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Abemaciclib in Children With DIPG or Recurrent/Refractory Solid Tumors (AflacST1501)

This study is currently recruiting participants.
See Contacts and Locations
Verified July 2017 by Cynthia Wetmore, Emory University
Sponsor:
Information provided by (Responsible Party):
Cynthia Wetmore, Emory University
ClinicalTrials.gov Identifier:
NCT02644460
First received: December 15, 2015
Last updated: July 14, 2017
Last verified: July 2017
  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).

Condition Intervention Phase
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 Drug: Abemaciclib Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Cynthia Wetmore, Emory University:

Primary Outcome Measures:
  • Abemaciclib Maximum Tolerated Dose (MTD) for Diffuse Intrinsic Pontine Glioma (DIPG) [ Time Frame: Week 6 ]
    The maximum dose of abemaciclib tolerated in participants with newly diagnosed diffuse intrinsic pontine glioma (DIPG).

  • Abemaciclib Maximum Tolerated Dose (MTD) for Recurrent/Refractory Solid Tumors [ Time Frame: Week 6 ]
    The maximum dose of abemaciclib in participants with recurrent/refractory solid tumors, including malignant tumors of the brain and spine.

  • Pharmacokinetics (PK): Predose Concentration (Cmin) of Abemaciclib [ Time Frame: Cycle 1 to End of Study (up to two years) ]
  • Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib [ Time Frame: Cycle 1 to End of Study (up to two years) ]
  • Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Abemaciclib [ Time Frame: Cycle 1 to End of Study (up to two years) ]

Secondary Outcome Measures:
  • Number of participants with adverse events [ Time Frame: End of study (Up to two years) ]
    The number of participants who experience adverse events.

  • Number of hematological toxicities [ Time Frame: End of study (Up to two years) ]
    The number of hematological toxicities observed throughout the study among participants.

  • Number of non-hematological toxicities [ Time Frame: End of study (Up to two years) ]
    The number of non-hematological toxicities observed throughout the study among participants.


Estimated Enrollment: 50
Study Start Date: February 2016
Estimated Study Completion Date: October 2020
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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 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.
Drug: Abemaciclib
Other Name: LY2835219
Experimental: 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.
Drug: Abemaciclib
Other Name: LY2835219

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 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.

  Eligibility

Ages Eligible for Study:   2 Years to 25 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Inclusion Criteria - All Participants:

    1. Age must be ≥ 2 and < 21 years
    2. BSA ≥ 0.5 m2
    3. Must have measurable or evaluable disease
    4. Diagnosis of DIPG (Stratum A), or recurrent/refractory/progressive MBT (WHO Grade III/IV) or ST, including neuroblastoma, Ewing sarcoma, rhabdomyosarcoma, malignant rhabdoid tumor and osteosarcoma (Stratum B).
    5. Lansky (for participants ≤ 16 years) or Karnofsky (for participants > 16 years) performance score ≥ 40 at the time of study enrollment
    6. Adequate organ function at the time of study enrollment as follows:
    7. Bone marrow: ANC ≥ 1,000/μL, platelet count ≥ 75,000/μL (transfusion independent meaning not having had platelet transfusion for 7 days prior to enrollment), hemoglobin concentration ≥ 8g/dL (may be transfused). Participants with bone marrow involvement are eligible but not evaluable for hematologic toxicity.
    8. Renal: Normal serum creatinine concentration
    9. Hepatic: Total bilirubin concentration < 1.5x the institutional upper limit of normal for age; SGPT < 3x the institutional upper limit of normal
    10. Female research participants of childbearing potential (age 10 or greater) must not be pregnant as confirmed by a serum or urine pregnancy test and confirmed within 1 week of start of treatment. Participants must not be breast-feeding.
    11. 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 - Stratum A - Newly Diagnosed DIPG

  1. Diagnosis of DIPG or high-grade glioma originating from the brainstem
  2. Participants have had no previous treatment except corticosteroid use.
  3. Participants are able to take abemaciclib as intact capsules by mouth.

Inclusion Criteria - Stratum B - Recurrent/refractory/progressive MBT (including DIPG) or ST

  1. Participants must have radiologic evidence of recurrent, refractory or progressive malignant brain tumor or solid tumor
  2. Participants must be able to swallow capsules.
  3. Participants with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration.
  4. Participants who are on dexamethasone must be on a stable or decreasing dose for at least one week prior to registration.
  5. Participants must have fully recovered from the acute toxic effects of chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
  6. Myelosuppressive chemotherapy: Participants 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 participants received lower dose oral etoposide (50 mg/m2) without experiencing evidence of myelosuppression (i.e. neutropenia or requiring transfusion with blood products)
  7. Biologic agent: Participants 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.
  8. Monoclonal antibody treatment: At least three half-lives must have elapsed prior to registration.
  9. Radiation: Participant has received radiation therapy prior to study registration. Participants 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. Participant has not received focal irradiation for symptomatic metastatic sites within 14 days prior to registration.
  10. Bone Marrow Transplant: Participant must be ≥ 3 months since high dose chemotherapy and peripheral blood stem cell rescue prior to registration.
  11. Growth factors: Participants 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. neupogen).

Exclusion Criteria:

  1. Uncontrolled infection
  2. Prior history of QTc prolongation or QTcF > 450 ms on screening ECG.
  3. Any concomitant significant medical illness that 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
  4. Receiving any other anticancer or investigational drug therapy
  5. Prior therapy with abemaciclib
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02644460

Contacts
Contact: Amy Autry-Bush 404-785-6011 amy.autry-bush@choa.org

Locations
United States, Colorado
Children's Hospital colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Astrid Eder, PhD, CCRP    720-777-8531    astrid.eder@childrenscolorado.org   
Principal Investigator: Margaret Macy, MD         
United States, Georgia
Children's Healthcare of Atlanta, Egleston Recruiting
Atlanta, Georgia, United States, 30322
Contact: Amy Autry-Bush    404-785-6011    amy.autry-bush@choa.org   
Principal Investigator: Cynthia Wetmore, MD, PhD         
Children's Healthcare of Atlanta, Scottish Rite Recruiting
Atlanta, Georgia, United States, 30342
Contact: Amy Autry-Bush    404-785-6011    amy.autry-bush@choa.org   
Principal Investigator: Cynthia Wetmore, MD, PhD         
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Cynthia Wetmore, MD, PhD Children's Healthcare of Atlanta/Emory University
  More Information

Responsible Party: Cynthia Wetmore, Associate Professor, Emory University
ClinicalTrials.gov Identifier: NCT02644460     History of Changes
Other Study ID Numbers: IRB00083793
Study First Received: December 15, 2015
Last Updated: July 14, 2017

Additional relevant MeSH terms:
Neoplasms
Glioma
Brain Neoplasms
Neuroblastoma
Osteosarcoma
Rhabdomyosarcoma
Sarcoma, Ewing
Rhabdoid Tumor
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Sarcoma
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Complex and Mixed

ClinicalTrials.gov processed this record on August 17, 2017