AzTrials
AzTrials

Diffuse Intrinsic Pontine GliomaPhase 1NCT01644773

Study of the Combination of Crizotinib and Dasatinib in Pediatric Research Participants With Diffuse Pontine Glioma (DIPG) and High-Grade Glioma (HGG)

A Phase 1 study testing Crizotinib and Dasatinib in people with Diffuse Intrinsic Pontine Glioma and High-grade Glioma, run by St. Jude Children's Research Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a phase I study to find the highest tolerable dose of crizotinib and dasatinib given in combination to patients with diffuse intrinsic pontine glioma (DIPG) and other types of high grade gliomas (HGG). Participants will receive escalating doses until the highest dose is determined. Read more about this study

Who is it for?
Ages 2 to 21 years
What is being tested?
Crizotinib and Dasatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
1 siteUnited States
Study dates
27 Nov 2012to 28 Sep 2018
Phase
Phase 1
Are there results?
None posted in the registry

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 2 to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Diagnosis of high-grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG). If histologic confirmation was obtained, diagnosis must be one of the following: anaplastic astrocytoma (WHO grade 3), anaplastic oligodendroglioma (WHO grade 3), anaplastic oligoastrocytoma (WHO grade 3), anaplastic ganglioglioma (WHO grade 3), pleomorphic xanthoastrocytoma with anaplastic features (WHO grade 3), malignant glioneuronal tumor, glioblastoma, or gliosarcoma (WHO grade 4)
  • Age > or = 2 years and < or = 21 years
  • Performance score > or = 50 (Lansky for research participants < or = 16 years and Karnofsky for those > 16 years).
  • Adequate organ function at the time of enrollment as follows:
  • Bone marrow: Hemoglobin > or = 8g/dL [may have received packed red blood cell transfusion], absolute neutrophil count (ANC) > or = 1000/mm^3, platelets > or = 100,000/mm^3 [transfusion independent])
  • Renal: Normal serum creatinine based on age as shown below or GFR > 70ml/min/1.73m^2:
Show all 25Show fewer
  • Age < or = 5 years: 0.8 mg/dL maximum
  • Age 5 to 10 years: 1.0 mg/dL maximum
  • Age 10 to 15 years: 1.2 mg/dL maximum
  • Age > 15 years: 1.5 mg/dL maximum
  • Hepatic: SGPT and SGOT < 3x the institutional upper limit of normal (ULN), total bilirubin concentration < 1.5x the institutional ULN, albumin > or = 2g/dL
  • Female research participants > or = 10 years of age or post-menarchal must not be pregnant (confirmed by serum or urine pregnancy test within 1 week of study enrollment) or breastfeeding
  • Female research participants of childbearing age or males research participants of child fathering potential must agree to use safe contraceptive methods for the duration of the study and for 3 months thereafter
  • Diagnosis of recurrent or progressive HGG or DIPG.
  • Neurological deficits must be stable on a fixed or decreasing dose of dexamethasone for ≥7 days before study enrollment.
  • Recovery to ≤ grade 1 from all significant toxicities of previous therapies.
  • Irradiation: Interval from the last dose of local radiation therapy (RT), craniospinal RT, and palliative RT for symptomatic disease > or = 3 months, > or = 6 months, and > or = 2 weeks before study enrollment, respectively
  • Myelosuppressive chemotherapy: Interval > or = 6 weeks and > or = 4 weeks from last dose of nitrosourea and other chemotherapy drugs before study enrollment, respectively. However, interval must be > or = 1 week from last dose of oral etoposide and other drugs administered at low doses (metronomic regimen) before study enrollment
  • Small-Molecule Inhibitors: Interval > or = 1 week from last dose before study enrollment. If a previously used agent has a prolonged half-life, the appropriate interval will be determined after consultation with the principal investigator
  • Monoclonal Antibodies: Interval > or = 3 half-lives before study enrollment. Such cases will need to be discussed with the principal investigator
  • High-Dose Chemotherapy with Stem-Cell Rescue: Interval > or = 3 months before study enrollment
  • Cancer Vaccines and Convection-Enhanced Therapies: Interval > or = 1 month before study enrollment
  • Growth Factors: Interval > or = 1 week and > or = 2 weeks before study enrollment for standard and long-acting growth factors (e.g., pegfilgrastim), respectively
  • Completion of local RT with or without concomitant chemotherapy including temozolomide and radiosensitizing agents (e.g., carboplatin, vorinostat) outside the context of a clinical trial. Any agent administered during RT should have a short half-life so that it should already be completely eliminated by the start of this therapy. If other agents were used concurrently with RT, they will need to be discussed with the principal investigator to assess eligibility
  • Interval > or = 4 weeks and < or = 8 weeks from the completion of radiochemotherapy

Who cannot join

  • Metastatic disease for stratum B only
  • Concomitant use of other anticancer (except for corticosteroids) or experimental agents
  • Use of enzyme-inducing anticonvulsants (EIACs). A minimum interval of 10 days between the last dose of EIAC and start of this therapy will be required for research participants who were previously receiving such medications.
  • Pregnant or lactating patients
  • Research participants with other clinically significant medical disorders that could compromise their ability to tolerate protocol therapy or would interfere with the study procedures or results
  • Prior therapy with a PDGFR or c-Met inhibitor
  • Original treatment design: Body surface area ≥ 1.8m2on dosage levels 3b, 4, and 5
  • Modified treatment design: Body surface area < 0.55 m^2 for all dosage levels

Trial locations and contacts

1 site in 1 country.

United States1 site

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

Other trials in United States

About this study

Official title: Phase I Study of the Combination of Crizotinib and Dasatinib in Pediatric Research Participants With Diffuse Pontine Glioma (DIPG) and High-Grade Glioma (HGG)

This is a phase I study to find the highest tolerable dose of crizotinib and dasatinib given in combination to patients with diffuse intrinsic pontine glioma (DIPG) and other types of high grade gliomas (HGG). Participants will receive escalating doses until the highest dose is determined. Participants will be enrolled in two strata: stratum A for recurrent/ progressive tumors and stratum B for recently diagnosed patients who have completed standard radiation therapy without progressive disease. Up to 7 dosage levels will be tested. Both drugs are taken orally daily, once per day. Correlative pharmacokinetic and biology studies are planned, as well as advanced methods of magnetic resonance imaging (MRI).

Read the detailed description

The Rolling 6 design will be used to estimate the maximum tolerated dose (MTD) and determine the dose-limiting toxicity (DLT) of the combination of escalating doses of crizotinib and dasatinib. Our goal is to accrue research participants for both stratum A and B. However, it is our expectation that the accrual of research participants to stratum B will proceed at a slower pace. Therefore, initially the strategy of dose escalation will be exclusively based on research participants treated at stratum A until the MTD of this combination is reached. Until the MTD of this combination is reached for research participants in stratum A, accrual of research participants in stratum B will be allowed at the highest dosage level which has already been deemed to be safe (i.e., no DLTs in three research participants or ≤ 1 DLT in six research participants). No research participants will be accrued to stratum B until at least one dosage level has been confirmed to be safe in stratum A. Once the MTD for stratum A is reached, we will accrue research participants at this same dosage level to stratum B following the rules of the Rolling 6 design. If the MTD for stratum A is well tolerated among research participants in stratum B, we will proceed with dose escalation for research participants in stratum B based on the same rules of the Rolling 6 design. This strategy is based on the premise that research participants who are more heavily pre-treated (stratum A) may not tolerate therapy as well as those with minimal previous treatment (stratum B).

Primary Objectives:

  • To estimate the MTD of the combination of crizotinib (c-Met and ALK inhibitor) and dasatinib (bcr-abl, PDGFRA and B, src, lck, yes, and c-kit inhibitor) in pediatric research participants with recurrent or progressive DIPG and other HGGs (stratum A).
  • To estimate the MTD of the combination of crizotinib and dasatinib in research participants with DIPG or HGG who completed RT within a short interval prior to enrollment but have not experienced disease progression (stratum B).
Being tested
Crizotinib, Dasatinib
Medical subject headings
Diffuse Intrinsic Pontine Glioma, Glioma

What participants receive

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

  • CrizotinibDrug

    Also called PF-02341066, Xalkori®

    Starting dose level:

    • Initial Treatment Plan: 130 mg/m^2 per dose
    • Modified Treatment Plan per Amendment 1.0: 165 mg/m^2 per dose

    The dose of a single agent will be increased by approximately 30% in each subsequent cohort until the MTD of this combination is reached.

    The doses of each agent will not exceed their single-agent MTD already determined for children with recurrent solid tumors.

    Cycle 1 (28 days): once a day for 28 days

    Cycles 2-26 (28 days each): once a day

  • DasatinibDrug

    Also called BMS-354825, Sprycel®

    Starting dose level: 50 mg/m^2 per dose

    The dose of a single agent will be increased by approximately 30% in each subsequent cohort until the MTD of this combination is reached.

    The doses of each agent will not exceed their single-agent MTD already determined for children with recurrent solid tumors.

    Cycle 1 (28 days): starting on day 3, once a day for 28 days

    Cycles 2-26 (28 days each): once a day

Study groups in NCT01644773
Study groupRoleWhat they receive
ChemotherapyExperimentalResearch participants with high grade glioma or diffuse intrinsic pontine glioma will receive crizotinib and dasatinib.
Receives: Drug: Crizotinib; Drug: Dasatinib

What is being measured

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

  1. Maximum tolerated dose of combination crizotinib and dasatinib in stratum A patients

    Measured: 6 weeks after start of therapy for last enrolled participant

  2. Maximum tolerated dose of combination crizotinib and dasatinib in stratum B patients

    Measured: 6 weeks after start of therapy for last enrolled participant

Timeline

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

  1. First posted19 Jul 2012 (estimated)
  2. Study start27 Nov 2012
  3. Primary completion7 Mar 2018
  4. Study completion28 Sep 2018

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
36 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01644773
Sponsor's protocol ID
SJHG12
Other IDs
NCI-2012-01240
Status last verified
Mar 2019
First submitted
17 Jul 2012
Last updated
22 Mar 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Gibson EG, Campagne O, Selvo NS, Gajjar A, Stewart CF. Population pharmacokinetic analysis of crizotinib in children with progressive/recurrent high-grade and diffuse intrinsic pontine gliomas. Cancer Chemother Pharmacol. 2021 Dec;88(6):1009-1020. doi: 10.1007/s00280-021-04357-4. Epub 2021 Sep 29.

    PubMed 34586478

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Crizotinib and Dasatinib in people with Diffuse Intrinsic Pontine Glioma and High-grade Glioma, run by St. Jude Children's Research Hospital 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 25 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: finished, as of the sponsor's last update on 22 Mar 2019. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Maximum tolerated dose of combination crizotinib and dasatinib in stratum A patients (time frame: 6 weeks after start of therapy for last enrolled participant). The study lists 2 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 NCT01644773, 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 22 Mar 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in