A Study Evaluating the Efficacy and Safety of Giredestrant Combined With Palbociclib Compared With Letrozole Combined With Palbociclib in Participants With Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer

JRCT ID: jRCT2071200038

Registered date:08/10/2020

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: PATIENTS WITH ESTROGEN RECEPTOR-POSITIVE, HER2-NEGATIVE LOCALLY ADVANCED OR METASTATIC BREAST CANCE
• Date of first enrollment: 09/10/2020
• Target sample size: 992
• Countries of recruitment: Argentina,Japan,Australia,Japan,Austria,Japan,Belgium,Japan,Brazil,Japan,Canada,Japan,Denmark,Japan,France,Japan,Germany,Japan,Greece,Japan,Hong Kong,Japan,Hungary,Japan,Israel,Japan,Italy,Japan,Korea,Japan,New Zealand,Japan,Poland,Japan,Portugal,Japan,Russian Federation,Japan,Spain,Japan,Taiwan,Japan,Thailand,Japan,Turkey,Japan,Ukraine,Japan,United Kingdom,Japan,United States,Japan,China,Japan,Mexico,Japan,Peru,Japan
• Study type: Interventional

Intervention(s)

GDC-9545: taken orally once per day on Days 1-28 of each 28-day treatment cycle.
palbociclib: 125 mg is taken orally once per day on Days 1-21 of each 28-day treatment cycle.
letrozole: 2.5 mg is taken orally once per day on Days 1-28 of each 28-day treatment cycle.

A luteinizing hormone-releasing hormone (LHRH) agonist will be administered to male participants and premenopausal/perimenopausal participants according to local prescribing information. The investigator may determine and supply the appropriate LHRH agonist locally approved for use in breast cancer.

Outcome(s)

Primary Outcome

Efficacy
Progression-Free Survival (PFS), as Determined by the Investigator According to RECIST v1.1

Secondary Outcome

Efficacy
1.Overall Survival
2.Objective Response Rate, as Determined by the Investigator According to RECIST v1.1
3.Duration of Response, as Determined by the Investigator According to RECIST v1.1
4.Clinical Benefit Rate, as Determined by the Investigator According to RECIST v1.1
5.Time to Confirmed Deterioration in Pain Level, the Brief Pain Inventory-Short Form (BPI-SF) Questionnaire
6.Time to Confirmed Deterioration in Pain Presence and Interference, EORTC QLQ-C30
7.Time to Confirmed Deterioration in Physical Functioning, EORTC QLQ-C30
8.Time to Confirmed Deterioration in Role Functioning, EORTC QLQ-C30
9.Time to Confirmed Deterioration in Global Health Status and Quality of Life (GHS/QoL), EORTC QLQ-C30

Safety, Pharmacokinetics
10.Number of Participants with Adverse Events, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0)
11.Number of Participants with Vital Sign Abnormalities Over the Course of the Study
12.Plasma Concentration of Giredestrant at Specified Timepoints
13.Plasma Concentration of Palbociclib at Specified Timepoints

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

-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
-Patients who have bilateral breast cancers which are both ER-positive and HER2-negative can be included in the study because the metastases are suitably targeted by the study treatments. If patients have bilateral tumors which are of different biomarker status, then proof of the ER and HER2 status of the metastases is required for study entry
-No history of systemic anti-cancer therapy for locally advanced (recurrent or progressed) or metastatic disease
-Disease recurrence from early-stage breast cancer after standard adjuvant endocrine therapy meeting the protocol-defined criteria of having received at least 24 months of treatment without disease progression during treatment and a disease-free interval since the completion of treatment that was greater than 12 months
-Measurable disease as defined per RECIST v.1.1 or bone only disease which must have at least one predominantly lytic bone lesion confirmed by CT or MRI which can be followed
-Eastern Cooperative Oncology Group Performance Status 0-1
-Adequate organ function

Exclude criteria

-Disease recurrence during or within 12 months of completing prior neoadjuvant or adjuvant treatment with any CDK4/6 inhibitor
-Prior treatment with a selective estrogen receptor degrader (SERD)
-Treatment with any investigational therapy within 28 days prior to study treatment
-Treatment with strong CYP3A inhibitors or inducers within 14 days or 5 drug elimination half-lives (whichever is longer) prior to randomization
-Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term
-Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
-Active cardiac disease or history of cardiac dysfunction, as defined in the protocol
-Pregnant or breastfeeding

Related Information

• Primary Sponsor: Clinical trials information
• Secondary ID(s): NCT04546009