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A Study Evaluating the Efficacy and Safety of GDC-9545 Combined With Palbociclib Compared With Letrozole Combined With Palbociclib in Participants With Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT04546009
Recruitment Status : Recruiting
First Posted : September 11, 2020
Last Update Posted : October 26, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This Phase III, randomized, double-blind, placebo-controlled, multicenter study will evaluate the efficacy and safety of GDC-9545 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.

Condition or disease Intervention/treatment Phase
Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer Drug: GDC-9545 Drug: GDC-9545-matched Placebo Drug: Letrozole Drug: Letrozole-matched Placebo Drug: Palbociclib Drug: LHRH Agonist Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 978 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : October 9, 2020
Estimated Primary Completion Date : April 26, 2024
Estimated Study Completion Date : March 18, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: GDC-9545 + Letrozole-matched Placebo + Palbociclib Drug: GDC-9545
GDC-9545 is taken orally once per day on Days 1-28 of each 28-day treatment cycle.
Other Name: RG6171

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

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

Drug: LHRH Agonist
Only premenopausal 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.

Active Comparator: Letrozole + GDC-9545-matched Placebo + Palbociclib Drug: GDC-9545-matched Placebo
GDC-9545-matched placebo is taken orally once per day on Days 1-28 of each 28-day treatment cycle.

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

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

Drug: LHRH Agonist
Only premenopausal 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 Outcome Measures :
  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 Outcome Measures :
  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 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 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 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 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 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 GDC-9545 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) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion 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
  • 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 0-1
  • Adequate organ function

Exclusion Criteria:

  • Disease recurrence during or within 12 months of completing prior neoadjuvant or adjuvant treatment with an aromatase inhibitor (AI)
  • 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)
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04546009


Contacts
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Contact: Reference Study ID Number: BO41843 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global-roche-genentech-trials@gene.com

Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04546009    
Other Study ID Numbers: BO41843
2020-000119-66 ( EudraCT Number )
First Posted: September 11, 2020    Key Record Dates
Last Update Posted: October 26, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).

For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Palbociclib
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Protein Kinase Inhibitors