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

Sponsor

Eli Lilly and Company (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04238819

Collaborator

(none)

Enrollment

Locations

Arms

95.7

Anticipated Duration (Months)

2.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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

Study Design

Study Type:

Interventional

Anticipated 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 :

Nov 9, 2020

Anticipated Primary Completion Date :

Jun 30, 2027

Anticipated Study Completion Date :

Oct 30, 2028

Arms and Interventions

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 Names: 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 Names: LY2835219 Drug: Irinotecan Administered IV Drug: Temozolomide Administered orally
Experimental: Dose Escalation: Abemaciclib + Temozolomide Abemaciclib and temozolomide given orally.	Drug: Abemaciclib Administered orally Other Names: LY2835219 Drug: Temozolomide Administered orally
Experimental: Dose Expansion: Abemaciclib + Temozolomide Abemaciclib and temozolomide given orally.	Drug: Abemaciclib Administered orally Other Names: LY2835219 Drug: Temozolomide Administered orally

Outcome Measures

Primary Outcome Measures

Number or Participants with Dose Limiting Toxicities (DLTs) [Cycle 1 (21 Day Cycle)]
Number of Participants with DLTs
Pharmacokinetics (PK): Mean Steady State Concentrations of Abemaciclib [Cycle 1 through Cycle 3 (21 Day Cycle)]
PK: Mean Steady State Concentrations of Abemaciclib
PK: Mean Steady State Concentrations of Irinotecan [Cycle 1 through Cycle 3 (21 Day Cycle)]
PK: Mean Steady State Concentrations of Irinotecan
PK: Mean Steady State Concentrations of Temozolomide [Cycle 1 through Cycle 3 (21 Day Cycle)]
PK: Mean Steady State Concentrations of Temozolomide

Secondary Outcome Measures

Overall Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR) or Partial Response (PR) [Baseline through Disease Progression or Death (Estimated up to 24 Months)]
ORR: Percentage of Participants with Best Response of CR or PR
Duration of Response (DoR) [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
Clinical Benefit Rate (CBR): Percentage of Participants With Best Overall Response of CR, PR or SD With a Duration of At Least 6 Months [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
Disease Control Rate (DCR): Percentage of Participants with a Best Overall Response of CR, PR, and Stable Disease (SD) [Baseline through Measured Progressive Disease (Estimated up to 24 Months)]
DCR: Percentage of Participants with a Best Overall Response of CR, PR, and SD
Acceptability Questionnaire [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Phoenix Children's Hospital	Phoenix	Arizona	United States	85016
2	The Regents of the University of California - Los Angeles (UCLA Pediatrics)	Los Angeles	California	United States	90095-1752
3	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
4	University of Minnesota Hospital	Minneapolis	Minnesota	United States	55455
5	Cohen Children's Medical Center	New Hyde Park	New York	United States	11040
6	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
7	Lifespan Cancer Institute	Providence	Rhode Island	United States	02906
8	University of Texas Southwestern Medical Center at Dallas	Dallas	Texas	United States	75235
9	Cook Children's Hospital	Fort Worth	Texas	United States	76104
10	UZ-Gent	Gent		Belgium	9000
11	Centre Leon Berard	Lyon	Rhône-Alpes	France	69008
12	Institut Curie	Paris		France	75248
13	Gustave Roussy	Villejuif Cedex		France	94805
14	Charité Campus Virchow-Klinikum	Berlin		Germany	13353
15	Universtitätsklinikum Essen AöR	Essen		Germany	45147
16	Hopp-Kindertumorzentrum Heidelberg (KiTZ)	Heidelberg		Germany	69120
17	Policlinico Gemelli - Università Cattolica del Sacro Cuore	Roma		Italy	00168
18	National Cancer Center Hospital	Chuo-ku	Tokyo	Japan	104-0045
19	Hospital Universitari Vall d'Hebron	Barcelona	Barcelona [Barcelona]	Spain	8035
20	Hospital Infantil Universitario Niño Jesús	Madrid	Madrid, Comunidad De	Spain	28009
21	Hospital Universitario La Fe de Valencia	Valencia		Spain	46026

Sponsors and Collaborators

Eli Lilly and Company

Investigators

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