GliomaPhase 2NCT03352427

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

A Phase 2 study testing Dasatinib and Everolimus in people with Glioma and High Grade Glioma, run by University of Michigan Rogel Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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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… Read more about this study

Who is it for?: Ages 1 year to 50 years
Conditions the study is for: Glioma, High Grade Glioma, Pontine Tumors
What is being tested?: Dasatinib and Everolimus
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 3 participants
Where: 1 siteUnited States
Study dates: 6 Dec 2017to 15 May 2019
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 1 year to 50 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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.

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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.

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Michigan Cancer Center
Ann Arbor, Michigan, 48109

Other trials in United States

About this study

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

Conditions: Glioma, High Grade Glioma, Pontine Tumors
Being tested: Dasatinib, Everolimus
Medical subject headings: Glioma, Brain Stem Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DasatinibDrug
60 mg/m2 orally twice daily
EverolimusDrug
3.0 mg/m2, with titration of dosing after first cycle to keep trough level of 5-15 ug/ml

Study groups in NCT03352427
Study group	Role	What they receive
Dasatinib+Everolimus	Experimental	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. Receives: Drug: Dasatinib; Drug: Everolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 8 months
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.
Measured: 12 months
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.
Measured: 56 Days

Secondary outcomes (2)

Overall Survival
Percentage of patients alive at one year.
Measured: 1 year
Overall Survival
Percentage of participants alive at 2 years.
Measured: up to 17 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Dec 201715 May 2019

First posted24 Nov 2017
Study start6 Dec 2017
Primary completion17 Apr 2019
Study completion15 May 2019

Why it stopped: Low accrual

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for GliomaStudies of the same condition, open and under way.
More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 3 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03352427
Sponsor's protocol ID: UMCC 2017.042
Other IDs: HUM00123094
Status last verified: Sep 2022
First submitted: 20 Nov 2017
Last updated: 5 Oct 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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, Glasser C, Leary SE, Venneti S, Kumar-Sinha C, Chinnaiyan AM, Mody R, Pai MP, Phoenix TN, Marini BL, Koschmann C. Everolimus improves the efficacy of dasatinib in PDGFRalpha-driven glioma. J Clin Invest. 2020 Oct 1;130(10):5313-5325. doi: 10.1172/JCI133310.
PubMed 32603316

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
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All Glioma trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2 Study of Dasatinib in Combination With Everolimus for Children With Gliomas Harboring PDGFR Alterations
ClinicalTrials.gov ID: NCT03352427
Acronym / sponsor ID: UMCC 2017.042
Conditions: Glioma, High Grade Glioma, Pontine Tumors
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Low accrual
Enrolment: 3 participants (actual)
Lead sponsor: University of Michigan Rogel Cancer CenterUniversity, hospital or other
Study start: 6 Dec 2017 (actual)
Primary completion: 17 Apr 2019 (actual)
Study completion: 15 May 2019 (actual)
First posted: 24 Nov 2017 (actual)
Results: Posted 5 Oct 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Dasatinib+Everolimus	Experimental	Drug: Dasatinib, Drug: EverolimusDasatinib = 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.

Who may qualify

Ages: 1 year to 50 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (22 listed)

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

Key exclusion criteria (8 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Dasatinib60 mg/m2 orally twice daily	Drug	Dasatinib+Everolimus
Everolimus3.0 mg/m2, with titration of dosing after first cycle to keep trough level of 5-15 ug/ml	Drug	Dasatinib+Everolimus

Primary outcome

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 brain stem for brain stem lesions. Reported as percentage of participants with partial or better response at 56 days.

2 secondary outcomes

Overall Survival
Time frame: 1 year
Overall Survival
Time frame: up to 17 months

Results and safety

Results posted to the registry on 5 Oct 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dasatinib+Everolimus	3	3

Primary outcome: Progression-free Survival in Participants With Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG)

Time frame: 8 months. Number. Unit: percentage of participants

Measure	Dasatinib+Everolimus n = 3
Value	0

Primary outcome: Progression-free Survival in Participants With Newly Diagnosed High-grade Glioma (HGG)

Time frame: 12 months. Number. Unit: percentage of participants

Measure	Dasatinib+Everolimus n = 3
Value	0

Primary outcome: Overall Response Rate (OR) (Partial Response or Better) in Participants With Refractory or Recurrent Glioma

Time frame: 56 Days. Number. Unit: percentage of participants

Measure	Dasatinib+Everolimus n = 3
Value	0

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected up to 30 days after the last dose of study treatment (total of 17 months; average of 4 months). All cause mortality occurred any time during the study (range from 4 - 17 months).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dasatinib+Everolimus	1 of 3 (33.3%)	3 of 3 (100%)	3 of 3

Limitations and caveats (from the sponsor): Trial enrollment was limited due to requirement for patient insurance coverage for all aspects of treatment. Due to limited sample size, full statistical analysis isn't possible. Descriptive results of this cohort compiled with data available from patients treated locally with a similar treatment plan is available in the following publication: Miklja et al, JCI, 2020 \[PMID: 32603316\].

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 32603316Miklja 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, Glasser C, Leary SE, Venneti S, Kumar-Sinha C, Chinnaiyan AM, Mody R, Pai MP, Phoenix TN, Marini BL, Koschmann C. Everolimus improves the efficacy of dasatinib in PDGFRalpha-driven glioma. J Clin Invest. 2020 Oct 1;130(10):5313-5325. doi: 10.1172/JCI133310.
Individual participant dataSharing planned: No

Related trials for Glioma

Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
Low Grade Astrocytoma, Low Grade Glioma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Carl Koschmann, M.D. principal investigator

University of Michigan Rogel Cancer Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dasatinib and Everolimus in people with Glioma and High Grade Glioma, run by University of Michigan Rogel Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 5 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival in Participants With Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) (time frame: 8 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03352427, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2022.