A Phase 1b Study of Abemaciclib Plus Chemotherapy in Pediatric and Young Adult Patients with Relapsed/Refractory Solid Tumors
- Conditions
- Pediatric and Young Adult Patients Relapsed/Refractory Solid TumorsMedDRA version: 20.0Level: PTClassification code 10015560Term: Ewing's sarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10039022Term: RhabdomyosarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10029260Term: NeuroblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: LLTClassification code 10073335Term: Rhabdoid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10031291Term: OsteosarcomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10018336Term: GlioblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10065443Term: Malignant gliomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: PTClassification code 10027107Term: MedulloblastomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-002931-27-IT
- Lead Sponsor
- ELI LILLY & COMPANY, LILLY CORPORATE CENTER
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 60
- Participants must be =18 years of age at the time of study enrollment
- Body weight =10 kilograms and body surface area (BSA) =0.5 meters squared.
- Participants with any relapsed/refractory 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.
- A Lansky score =50 for participants =16 years of age, and 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 intact capsules.
- 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 are willing to make themselves available for the duration of the trial.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
- Received allogenic bone marrow or solid organ transplant.
- Received live vaccination (within 4 weeks prior to starting study treatment).
- Participants with psychiatric illness/social situation that, in the opinion of the investigator, could cause unacceptable safety risks or compromise compliance with the protocol.
- 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 relevant to the study part that is currently enrolling or a known hypersensitivity to dacarbazine.
- 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 (such as severe renal impairment, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, history of major surgical resection involving the stomach or small bowel, or preexisting Crohn’s disease or ulcerative colitis or a preexisting chronic condition resulting in clinically significant diarrhea).
- Treated with drugs known to be strong inhibitors or inducers of isoenzyme cytochrome P450 3A (CYP3A) or strong inhibitors of 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 RB (retinoblastoma) mutation. Screening is not required for enrollment.
-Participants with a bowel obstruction will be excluded from Part A of this study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To determine the optimal RP2D for abemaciclib in patients with relapsed/refractory solid tumors:<br>- in combination with irinotecan and<br>temozolomide (Part A) <br>- in combination with temozolomide (Part B);Secondary Objective: To characterize the safety profile of abemaciclib in Parts A and B<br>To document the preliminary anti-tumor activity per RECIST v1.1 of abemaciclib in Parts A and B<br>To assess the acceptability and palatability of the age-appropriate dispersed tablets;Primary end point(s): - Dose Limiting Toxicity (DLT)<br>- Maximum Tolerated Doses (MTD)<br>- PK (plasma concentrations of abemaciclib, irinotecan, and temozolomide);Timepoint(s) of evaluation of this end point: - Number of Participants with DLTs in Cycle 1.<br>- Mean Steady State Concentrations of Abemaciclib, Irinotecan and Temozolomide from Cycle 1 through Cycle 3 (21 Day Cycle)]
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Safety (including but not limited to):TEAEs, SAEs, deaths<br>- Clinical laboratory abnormalities per CTCAE (version 5.0), vital signs, and physical examinations<br>- Dose modifications of all study drugs<br>- Overall Response Rate (ORR)<br>- Duration of Response (DoR)<br>- Clinical Benefit Rate (CBR)<br>- Disease Control Rate (DCR)<br>- Assessment of tablet or oral suspension product acceptability and palatability;Timepoint(s) of evaluation of this end point: - ORR: Percentage of Participants with Best Response of CR or PR<br>- The DoR is measured from the date of first evidence of a CR or PR to the date of objective<br>progression or the date of death due to any cause, whichever is earlier.<br>- The DCR is the percentage of patients with a best response of CR, PR, or stable disease.<br>- The CBR is the percentage of patients with a best response of CR or PR, or stable disease for at least 6 months.<br>- Acceptability and Palatability: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1