| Protocol No: | ECCT/24/02/09 | Date of Protocol: | 07-07-2023 |
| Study Title: |
This is a Phase III, randomized, open-label multicenter study that will evaluate the efficacy and safety of
giredestrant compared with fulvestrant, both in combination with the investigator's choice of a CDK4/6 inhibitor
(palbociclib, ribociclib or abemaciclib), in participants with estrogen receptor-positive (ER+), human epidermal
growth factor receptor 2-negative (HER2-) advanced breast cancer who have developed resistance to adjuvant
endocrine therapy.
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| Study Objectives: |
Primary Outcome Measures :
Secondary Outcome Measures :
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| Laymans Summary: | A clinical study to compare giredestrant with fulvestrant, both combined with a targeted therapy (CDK4/6 inhibitor) in people with ER-positive, HER2-negative breast cancer that has come back after adjuvant hormone therapy This study is recruiting people with ER-positive, HER2-negative breast cancer that is resistant to a previous adjuvant hormone therapy. People can take part if their cancer has or has not got mutated ERs, and has grown (advanced) or spread to other parts of the body (metastatic). People who take part in this study (participants) will be given the study treatment giredestrant or fulvestrant, both combined with a CDK4/6i (palbociclib, ribociclib or abemaciclib) until their cancer gets worse or they have unacceptable side effects. The study doctor will see them regularly. These hospital visits will include checks to see how the participants respond to the treatment, including any side effects they may have. Total time of participation in the study is expected to be, on average, about 3–5 years, depending on how well treatment works. Participants can stop study treatment and leave the study at any time.
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| Abstract of Study: | Protocol Number: CO44657 Study Name: pionERA Version Number: 1 Test Compound: Giredestrant (RO7197597) The proposed Phase III study is designed to demonstrate a statistically significant and clinically meaningful progressionīfree survival (PFS) benefit of giredestrant compared with fulvestrant, each combined with the investigator's choice of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) between palbociclib, abemaciclib and ribociclib, as first-line (1L) treatment of estrogen receptor-positive (ER+), HER2-negative (HER2-) advanced breast cancer (aBC) resistant to adjuvant endocrine therapy (ET), a patient group considered to have a particularly high unmet need. The proposed enrichment strategy in ESR1 mutation (ESR1m) allows assessment of the co-primary endpoints in the ESR1m subgroup, who have worse prognosis and who are more likely to derive the greatest benefit from novel oral selective estrogen receptor-α antagonists and degraders (SERDs) like giredestrant, and in the full study population, inclusive of participants without an ESR1 mutation detected (ESR1nmd).
Participants in the experimental arm will receive giredestrant 30 mg orally (PO) once a day (QD) on Days 1−28 of each 28-day cycle. Giredestrant will be administered in the clinic on Day 1 of Cycle 1, and on Day 1 of each 28-day cycle thereafter, as indicated in the schedule of activities; it will be taken at home on all non-clinic visit days. Participants in the control arm will receive intramuscular (IM) fulvestrant 500 mg IM on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle. In both arms of the study, all participants will receive the investigator’s choice of CDK4/6i (palbociclib 125 mg or ribociclib 600 mg given PO QD on Days 1−21 of each 28−day cycle, or abemaciclib 150 mg PO twice daily (BID) on Days 1−28 of each 28−day cycle); switching the CDK4/6i for a given patient is not permitted during the study. Modification of the giredestrant dose is not permitted. The dose of abemaciclib, ribociclib, or palbociclib can be reduced up to two times for management of drug-related toxicities. Pre/perimenopausal female and male participants in both arms will also receive a luteinizing hormone-releasing hormone (LHRH) agonist according to local prescribing guidelines. LHRH agonist therapy may be initiated 28 days prior to Day 1 of Cycle 1 (or according to clinical practice for the selected agent) and recommended at least 2 weeks prior to initiation of study treatment. Patients already on one LHRH agonist may remain on the same agent without switching.
Number of patients
Approximately 10 patients (5 on Giredestrant, 5 on Fulvestrant)
End of Study:
A participant is considered to have completed the study if he or she has completed all phases of the study, including the last visit or last scheduled procedure shown in the schedule of activities (see Section 1.3 of the protocol).
The end of this study is defined as the date of the last visit of the last participant in the study/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 potential extended China enrollment phases combined) or the date at which the last data point required for statistical analysis (i.e., see endpoints in Section 3 of the protocol) or safety follow-up is received from the last participant (global and potential extended China enrollment phases combined), whichever occurs later. The end of the study is expected to occur at least 18 months after the last participant is enrolled. In addition, the Sponsor may decide to terminate the study at any time.
Study Duration
The total duration of study participation for each individual is expected to be approximately 40 months (range 1 day to more than 60 months).
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