E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Castration-Resistant Prostate Cancer |
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E.1.1.1 | Medical condition in easily understood language |
Prostate cancer that has spread beyond the prostate and that keeps growing despite castration |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10076506 |
E.1.2 | Term | Castration-resistant prostate cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To characterize the efficacy of abemaciclib monotherapy. |
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E.2.2 | Secondary objectives of the trial |
To further characterise the clinical activity of abemaciclib monotherapy. To characterise the safety profile of abemaciclib. To explore patient reported tolerability of abemaciclib monotherapy (including symptomatic AEs and overall side-effect burden), patient reported pain intensity, physical functioning, and overall health related quality of life. To characterise the PK of abemaciclib and its metabolites. To characterise Ki-67 baseline expression. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Participant must have metastatic prostate cancer for which castration (medical or surgical) is no longer effective (castration-resistant). • Participant must have disease spread to soft tissue that is measurable. • Participant must have documented evidence of progressive disease by PSA test or imaging. • Participant must have previously received at least one of the following treatment: abiraterone acetate, apalutamide, darolutamide or enzalutamide. • Participant must have previously received chemotherapy with docetaxel and cabazitaxel. • Participant must be willing and amenable to undergo a biopsy of tumor tissue (or able to provide adequate archived tumor tissue sample) and to provide blood for research. • Participant must have good physical functioning ability and adequate organ function.
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E.4 | Principal exclusion criteria |
• Participant must not have received more than 3 therapy regimens for metastatic castration-resistant prostate cancer (NOTE: GnRHa, first-generation antiandrogens (flutamide, nilutamide, or bicalutamide), diethylstilbestrol (DES) (or other estrogens), corticosteroids, ketoconazole, and bone loss-prevention will not count as systemic therapy regimens. • Participants must not have previously received abemaciclib or any cyclin-dependent kinase (CDK)4 and/or CDK6 inhibitors. • Participants must not have serious and/or uncontrolled preexisting medical condition(s) including but not limited to severe renal impairment, severe hepatic impairment, interstitial lung disease (ILD)/pneumonitis, severe dyspnea at rest or requiring oxygen therapy or other serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study. • Participants must not have, or suspected to have, brain metastasis. • Participants must not have untreated spinal cord compression, evidence of spinal metastases with risk of spinal compression or structurally unstable bone lesions suggesting impending fracture.
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective Response Rate (ORR) per RECIST 1.1: Percentage of Participants with Best Response of Complete Response (CR) or Partial Response (PR) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Radiologic assessment every 8 weeks and within 14 days of symptomatic progression if no radiographic progression yet and prior to the start of new anticancer therapy, palliative radiotherapy or surgery. |
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E.5.2 | Secondary end point(s) |
Radiographic Progression-Free Survival (rPFS) Overall Survival (OS) Duration of Response (DOR) Disease Control Rate (DCR) Prostate Specific Antigen (PSA) Response Rate Time to PSA progression Time to symptomatic progression Patient-Reported Outcomes (PRO) Pharmacokinetics (PK): Mean Steady State Concentration of Abemaciclib and its Metabolites Percentage of Ki-67 Positive Cells by Immunohistochemistry (IHC) Assessment of safety including, but not limited to, the following: AEs, SAEs, physical examination, and clinical laboratory abnormalities per CTCAE v5.0
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety evaluations will occur at each study visit and throughout the study. Radiologic assessment every 8 weeks and within 14 days of symptomatic progression if no radiographic progression yet and prior to the start of new anticancer therapy, palliative radiotherapy or surgery. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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This study will be considered complete (that is, scientific evaluation will be complete [study completion] following the evaluation of all primary and secondary endpoints, as determined by Lilly. Investigators will continue to follow the study schedule for all participants until notified by Lilly that study completion has occurred. “End of Study” refers to the date of the last visit or last scheduled procedure for the last participant. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |