E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hormone receptor positive, HER2-negative advanced breast cancer |
|
E.1.1.1 | Medical condition in easily understood language |
Advanced breast cancer that is distinguished from other breast cancer types by stage and the presence of molecules that respond to certain hormones |
|
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 | 10072737 |
E.1.2 | Term | Advanced breast cancer |
E.1.2 | System Organ Class | 100000004864 |
|
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 determine whether treatment with alpelisib in combination with fulvestrant prolongs PFS compared to treatment with placebo in combination with fulvestrant for patients with PIK3CA mutant status |
|
E.2.2 | Secondary objectives of the trial |
To determine whether treatment with alpelisib in combination with fulvestrant prolongs overall survival (OS) compared to treatment with placebo in combination with fulvestrant for patients with PIK3CA mutant status
To establish proof of concept of treatment benefit with alpelisib in combination with fulvestrant with respect to PFS for patients with PIK3CA non-mutant status
To evaluate the two treatment arms with respect to OS for patients with PIK3CA non-mutant status
To evaluate the two treatment arms and cohorts of interest with respect to overall response rate (ORR) and clinical benefit rate
Further secondary objectives and details are described in the protocol |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient is an adult ≥ 18 years old at the time of informed consent
2. Patient has adequate FFPE tumor tissue for the analysis of PIK3CA mutational status
3. Patient has identified PIK3CA status
4. If female, then the patient is postmenopausal
5. Patient has radiological or objective evidence of recurrence or progression
6. Patient has a histologically and/or cytologically confirmed diagnosis of ER+ and/or PgR+ breast cancer
7. Patient has HER2-negative breast cancer
8. Patient has either measurable disease (at least one measurable lesion as per RECIST 1.1) or at least one predominantly lytic bone lesion
9. Patient has advanced (loco regionally recurrent not amenable to curative therapy or metastatic) breast cancer
10. Patient has recurrence or progression of disease during or after AI therapy (i.e. letrozole, anastrozole, exemestane)
Further inclusion criteria and details are described in the protocol |
|
E.4 | Principal exclusion criteria |
1. Patient with symptomatic visceral disease or any prohibitive disease burden
2. Patient has received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, any PI3K, mTOR or AKT inhibitor
3. Patient has a known hypersensitivity to any of the excipients of alpelisib or fulvestrant
4. Patient with inflammatory breast cancer at screening
5. Patient is concurrently using other anti-cancer therapy
6. Patient has had surgery within 14 days prior to starting study drug or has not recovered from major side effects
7. Patient has not recovered from all toxicities related to prior anticancer therapies except alopecia
Further exclusion criteria and details are described in the protocol |
|
E.5 End points |
E.5.1 | Primary end point(s) |
PFS based on local radiology assessments and using RECIST 1.1 criteria in the PIK3CA mutant cohort |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At screening/baseline, every 8 weeks after randomization during the first 18 months and every 12 weeks until 36 months, then change to as
clinically indicated |
|
E.5.2 | Secondary end point(s) |
PFS based on local radiology assessments and using RECIST 1.1 criteria in the PIK3CA non-mutant cohort
OS in each of the PIK3CA mutant and non-mutant cohorts
ORR and CBR in each of the PIK3CA mutant and non-mutant cohorts
Further secondary endpoints are described in the protocol |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At screening/baseline, every 8 weeks after randomization during the first 18 months and every 12 weeks until 36 months, then change to as
clinically indicated |
|
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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 120 |
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 |
Austria |
Belgium |
Brazil |
Bulgaria |
Canada |
Chile |
Colombia |
Czech Republic |
Denmark |
France |
Germany |
Hong Kong |
India |
Israel |
Italy |
Japan |
Korea, Republic of |
Lebanon |
Mexico |
Netherlands |
Norway |
Peru |
Portugal |
Russian Federation |
Singapore |
Spain |
Sweden |
Taiwan |
Thailand |
Turkey |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
The end of the overall study is defined as the time point when data collection will stop in both cohorts and the final analysis of the study will occur. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |