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Diffuse Intrinsic Pontine GliomaPhase 1AflacST1501NCT02644460

Abemaciclib in Children With DIPG or Recurrent/Refractory Solid Tumors

A Phase 1 study testing Abemaciclib in people with Diffuse Intrinsic Pontine Glioma and Brain Tumor, Recurrent, run by Emory University at 4 sites in United States.

Completed

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

Official record
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Trial summary

This is a Phase I clinical trial evaluating abemaciclib (LY2835219), an inhibitor of cyclin dependent-kinases 4 and 6 (Cdk 4/6) in children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG) (Stratum A) and in relapsed/refractory/progressive malignant brain (Grade III/IV, including DIPG… Read more about this study

Who is it for?
Ages 2 to 25 years
What is being tested?
Abemaciclib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
4 sitesUnited States
Study dates
Feb 2016to 10 Oct 2023
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 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patient must have measurable or evaluable disease.
  • Age must be ≥ 2 years and < 25 years
  • Body surface area (BSA) ≥ 0.5 m^2
  • Lansky (for participants ≤ 16 years) or Karnofsky (for participants > 16 years) performance score ≥ 40 at the time of study enrollment
  • Adequate organ function at the time of study enrollment as follows:
  • Bone marrow: Absolute neutrophil count (ANC) ≥ 1,000/μL, platelet count ≥ 75,000/μL (transfusion independent for ≥ 7 days), hemoglobin concentration ≥ 8g/dL (may be transfused)
Show all 30Show fewer
  • Patients with bone marrow metastatic disease who do not meet the above criteria will be eligible to enroll in the study with the following count criteria. These patients will not be evaluable for hematologic toxicity or hematologic DLT.
  • ANC > 750/μL within 7 days prior to first dose of abemaciclib
  • Platelet count > 50,000/μL (may receive platelet transfusions) within 7 days prior to first dose of abemaciclib
  • Hemoglobin ≥ 7.5 g/dL (may receive red blood cell (RBC) transfusions) within 7 days prior to first dose of abemaciclib
  • Renal: Normal serum creatinine concentration based on age or glomerular filtration rate (GFR) > 70 ml/min/1.73m^2
  • Hepatic: Total bilirubin concentration < 1.5x the institutional upper limit of normal for age; serum glutamic pyruvic transaminase (SGPT) < 10x the institutional upper limit of normal for patients on Stratum A. Stratum B patients must have SGPT < 4x the institutional upper limit of normal.
  • Cardiac: Adequate cardiac conductivity with corrected Q-T interval (QTC) of < 450 ms on screening ECG.
  • Female research participants of childbearing age must not be pregnant as confirmed by a serum or urine pregnancy test within 1 week of start of treatment. Participants must not be breast-feeding.
  • All patients should submit an archival tumor biopsy specimen (collected at diagnosis or relapse). Patients who have no tumor tissue available may be permitted to participate after discussion with the principal investigator.
  • Males or females of reproductive potential may not participate unless they have agreed to use two effective contraceptive methods. Abstinence in a non-sexually active child will be sufficient birth control.
  • Diagnosis of DIPG or high-grade glioma originating from the brainstem
  • Participants have had no previous treatment except corticosteroid use.
  • Inclusion Criteria for Stratum B (Recurrent/refractory/progressive MBT (including DIPG) or ST) - Stratum B is closed to further accrual of participants
  • Patients must have radiologic evidence of recurrent, refractory or progressive malignant central nervous system (WHO Grade III or IV) or solid tumor. For patients with radiologic features of DIPG histologic confirmation of diagnosis is not required though biopsy is suggested if clinically indicated.
  • Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration.
  • Patients who are on dexamethasone must be on a stable or decreasing dose for at least one week prior to registration.
  • Patients must have fully recovered from the acute toxic effects of chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
  • Myelosuppressive chemotherapy: Patients must have received their last dose of known myelosuppressive anticancer chemotherapy at least 21 days prior to study registration or at least six weeks if nitrosourea. At least two weeks must have lapsed if patients received lower dose oral etoposide (50 mg/2) without experiencing evidence of myelosuppression (i.e. neutropenia or requiring transfusion with blood products)
  • Biologic agent: Patient must have recovered from any toxicity potentially related to the agent and received their last dose of the biologic agent ≥ 7 days prior to study registration.
  • Monoclonal antibody treatment: At least three half-lives must have elapsed prior to registration.
  • Radiation: Patient has received radiation therapy prior to study registration. Patients must have had their last fraction of local irradiation to the primary tumor ≥ 3 months prior to registration, their last fraction of craniospinal irradiation (>24Gy) or total body irradiation > 3 months prior to registration or > 6 wks for therapeutic doses of metaiodobenzylguanidine (MIBG). Patient has not received focal irradiation for symptomatic metastatic sites within 14 days prior to registration.
  • Bone Marrow Transplant: Patient must be ≥ 3 months since high dose chemotherapy and peripheral blood stem cell rescue prior to registration.
  • Autologous stem cell transplant following myeloablative therapy within 3 months prior to the first dose of abemaciclib or prior allogeneic stem cell transplant at any time. Patients who received stem cell reinfusion following non-myeloablative therapy are eligible once they meet peripheral blood count criteria.
  • Growth factors: Patients must be off all colony forming growth factors(s) for at least 1 week prior to registration (filgrastim, sargramostim, erythropoietin) and at least 2 weeks for long-acting formulations (e.g. Neulasta).

Who cannot join

  • Patients with uncontrolled infection
  • Patients with any concomitant significant medical illness that in the investigator's opinion cannot be adequately controlled with appropriate therapy, or that would impair the evaluation of side effects related to this treatment, alter drug metabolism or the tolerance to this treatment
  • Patients receiving any other anticancer or investigational drug therapy
  • Prior therapy with abemaciclib
  • Known mutation of Rb in tumor tissue
  • Prior history of QTC prolongation or QTC>450 ms on screening ECG.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Children's Healthcare of Atlanta, Egleston

    Atlanta, Georgia, 30322

  • Children's Healthcare of Atlanta, Scottish Rite

    Atlanta, Georgia, 30342

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016

Other trials in United States

About this study

Official title: Abemaciclib in Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma, and in Children With Recurrent and Refractory Solid Tumors Including Malignant Brain Tumors

This is a Phase I clinical trial evaluating abemaciclib (LY2835219), an inhibitor of cyclin dependent-kinases 4 and 6 (Cdk 4/6) in children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG) (Stratum A) and in relapsed/refractory/progressive malignant brain (Grade III/IV, including DIPG; MBT) and solid tumor (ST) patients (Stratum B).

Read the detailed description

Stratum A- Appropriate dose RT will be administered in 30-33 fractions over approximately 6 weeks for Stratum A patients. Treatment with abemaciclib (LY2835219) will start on the same day as radiation therapy (RT) and continue twice daily during and after RT for a maximum treatment duration of 2 years. Investigators plan to treat a maximum of 4 cohorts of research participants (dosage levels 1, 2, 3, and 4) with escalating doses of abemaciclib (LY2835219) starting with dose level 1 (80% of adult dose). A cycle is defined as 28 days and the first 6 weeks of therapy will constitute the dose-limiting toxicity (DLT)-evaluation period. Participants must take abemaciclib by mouth as intact capsules.

Stratum B (no longer enrolling) - Abemaciclib (LY2835219) will be administered orally on a twice daily basis continuously for 28 days, which defines one cycle. The maximum treatment duration will be 2 years. Investigators plan to treat a maximum of 4 cohorts of research participants (dosage levels 1, 2, 3, and 4) with escalating doses of abemaciclib starting with dose level 1 (80% of adult dose). Dose escalation will be independent of Stratum A escalation. A cycle is defined as 28 days and the first 4 weeks of therapy will constitute the DLT-evaluation period. Participants must take abemaciclib by mouth as intact capsules.

Enrollment for Stratum B closed December 27, 2018.

Being tested
Abemaciclib
Medical subject headings
Diffuse Intrinsic Pontine Glioma, Brain Neoplasms, Recurrence, Neuroblastoma, Sarcoma, Ewing, Rhabdomyosarcoma, Osteosarcoma, Rhabdoid Tumor

What participants receive

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

Study groups in NCT02644460
Study groupRoleWhat they receive
Stratum AExperimentalAppropriate dose RT will be administered in 30-33 fractions over approximately 6 weeks for Stratum A patients. Treatment with abemaciclib (LY2835219) will start on the same day as RT and continue twice daily during and after RT for a maximum treatment duration of 2 years. Investigators plan to treat a maximum of 4 cohorts of research participants (dosage levels 1, 2, 3, and 4) with escalating doses of abemaciclib (LY2835219) starting with dose level 1 (80% of adult dose). A cycle is defined as 28 days and the first 6 weeks of therapy will constitute the dose-limiting toxicity (DLT)-evaluation period. Participants must take abemaciclib by mouth as intact capsules.
Receives: Drug: Abemaciclib
Stratum B - enrollment is closed for this study armExperimentalAbemaciclib (LY2835219) will be administered orally on a twice daily basis continuously for 28 days, which defines one cycle. The maximum treatment duration will be 2 years. Investigators plan to treat a maximum of 4 cohorts of research participants (dosage levels 1, 2, 3, and 4) with escalating doses of abemaciclib starting with dose level 1 (80% of adult dose). Dose escalation will be independent of Stratum A escalation. A cycle is defined as 28 days and the first 4 weeks of therapy will constitute the DLT-evaluation period. Participants must take abemaciclib by mouth as intact capsules.
Receives: Drug: Abemaciclib

What is being measured

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

  1. Abemaciclib Maximum Tolerated Dose (MTD) for Diffuse Intrinsic Pontine Glioma (DIPG)

    The maximum dose of abemaciclib tolerated in participants with newly diagnosed diffuse intrinsic pontine glioma (DIPG).

    Measured: Week 6

  2. Abemaciclib Maximum Tolerated Dose (MTD) for Recurrent/Refractory Solid Tumors

    The maximum dose of abemaciclib in participants with recurrent/refractory solid tumors, including malignant tumors of the brain and spine.

    Measured: Week 6

  3. Pharmacokinetics (PK): Predose Concentration (Cmin) of Abemaciclib

    Measured: Cycle 1 to End of Study (up to two years)

  4. Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib

    Measured: Cycle 1 to End of Study (up to two years)

  5. Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Abemaciclib

    Measured: Cycle 1 to End of Study (up to two years)

Secondary outcomes (3)

  1. Number of participants with adverse events

    The number of participants who experience adverse events.

    Measured: End of study (Up to two years)

  2. Number of hematological toxicities

    The number of hematological toxicities observed throughout the study among participants.

    Measured: End of study (Up to two years)

  3. Number of non-hematological toxicities

    The number of non-hematological toxicities observed throughout the study among participants.

    Measured: End of study (Up to two years)

Timeline

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

  1. First posted31 Dec 2015 (estimated)
  2. Study startFeb 2016
  3. Primary completion10 Oct 2023
  4. Study completion10 Oct 2023

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02644460
Sponsor's protocol ID
IRB00083793
Acronym
AflacST1501
Status last verified
Oct 2023
First submitted
15 Dec 2015
Last updated
26 Oct 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

    PubMed 31401903

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Abemaciclib in people with Diffuse Intrinsic Pontine Glioma and Brain Tumor, Recurrent, run by Emory University at 4 sites 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 30 inclusion and 6 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 26 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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?

Abemaciclib Maximum Tolerated Dose (MTD) for Diffuse Intrinsic Pontine Glioma (DIPG) (time frame: Week 6). The study lists 5 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 NCT02644460, 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 26 Oct 2023.

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