Study of Dasatinib in Combination With Everolimus for Children and Young Adults With Gliomas Harboring Platelet-Derived Growth Factor Receptor (PDGFR) Alterations

Glioma Clinical Trial

Official title:

A Phase 2 Study of Dasatinib in Combination With Everolimus for Children With Gliomas Harboring PDGFR Alterations

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03352427
• Other study ID #: UMCC 2017.042
• Secondary ID: HUM00123094
• Status: Terminated
• Phase: Phase 2
• Start date: December 6, 2017
• Est. completion date: May 15, 2019

Study information

• Verified date: September 2022
• Source: University of Michigan Rogel Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: May 15, 2019
• Est. primary completion date: April 17, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Stem Neoplasms
• Glioma
• High Grade Glioma
• Pontine Tumors

Intervention

Drug:
• Dasatinib
60 mg/m2 orally twice daily
• Everolimus
3.0 mg/m2, with titration of dosing after first cycle to keep trough level of 5-15 ug/ml

Locations

Country	Name	City	State
United States	University of Michigan Cancer Center	Ann Arbor	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
University of Michigan Rogel Cancer Center

Country where clinical trial is conducted

United States, 

References & Publications (1)

Miklja Z, Yadav VN, Cartaxo RT, Siada R, Thomas CC, Cummings JR, Mullan B, Stallard S, Paul A, Bruzek AK, Wierzbicki K, Yang T, Garcia T, Wolfe I, Leonard M, Robertson PL, Garton HJ, Wahl DR, Parmar H, Sarkaria JN, Kline C, Mueller S, Nicolaides T, Glasse — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival in Participants With Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG)	Percentage of participants without progression, defined as 25% increase in the size of the tumor or appearance of new lesions.	8 months
Primary	Progression-free Survival in Participants With Newly Diagnosed High-grade Glioma (HGG)	Percentage of participants without progression, defined as 25% increase in the size of the tumor or appearance of new lesions.	12 months
Primary	Overall Response Rate (OR) (Partial Response or Better) in Participants With Refractory or Recurrent Glioma	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 brain stem for brain stem lesions. Reported as percentage of participants with partial or better response at 56 days.	56 Days
Secondary	Overall Survival	Percentage of patients alive at one year.	1 year
Secondary	Overall Survival	Percentage of participants alive at 2 years.	up to 17 months