E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Previously Treated Hormone Receptor-Positive, HER2-Negative, Metastatic Breast Cancer |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10006187 |
E.1.2 | Term | Breast cancer |
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 evaluate and summarize incidence of severe diarrhea (≥Grade 3) or prolonged Grade 2 diarrhea (defined as >7 days duration), including the incidence of dose reductions, dose interruptions, and/or treatment discontinuations due to severe diarrhea or prolonged Grade 2 diarrhea over the first 3 cycles when abemaciclib is administered: • with a meal • without a meal, taken in the modified fasted condition • without regard to food
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E.2.2 | Secondary objectives of the trial |
To assess safety and toxicity profile of abemaciclib To evaluate the PK parameters of abemaciclib and its metabolites
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Protocol Addendum I3Y-MC-JPCP(2): An Open-Label, Randomized Phase 2 Study of the Impact of Food on Tolerability when Receiving Abemaciclib for Patients with Previously Treated Hormone Receptor-Positive, HER2-Negative, Metastatic Breast Cancer. Protocol Addendum 2: Approval Date: 19 July 2018
This protocol addendum describes the acquisition of biological samples (fresh human tumor tissue and blood) from approximately 10 to 20 patients who will be participating in clinical trial I3Y-MC-JPCP (JPCP) for the analysis of biomarkers.
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E.3 | Principal inclusion criteria |
Have a diagnosis of HR+, HER2− mBC Have all of the following: • Recurrent, locally advanced, unresectable or mBC with disease progression following anti-estrogen therapy. • Prior treatment with chemotherapy for locally advanced or metastatic disease. • No prior treatment with CDK4 and CDK6 inhibitor.
Have a performance status (PS) of ≤1 on the Eastern Cooperative Oncology Group (ECOG) scale (Oken et al. 1982)
Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures, including keeping records in the electronic patient diary (e-diary) as required by study protocol.
Have discontinued all previous treatments for cancer and recovered from the acute effects of therapy. All patients who experienced diarrhea as a side effect of previous therapy must have recovered to ≤Grade 1 prior to enrollment. |
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E.4 | Principal exclusion criteria |
Patients will be excluded from the study if they meet any of the following criteria: are currently receiving treatment in a clinical study involving an investigational product or are enrolled into any other type of medical research judged not to be scientifically or medically compatible with this study. have a serious concomitant systemic disorder (for example, active infection or a GI disorder causing clinically significant symptoms such as nausea, vomiting or diarrhea [such as Crohn’s disease, ulcerative colitis], or profound immune suppression) or a serious preexisting medical condition (for example, history of major surgical resection involving the stomach or small bowel) that, in the opinion of the investigator, would compromise/preclude the patient’s ability to adhere to the protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Incidence of severe diarrhea (≥Grade 3) • Incidence of prolonged Grade 2 diarrhea (defined as >7 days duration) • Dose reductions due to diarrhea • Dose interruptions due to diarrhea • Treatment discontinuations due to diarrhea • Utilization of antidiarrheals
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Patients will record daily information on the number of stools, diarrhea, use of loperamide and the timing of the abemaciclib intake relative to their meals in cycle 1-3. Dose reductions and medications will be evalutaed throughout the study by the investigators. |
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E.5.2 | Secondary end point(s) |
The safety endpoints evaluated will include, but are not limited to, the following: • Overall safety • incidence and severity of TEAEs, SAEs, deaths, and clinical laboratory abnormalities Steady state concentrations of abemaciclib and its metabolites LSN2839567 and LSN3106726
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
AE collection throughout study
PK in cycles 1-3 |
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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 | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
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 | Yes |
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 | 3 |
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 | 5 |
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 |
Australia |
Belgium |
Russian Federation |
Spain |
Turkey |
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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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End of the study is the date of the last visit or last scheduled procedure for the last patient. |
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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 | 4 |
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 | 4 |