Investigators
Principal Investigator: Carl Koschmann, M.D. University of Michigan Cancer Center

Responsible Party: University of Michigan Cancer Center
ClinicalTrials.gov Identifier: NCT03352427     History of Changes
Other Study ID Numbers: UMCC 2017.042
HUM00123094 ( Other Identifier: University of Michigan )
First Posted: November 24, 2017    Key Record Dates
Last Update Posted: December 2, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Everolimus
Sirolimus
Dasatinib
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action