Abemaciclib in Children With DIPG or Recurrent/Refractory Solid Tumors

Study Purpose

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).

Recruitment Criteria

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

Accepts Healthy Volunteers
No

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Study Type
Interventional
Eligible Ages 2 Years - 25 Years
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria for All Participants:

  • - 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) - 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. Inclusion Criteria for Stratum A (Newly Diagnosed DIPG)
  • - 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)
  • - 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).

Exclusion Criteria:

  • - 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 Details

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

Trial ID:
NCT02644460

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase
Phase 1

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Lead Sponsor
Emory University

The person who is responsible for the scientific and technical direction of the entire clinical study.

Principal Investigator
Cynthia Wetmore, MD, PhD
Principal Investigator Affiliation Children's Healthcare of Atlanta/Emory University

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Agency Class
Other
Overall Status Recruiting
Countries United States

The disease, disorder, syndrome, illness, or injury that is being studied.

Conditions
Diffuse Intrinsic Pontine Glioma, Brain Tumor, Recurrent, Solid Tumor, Recurrent, Neuroblastoma, Recurrent, Refractory, Ewing Sarcoma, Recurrent, Refractory, Rhabdomyosarcoma, Recurrent, Refractory, Osteosarcoma, Recurrent, Refractory, Rhabdoid Tumor, Recurrent, Refractory
Additional Details

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

  • - 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.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Atlanta, Georgia

Status

Recruiting

Address

Children's Healthcare of Atlanta, Scottish Rite

Atlanta, Georgia, 30342

Site Contact

Amy Autry-Bush

amy.autry-bush@choa.org

404-785-6011

Atlanta, Georgia

Status

Recruiting

Address

Children's Healthcare of Atlanta, Egleston

Atlanta, Georgia, 30322

Site Contact

Amy Autry-Bush

amy.autry-bush@choa.org

404-785-6011

Children's Hospital colorado, Aurora, Colorado

Status

Recruiting

Address

Children's Hospital colorado

Aurora, Colorado, 80045

Site Contact

Astrid Eder, PhD, CCRP

astrid.eder@childrenscolorado.org

720-777-8531

Phoenix Children's Hospital, Phoenix, Arizona

Status

Recruiting

Address

Phoenix Children's Hospital

Phoenix, Arizona, 85016

Site Contact

Cynthia Wetmore, MD, PhD

cwetmore@phoenixchildrens.com

602-933-0920

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