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

• Status: Recruiting
• Trial end date: 2023-12-21
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Eli Lilly and Company
• Treatments: Irinotecan; Temozolomide

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.