E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Estrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer |
|
E.1.1.1 | Medical condition in easily understood language |
Breast cancer begins when abnormal cancerous cells in the breast grow and multiply to create a tumor. This tumor can be ER-positive, HER2-negative |
|
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 | 23.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10070575 |
E.1.2 | Term | Estrogen receptor positive breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10070577 |
E.1.2 | Term | Oestrogen receptor positive breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10083232 |
E.1.2 | Term | HER2 negative breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
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 the efficacy of GDC-9545 combined with palbociclib compared with letrozole combined with palbociclib on the basis of progression-free survival |
|
E.2.2 | Secondary objectives of the trial |
-To evaluate the efficacy of GDC-9545 combined with palbociclib compared with letrozole combined with palbociclib on the basis of overall survival, objective response rate, duration of response, clinical benefit rate, time to deterioration, time to deterioration in pain presence and interference, time to deterioration in physical functioning, time to deterioration in role functioning, time to deterioration in global health status -To evaluate the safety of GDC-9545 combined with palbociclib compared with letrozole combined with palbociclib -To characterize the GDC-9545 pharmacokinetics profile when given in combination with palbociclib -To characterize the palbociclib pharmacokinetics profile when given in combination with GDC-9545 or in combination with letrozole
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
–Age >= 18 years at time of signing Informed Consent Form –For women who are premenopausal or perimenopausal or men: treatment with approved LHRH agonist therapy for the duration of study treatment –Locally advanced (recurrent or progressed) or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent –Documented ER-positive tumor and HER2-negative tumor, assessed locally –No history of systemic anti-cancer therapy for locally advanced (recurrent or progressed) or metastatic disease –Measurable disease as defined per RECIST v.1.1 –Eastern Cooperative Oncology Group Performance Status 01 –Adequate organ function
|
|
E.4 | Principal exclusion criteria |
–Disease recurrence during or within 12 months of completing prior neoadjuvant or adjuvant treatment with an AI –Disease recurrence during or within 12 months of completing prior neoadjuvant or adjuvant treatment with any CDK4/6 inhibitor –Prior treatment with a SERD –Prior treatment with tamoxifen is permitted, provided the patient did not experience disease recurrence within the first 24 months of treatment with tamoxifen –Treatment with any investigational therapy within 28 days prior to study treatment –Advanced, symptomatic, visceral spread that is at risk of life-threatening complications –Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease –Active cardiac disease or history of cardiac dysfunction –Pregnant or breastfeeding
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
1. Progression-free survival as determined by the investigator |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Approximately 82 months |
|
E.5.2 | Secondary end point(s) |
Efficacy 1. Overall survival 2. Objective response rate as determined by the investigator 3. Duration of response as determined by the investigator 4. Clinical benefit rate as determined by the investigator 5. Time to deterioration in pain level 6. Time to deterioration in pain presence and interference, in physical functioning, in role functioning, and in global health status 7. Incidence and severity of adverse events, with severity determined according to NCI CTCAE v5.0 8. Change from baseline in targeted vital signs 9. Plasma concentration of GDC-9545 at specified timepoints 10. Plasma concentration of palbociclib at specified timepoints
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-7. Approximately 82 months 8. From baseline (Day-28 to -1) to 82 months 9. Day 1 and 15 of Cycle 1, Day 1 of Cycle 2, 4, 8, and 16 and at treatment discontinuation 10. Day 1 and 15 of Cycle 1
|
|
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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
|
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 | 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) | Yes |
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 118 |
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 |
China |
Denmark |
France |
Germany |
Greece |
Hong Kong |
Hungary |
Italy |
Korea, Republic of |
Mexico |
New Zealand |
Peru |
Poland |
Portugal |
South Africa |
Spain |
Switzerland |
Turkey |
Ukraine |
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 this study (global phase and China extension phase) is defined as the date when the last patient, last visit occurs or the date at which the last data point required for statistical analysis or overall survival follow-up is received from the last patient, whichever occurs later. The end of the study is expected to occur at least 60 months after the last patient is enrolled. In addition, the Sponsor may decide to terminate the study at any time. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 74 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 82 |