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A Study of Abemaciclib (LY2835219) in Combination With Temozolomide and Irinotecan and Abemaciclib in Combination With Temozolomide in Children and Young Adult Participants With Solid Tumors

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ClinicalTrials.gov Identifier: NCT04238819
Recruitment Status : Recruiting
First Posted : January 23, 2020
Last Update Posted : April 9, 2021
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Brief Summary:
The study's purpose is to see if the drug abemaciclib is safe and effective in combination with temozolomide and irinotecan (Part A) and abemaciclib in combination with temozolomide (Part B) in pediatric and young adult participants with relapsed/refractory solid tumors.

Condition or disease Intervention/treatment Phase
Relapsed Solid Tumor Refractory Solid Tumor Drug: Abemaciclib Drug: Irinotecan Drug: Temozolomide Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Dose Escalation Study of Abemaciclib in Combination With Temozolomide and Irinotecan (Part A) and Abemaciclib in Combination With Temozolomide (Part B) in Pediatric and Young Adult Patients With Relapsed/Refractory Solid Tumors
Actual Study Start Date : November 9, 2020
Estimated Primary Completion Date : May 5, 2022
Estimated Study Completion Date : January 31, 2023


Arm Intervention/treatment
Experimental: Dose Escalation: Abemaciclib + Irinotecan + Temozolomide
Abemaciclib given orally, irinotecan given intravenously (IV) and temozolomide given orally.
Drug: Abemaciclib
Administered orally
Other Name: LY2835219

Drug: Irinotecan
Administered IV

Drug: Temozolomide
Administered orally

Experimental: Dose Expansion: Abemaciclib + Irinotecan + Temozolomide
Abemaciclib given orally, irinotecan given IV and temozolomide given orally.
Drug: Abemaciclib
Administered orally
Other Name: LY2835219

Drug: Irinotecan
Administered IV

Drug: Temozolomide
Administered orally

Experimental: Dose Escalation: Abemaciclib + Temozolomide
Abemaciclib and temozolomide given orally.
Drug: Abemaciclib
Administered orally
Other Name: LY2835219

Drug: Temozolomide
Administered orally

Experimental: Dose Expansion: Abemaciclib + Temozolomide
Abemaciclib and temozolomide given orally.
Drug: Abemaciclib
Administered orally
Other Name: LY2835219

Drug: Temozolomide
Administered orally




Primary Outcome Measures :
  1. Number or Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: Cycle 1 (21 Day Cycle) ]
    Number of Participants with DLTs

  2. Pharmacokinetics (PK): Mean Steady State Concentrations of Abemaciclib [ Time Frame: Cycle 1 through Cycle 3 (21 Day Cycle) ]
    PK: Mean Steady State Concentrations of Abemaciclib

  3. PK: Mean Steady State Concentrations of Irinotecan [ Time Frame: Cycle 1 through Cycle 3 (21 Day Cycle) ]
    PK: Mean Steady State Concentrations of Irinotecan

  4. PK: Mean Steady State Concentrations of Temozolomide [ Time Frame: Cycle 1 through Cycle 3 (21 Day Cycle) ]
    PK: Mean Steady State Concentrations of Temozolomide


Secondary Outcome Measures :
  1. Overall Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR) or Partial Response (PR) [ Time Frame: Baseline through Disease Progression or Death (Estimated up to 24 Months) ]
    ORR: Percentage of Participants with Best Response of CR or PR

  2. Duration of Response (DoR) [ Time Frame: Date of First Evidence of a CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Estimated up to 24 Months) ]
    DoR

  3. Clinical Benefit Rate (CBR): Percentage of Participants With Best Overall Response of CR, PR or SD With a Duration of At Least 6 Months [ Time Frame: Baseline through Disease Progression or Death Due to Any Cause (Estimated up to 24 Months) ]
    CBR: Percentage of Participants With Best Overall Response of CR, PR or SD With a Duration of At Least 6 Months

  4. Disease Control Rate (DCR): Percentage of Participants with a Best Overall Response of CR, PR, and Stable Disease (SD) [ Time Frame: Baseline through Measured Progressive Disease (Estimated up to 24 Months) ]
    DCR: Percentage of Participants with a Best Overall Response of CR, PR, and SD

  5. Acceptability Questionnaire [ Time Frame: Cycle 2 Day 1 (21 Day Cycles) ]
    Participants were evaluated for abemaciclib acceptability (palatability and ease of administration) using a 5-category questionnaire. Participants were asked to answer one of the following to describe the acceptability of abemaciclib: Very difficult, difficult, neither easy nor difficult, easy, or very easy.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Body weight ≥10 kilograms and body surface area (BSA) ≥0.5 meters squared.
  • Participants with any relapsed/refractory malignant solid tumor (excluding lymphoma), including central nervous system tumors, that have progressed on standard therapies and, in the judgment of the investigator, are appropriate candidates for the experimental therapy combination in the study part that is currently enrolling.

    • Participants must have at least one measurable (per Response Criteria in Solid Tumors [RECIST v1.1; [Eisenhauer et al. 2009] or Response Assessment in Neuro-Oncology (RANO) for central nervous system (CNS) tumors [Wen et al. 2010]) or evaluable lesion.
    • Participants must have had histologic verification of malignancy at original diagnosis or relapse, except:

      • Participants with extra-cranial germ-cell tumors who have elevations of serum tumor markers including alpha-fetoprotein or beta- human chorionic gonadotropin (HCG).
      • Participants with intrinsic brain stem tumors or participants with CNS-germ cell tumors and elevations of CSF or serum tumor markers including alpha-fetoprotein or beta-HCG.
  • A Lansky score ≥50 for participants ≤16 years of age or Karnofsky score ≥50 for participants >16 years of age.
  • Participants must have discontinued all previous treatments for cancer or investigational agents and must have recovered from the acute effects to Grade ≤1 at the time of enrollment.
  • Able to swallow.
  • Adequate hematologic and organ function ≤2 weeks (14 days) prior to first dose of study drug.
  • Females of reproductive potential must have negative serum pregnancy test at baseline (within 7 days prior to starting treatment).
  • Both female and male participants of reproductive potential must agree to use highly effective contraceptive precautions (and avoid sperm donation for males) during the trial. For abemaciclib, females should use contraception for at least 3 weeks following the last abemaciclib dose (males have no restriction for contraceptive use following treatment with abemaciclib). For other study drugs, highly effective contraceptive precautions (and avoiding sperm donation) must be used according to their label.
  • Life expectancy of at least 8 weeks and able to complete at least 1 cycle of treatment.
  • Caregivers and participants willing to make themselves available for the duration of the trial.

Exclusion Criteria:

  • Received allogenic bone marrow or solid organ transplant.
  • Received live vaccination (within 4 weeks prior to starting study treatment).
  • Have a personal history of any of the following conditions within the last 12 months: syncope of cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest.
  • Intolerability or hypersensitivity to any of the study treatments or its components.
  • Diagnosed and/or treated additional malignancy within 3 years prior to enrollment that may affect the interpretation of results, with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or curatively resected in situ cervical and/or breast cancers.
  • Pregnant or breastfeeding.
  • Active systemic infections or viral load.
  • Serious and/or uncontrolled preexisting medical condition(s) that would preclude participation in this study.
  • Have a bowel obstruction (Part A of this study only).
  • Treated with drugs known to be strong inhibitors or inducers of isoenzyme cytochrome P450 3A (CYP3A) or strong inhibitors of uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) if the treatment cannot be discontinued or switched to a different medication at least 5 half-lives prior to starting study drug.
  • Received prior treatment with cyclin-dependent kinase (CDK) 4 & 6 inhibitor.
  • Currently enrolled in any other clinical study involving an investigational product or non-approved use of a drug or device.
  • Has received an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer.
  • Tumor contains known somatic or germline retinoblastoma (RB) mutation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04238819


Contacts
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Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Clinicaltrials.gov@lilly.com

Locations
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United States, Arizona
Phoenix Childrens Hospital Not yet recruiting
Phoenix, Arizona, United States, 85016
Contact    602-406-2141      
Principal Investigator: Lindsey M Hoffman         
United States, Minnesota
University of Minnesota Hospital Not yet recruiting
Minneapolis, Minnesota, United States, 55455
Contact    612-626-3593      
Principal Investigator: Emily Greengard         
United States, Pennsylvania
Children's Hospital of Philadelphia Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact    267-426-5414      
Principal Investigator: Frank M Balis         
Belgium
UZ-Gent Recruiting
Gent, Belgium, 9000
Contact    003293324812      
Principal Investigator: Bram De Wilde         
France
Centre Leon Berard Recruiting
Lyon CEDEX 08, Rhône-Alpes, France, 69373
Contact    0033469166550      
Principal Investigator: Pierre LEBLOND         
Institut Curie Recruiting
Paris, France, 75248
Contact    00330144324270      
Principal Investigator: Isabelle Aerts         
Gustave Roussy Recruiting
Villejuif Cedex, France, 94805
Contact    0033142114661      
Principal Investigator: Birgit Geoerger         
Germany
Charité Universitätsmedizin Berlin Campus Buch Recruiting
Berlin, Germany, 13353
Contact    004930450666658      
Principal Investigator: Johannes Schulte         
Universtitätsklinikum Essen AöR Not yet recruiting
Essen, Germany, 45147
Contact    00492017233784      
Principal Investigator: Dirk Reinhardt         
Hopp-Kindertumorzentrum Heidelberg (KiTZ) Recruiting
Heidelberg, Germany, 69120
Contact    00496221424585      
Principal Investigator: Kristian Pajtler         
Italy
Policlinico Univ. Agostino Gemelli Not yet recruiting
Roma, Italy, 00168
Contact    00390630155556      
Principal Investigator: Antonio Ruggiero         
Japan
National Cancer Center Hospital Recruiting
Chuo-ku, Tokyo, Japan, 104-0045
Contact    81120023812      
Principal Investigator: Chitose Ogawa         
Spain
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Contact    0034934893093      
Principal Investigator: Lucas Moreno         
Hospital Infantil Universitario Niño Jesús Recruiting
Madrid, Spain, 28009
Contact    0034915035900      
Principal Investigator: Álvaro Lassaletta Atienza         
Hospital Universitario La Fe de Valencia Recruiting
Valencia, Spain, 46026
Contact    0034961244000-411532      
Principal Investigator: Antonio Juan         
Sponsors and Collaborators
Eli Lilly and Company
Investigators
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Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
Additional Information:
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Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT04238819    
Other Study ID Numbers: 16950
I3Y-MC-JPCS ( Other Identifier: Eli Lilly and Company )
2019-002931-27 ( EudraCT Number )
First Posted: January 23, 2020    Key Record Dates
Last Update Posted: April 9, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Eli Lilly and Company:
CDK4
CDK6
Ewing's sarcoma
Neuroblastoma
Malignant rhabdoid tumor
Rhabdomyosarcoma
Osteosarcoma
Brain tumor
Glioblastoma
Malignant glioma
Diffuse intrinsic pontine glioma
Medulloblastoma
Ependymoma
Solid tumor
High-grade glioma
Additional relevant MeSH terms:
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Neoplasms
Irinotecan
Temozolomide
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents