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Active, Not Recruiting

NCT Number: NCT04546009

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 (persevERA Breast Cancer)

This Phase III, randomized, double-blind, placebo-controlled, multicenter study will evaluate the efficacy and safety of giredestrant combined with palbociclib compared with letrozole combined with palbociclib in patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-negative locally advanced (recurrent or progressed) or metastatic breast cancer.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Centro de Investigaciones Médicas y Desarrollo LC S.R.L, Buenos Aires, Ciudad Autónoma de BuenosAires, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • For women who are premenopausal or perimenopausal and for 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

Exclusion 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

Treatment and study plan

Giredestrant

Drug

Giredestrant is taken orally once per day on Days 1-28 of each 28-day treatment cycle.

Other names: GDC-9545, RO7197597, RG6171

Giredestrant-matched Placebo

Drug

Giredestrant-matched placebo is taken orally once per day on Days 1-28 of each 28-day treatment cycle.

letrozole

Drug

Letrozole 2.5 milligrams (mg) is taken orally once per day on Days 1-28 of each 28-day treatment cycle.

Letrozole-matched Placebo

Drug

Letrozole-matched placebo is taken orally once per day on Days 1-28 of each 28-day treatment cycle.

Palbociclib

Drug

Palbociclib 125 mg is taken orally once per day on Days 1-21 of each 28-day treatment cycle.

LHRH Agonist

Drug

Only premenopausal/perimenopausal and male participants will receive a luteinizing hormone-releasing hormone (LHRH) agonist on Day 1 of each 28-day treatment cycle. The investigator will determine and supply the appropriate LHRH agonist locally approved for use in breast cancer.

Primary outcomes

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

    Time frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 78 months)

Secondary outcomes

  1. Overall Survival

    Time frame: From randomization to death from any cause (up to 78 months)

  2. Objective Response Rate, as Determined by the Investigator According to RECIST v1.1

    Time frame: From randomization until disease progression or death (up to 78 months)

    The objective response rate is defined as the percentage of participants with a complete response or partial response on two consecutive occasions at least (≥)4 weeks apart.

  3. Duration of Response, as Determined by the Investigator According to RECIST v1.1

    Time frame: From first occurrence of documented objective response to disease progression or death from any cause, whichever occurs first (up to 78 months)

  4. Clinical Benefit Rate, as Determined by the Investigator According to RECIST v1.1

    Time frame: From randomization until disease progression or death (up to 78 months)

    The clinical benefit rate is defined as the percentage of participants with stable disease for ≥24 weeks or a complete response or partial response.

  5. Time to Confirmed Deterioration in Pain Level, Defined as the Time to First Documented ≥2-Point Increase from Baseline in the 'Worst Pain' Item from the Brief Pain Inventory-Short Form (BPI-SF) Questionnaire

    Time frame: From Baseline until treatment discontinuation (up to 78 months)

  6. Time to Confirmed Deterioration in Pain Presence and Interference, Defined as the Time to First Documented ≥10-Point Increase from Baseline in the EORTC QLQ-C30 Linearly Transformed Pain Scale Score

    Time frame: From Baseline until treatment discontinuation (up to 78 months)

    EORTC QLQ-C30 = European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire

  7. Time to Confirmed Deterioration in Physical Functioning, Defined as the Time to First Documented ≥10-Point Decrease from Baseline in the EORTC QLQ-C30 Linearly Transformed Physical Functioning Scale Score

    Time frame: From Baseline until treatment discontinuation (up to 78 months)

  8. Time to Confirmed Deterioration in Role Functioning, Defined as the Time to First Documented ≥10-Point Decrease from Baseline in the EORTC QLQ-C30 Linearly Transformed Role Functioning Scale Score

    Time frame: From Baseline until treatment discontinuation (up to 78 months)

  9. Time to Confirmed Deterioration in Global Health Status and Quality of Life (GHS/QoL), Defined as the Time to First Documented ≥10-Point Decrease from Baseline in the EORTC QLQ-C30 Linearly Transformed GHS/QoL Scale Score

    Time frame: From Baseline until treatment discontinuation (up to 78 months)

  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)

    Time frame: From treatment initiation until 30 days after the final dose of study treatment (up to 78 months)

  11. Number of Participants with Vital Sign Abnormalities Over the Course of the Study

    Time frame: Baseline, Days 1 and 15 of Cycles 1 and 2, and Day 1 of each cycle thereafter until treatment discontinuation (1 cycle is 28 days)

    Vital signs include respiratory rate, pulse rate, and systolic and diastolic blood pressure while the participant is in a seated position, and temperature.

  12. Plasma Concentration of Giredestrant at Specified Timepoints

    Time frame: Days 1 and 15 of Cycle 1; Day 1 of Cycles 2, 4, 8, and 16 (1 cycle is 28 days)

  13. Plasma Concentration of Palbociclib at Specified Timepoints

    Time frame: Days 1 and 15 of Cycle 1 (1 cycle is 28 days)

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study title

A Phase III Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of GDC-9545 Combined With Palbociclib Compared With Letrozole Combined With Palbociclib in Patients With Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer

Important dates

Study start
2020
Primary completion
2026
Study completion
2028
First posted
Sep 11, 2020
Registry last updated
May 19, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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