| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Estrogen Receptor-Positive, HER2-Negative Early Breast Cancer. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Breast cancer is a disease in which cells in the breast grow out of control. |
|
| 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 | 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 demonstrate superiority of giredestrant over the control treatment |
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of giredestrant compared with Endocrine
Therapy of Physician's Choice (TPC)
• To evaluate the safety of giredestrant compared with TPC
• To characterize giredestrant pharmacokinetics (PK)
• To evaluate health status utility scores of participants treated with
giredestrant compared with TPC |
|
| 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 |
SUBSTUDY TITLE: AN OPEN-LABEL, SINGLE ARM SUBSTUDY TO EXPLORE
THE SAFETY AND EFFICACY OF GIREDESTRANT IN COMBINATION WITH
ABEMACICLIB IN PATIENTS WITH ESTROGEN RECEPTOR.POSITIVE,
HER2-NEGATIVE EARLY BREAST CANCER
PROTOCOL NUMBER: GO42784 Substudy 1 giredestrant + abemaciclib
VERSION NUMBER: 1
DATE: 25AUG23
PRIMARY OBJECTIVE: To evaluate the safety of giredestrant in
combination with abemaciclib |
|
| E.3 | Principal inclusion criteria |
- Participants who received adjuvant chemotherapy or no chemotherapy
must have the following:
– No pathological involved nodes (pN0) and primary tumor larger than
1 cm, and must fulfill at least one of the features: Grade 3 or Ki67≥20%
or Oncotype DX ≥26 (if available) or High-Risk MammaPrint (if
available)
or
– Pathological node-positive disease (microscopic and/or macroscopic
tumor involvement, ≥pN1) and will be stratified in medium or high risk
based on additional biological criteria: Grade, Ki67, Oncotype DX or
MammaPrint
-Participants who received neoadjuvant chemotherapy must have
residual disease in lymph nodes (≥ypN1) after neoadjuvant
chemotherapy.
- Participants with any pT primary tumor and pN2 or any pT primary
tumor and pN3 or pT4 primary tumor and any pN.
- Participants who have documented ER+ (positive) tumor by
immunohistochemistry, as assessed locally on a primary disease
specimen and defined as ≥ 1% of tumor cells stained positive according
to the ASCO/College of American Pathologists (CAP) guidelines or
European Society of Medical Oncology (ESMO) guidelines or any national
guidelines with criteria conforming to ASCO/CAP or ESMO guidelines.
- Participants must have undergone definitive surgery of their primary
breast tumor(s) and axillary lymph nodes (ALND and/or SLNB).
- Participants who received adjuvant chemotherapy must have
completed adjuvant chemotherapy prior to randomization. Participants
may also have received neoadjuvant chemotherapy. A washout period of
at least 21 days is required between last adjuvant chemotherapy dose
and randomization. |
|
| E.4 | Principal exclusion criteria |
- Participants who have been diagnosed with Stage IV breast cancer
- Participants who are pregnant or breastfeeding, or intending to become
pregnant during the study or within 10 days after the final dose of
giredestrant, or within the time period specified per local prescribing
guidelines after the final dose of TPC.
- Participants who have received treatment with investigational therapy
within 28 days prior to initiation of study treatment or are currently
enrolled in any other type of medical research that is scientifically or
medically incompatible with this study
- Participants receiving or planning to receive a CDK4/6i as
(neo)adjuvant therapy. Short course of up to 12 weeks of neoadjuvant
or adjuvant treatment with CDK4/6 inhibitor therapy prior to
randomization is allowed.
- Participants who have active cardiac disease or history of cardiac
dysfunction
- Participants who have a history of any prior (ipsilateral and/or
contralateral) invasive breast cancer or ductal carcinoma in situ (DCIS).
Participants with a history of contralateral DCIS treated by only local
regional therapy at any time may be eligible.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| 1. Invasive disease-free survival (IDFS), defined as the time from randomization to first occurrence of one of the following IDFS events; ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, and death from any cause |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 1. Up to approximately 10 years |
|
| E.5.2 | Secondary end point(s) |
1. Overall survival, defined as the time from randomization to death from any cause
2. IDFS (per STEEP), including second primary non-breast cancer, defined in the same way as the primary IDFS, but including second primary non-breast invasive cancer as an event (with the exception of non-melanoma skin cancers and in situ carcinomas of any site)
3. Disease-free survival (DFS), defined as the time from randomization to first occurrence of an IDFS (per STEEP) event, including second primary non-breast cancer event or contralateral or ipsilateral DCIS
4. Distant recurrence-free interval (DRFI), defined as the time from randomization to first occurrence of a DRFI event
5. Locoregional recurrence-free interval (LRRFI), defined as the time from randomization to first occurrence of an LRRFI event
6. Mean and mean change from baseline in physical functioning, role functioning, and global health status/ quality of life (QoL) at relevant timepoints as assessed through use of the European Organisation for the Research and Treatment of Cancer Quality-of-Life Questionnaire - Core 30 (EORTC QLQ-C30) respective scale scores
7. Incidence and severity of adverse events, with severity determined according to NCI CTCAE 5.0
8. Change from baseline in targeted vital signs and clinical laboratory test results
9. Plasma concentrations of giredestrant at specified timepoints
10. Change from baseline in EuroQol 5-Dimension Questionnaire, 5-level version (EQ 5D-5L) index-based and visual analogue scale scores at relevant timepoint
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| 1-10. Up to approximately 10 years |
|
| 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 |
| health status of participants. |
|
| 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 | 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) | Yes |
| E.8.2.2 | Placebo | No |
| 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 | 250 |
| 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 |
| Chile |
| Colombia |
| Costa Rica |
| Egypt |
| Guatemala |
| Malaysia |
| Peru |
| Philippines |
| Uganda |
| Switzerland |
| Bosnia and Herzegovina |
| North Macedonia |
| Ukraine |
| Hong Kong |
| Taiwan |
| Australia |
| Belarus |
| Brazil |
| Canada |
| China |
| Georgia |
| India |
| Israel |
| Japan |
| Kenya |
| Korea, Republic of |
| Mexico |
| Russian Federation |
| Serbia |
| South Africa |
| Thailand |
| United Kingdom |
| United States |
| Viet Nam |
| Austria |
| Belgium |
| Bulgaria |
| Croatia |
| Czechia |
| Finland |
| France |
| Germany |
| Greece |
| Hungary |
| Ireland |
| Italy |
| Latvia |
| Netherlands |
| Poland |
| Portugal |
| Slovakia |
| Slovenia |
| Spain |
| Sweden |
| Türkiye |
|
| 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 is defined as the date of the last scheduled procedure shown in the schedule of activities for the last participant in the study globally (i.e.: last participant in the global and extended China enrollment phases combined), or the date at which the last data point required for statistical analysis or safety follow-up is received from the last participant (global and extended China enrollment phases combined), whichever occurs later. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 10 |
| 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 | 10 |
| 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 |
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