E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hormone receptor positive, Her2 positive advanced 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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to compare the efficacy of abemaciclib plus trastuzumab plus fulvestrant and abemaciclib plus trastuzumab to standard-of-care single-agent chemotherapy of physician’s choice plus trastuzumab with respect to progression free survival (PFS).
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E.2.2 | Secondary objectives of the trial |
To review overall survival, objective response rate, duration of response, disease control rate, clinical benefit rate, safety and tolerability of abemaciclib, treatment impact on pain, disease symptoms and overall quality of life, pharmacokinetics of abemaciclib and relationship between abeamciclib, trastuzumab and fulvestrant exposure and clinical outcomes |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Have diagnosis of HR+, HER2+ metastatic breast cancer on the primary tumor or metastatic lesion
2. Have unresectable locally advanced recurrent breast cancer or metastatic breast cancer
3. Have adequate tumor tissue available and collected prior to randomization
4. Have previously received at least two HER2 directed therapies for advanced disease
5. Must have received trastuzumab emtansine (TDM1) in any disease setting
6. Must have received a taxane in any disease setting
7. Have discontinued all previous therapies for cancer (except trastuzumab) for at least 21 days for myelosuppressive agents or 14 days for non-myelosupprevice agents
8. Have postmenopausal status
9. Have performance status of 0 to 1 on the ECOG scale
10. Must have LVEF of 50% or higher at baseline |
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E.4 | Principal exclusion criteria |
1. Have visceral crisis
2. Known CNS metastases that are untreated, symptomatic or require steroids to control symptoms
3. Received prior treatment with any CDK4 or CDK6 inhibitor
4. Have had major surgery within 14 days prior to randomization
5. Received treatment with a drug that has not received regulatory approval for any indication within 14 to 21 days of randomization for non-myelosuppressive or non-myelosupprevice agent, respectively
6. Have serious preexisting medical conditions that would preclude participation in this study
7. Have a history within the last 6 months of symptomatic congestive heart failure, myocardial infarction or unstable angina
8. Have a personal history within the last 12 months of any of the following conditions: syncope of cardiovascular etiology, ventricular tachycardia, ventricular fibrillation or sudden cardiac arrest |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
One planned primary analysis for PFS performed after 165 events have been observed. Within 28 days of randomization, baseline tumor assessment will be performed for each patient. Repeat scans will be done every 6 weeks for 36 weeks from first dose of therapy, then every 9 weeks and within 14 days of clinical progression. |
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E.5.2 | Secondary end point(s) |
OS rate, ORR, DoR, disease control., clinical benefit rate, safety and tolerability, impact on pain, disease symptom |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to a total of 2 interim analysis and a final analysis for OS may be performed if PFS is significant for both abemaciclib arms. Health outcome scales are administered day 1 of each cycle. |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of life, pain management and disease symptom control |
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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 | Yes |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Trastuzumab plus physician's choice of standard of care single agent chemotherapy. |
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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
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
Argentina |
Australia |
Belgium |
Brazil |
Canada |
France |
Germany |
Greece |
Italy |
Korea, Republic of |
Mexico |
Spain |
United Kingdom |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |