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A Study of Giredestrant (GDC-9545) in Postmenopausal Women With Stage I-III Operable, Estrogen Receptor-Positive Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03916744
Recruitment Status : Completed
First Posted : April 16, 2019
Last Update Posted : June 18, 2021
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Tracking Information
First Submitted Date  ICMJE April 10, 2019
First Posted Date  ICMJE April 16, 2019
Last Update Posted Date June 18, 2021
Actual Study Start Date  ICMJE July 26, 2019
Actual Primary Completion Date May 25, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 20, 2019)
Change from Baseline in Tumor Cell Proliferation Measured by Ki67 Expression Between Pre- and Post-Treatment Tumor Biopsy Samples [ Time Frame: Baseline and Day 14 or Day 15 ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 12, 2019)
Change from Baseline in Tumor Cell Proliferation Measured by Ki67 Expression Between Pre- and Post-Treatment Tumor Biopsy Samples [ Time Frame: Baseline and Day 15 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 19, 2021)
  • Number of Participants with at Least One Adverse Event and by Severity, Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) [ Time Frame: From Baseline to Day 43 ]
  • Change from Baseline in Pulse Rate [ Time Frame: Baseline, Days 1, 8, 15, and 43 ]
  • Change from Baseline in Systolic Blood Pressure [ Time Frame: Baseline, Days 1, 8, 15, and 43 ]
    Systolic blood pressure will be measured while the participant is in a seated position.
  • Change from Baseline in Diastolic Blood Pressure [ Time Frame: Baseline, Days 1, 8, 15, and 43 ]
    Diastolic blood pressure will be measured while the participant is in a seated position.
  • Change from Baseline in Body Temperature [ Time Frame: Baseline, Days 1, 8, 15, and 43 ]
    Body temperature will be taken by oral or tympanic temperature.
  • Change from Baseline in Prothrombin Time (PT) [ Time Frame: Baseline, Days 1, 8, 15, and 43 ]
  • Change from Baseline in Activated Partial Thromboplastin Time (aPTT) [ Time Frame: Baseline, Days 1, 8, 15, and 43 ]
  • Change from Baseline in International Normalized Ratio (INR) [ Time Frame: Baseline, Days 1, 8, 15, and 43 ]
  • Number of Participants with Laboratory Abnormalities in Hematology Tests by Highest Grade According to NCI-CTCAE v5.0 [ Time Frame: Baseline, Days 1, 8, and 15 ]
    Laboratory parameters for hematology will be measured and compared with a standard reference range. Values outside of the standard reference range are considered abnormalities. Not every laboratory abnormality qualifies as an adverse event. A laboratory test result will be reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment, a medical intervention, or a change in concomitant therapy; or is clinically significant in the investigator's judgment.
  • Number of Participants with Laboratory Abnormalities in Blood Chemistry Tests by Highest Grade According to NCI-CTCAE v5.0 [ Time Frame: Baseline, Days 1, 8, and 15 ]
    Laboratory parameters for blood chemistry will be measured and compared with a standard reference range. Values outside of the standard reference range are considered abnormalities. Not every laboratory abnormality qualifies as an adverse event. A laboratory test result will be reported as an adverse event if it meets any of the following criteria: is accompanied by clinical symptoms; results in a change in study treatment, a medical intervention, or a change in concomitant therapy; or is clinically significant in the investigator's judgment.
  • Plasma Concentration of Giredestrant at Steady State [ Time Frame: Day 15 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 12, 2019)
  • Number of Participants with at Least One Adverse Event and by Severity, Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI-CTCAE v5.0) [ Time Frame: From Baseline to Day 43 ]
  • Change from Baseline in Pulse Rate [ Time Frame: Baseline, Days 1, 8, 15, and 43 ]
  • Change from Baseline in Systolic Blood Pressure [ Time Frame: Baseline, Days 1, 8, 15, and 43 ]
    Systolic blood pressure will be measured while the participant is in a seated position.
  • Change from Baseline in Diastolic Blood Pressure [ Time Frame: Baseline, Days 1, 8, 15, and 43 ]
    Diastolic blood pressure will be measured while the participant is in a seated position.
  • Change from Baseline in Body Temperature [ Time Frame: Baseline, Days 1, 8, 15, and 43 ]
    Body temperature will be taken by oral or tympanic temperature.
  • Change from Baseline in Prothrombin Time (PT) [ Time Frame: Baseline, Days 15 and 43 ]
  • Change from Baseline in Activated Partial Thromboplastin Time (aPTT) [ Time Frame: Baseline, Days 15 and 43 ]
  • Change from Baseline in International Normalized Ratio (INR) [ Time Frame: Baseline, Days 15 and 43 ]
  • Plasma Concentration of GDC-9545 at Steady State [ Time Frame: Day 15 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Giredestrant (GDC-9545) in Postmenopausal Women With Stage I-III Operable, Estrogen Receptor-Positive Breast Cancer
Official Title  ICMJE A Phase I, Multicenter, Open-Label Preoperative, Short-Term Window Study of GDC-9545 in Postmenopausal Women With Stage I-III Operable, Estrogen Receptor-Positive Breast Cancer
Brief Summary This study will evaluate the pharmacodynamics, pharmacokinetics, safety, and biologic activity of giredestrant in participants with Stage I-III operable estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, untreated breast cancer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: Giredestrant
    Giredestrant will be administered orally once daily (QD) starting on Day 1 up to and including the day of surgery (if allowed per local process) on Day 15 (+/-2 days).
    Other Names:
    • GDC-9545
    • RO7197597
    • RG6171
  • Procedure: Surgery
    Breast cancer surgery will take place on Day 15 (+/-2 days).
Study Arms  ICMJE
  • Experimental: Giredestrant Dose Level 1
    Interventions:
    • Drug: Giredestrant
    • Procedure: Surgery
  • Experimental: Giredestrant Dose Level 2
    Interventions:
    • Drug: Giredestrant
    • Procedure: Surgery
  • Experimental: Giredestrant Dose Level 3
    Interventions:
    • Drug: Giredestrant
    • Procedure: Surgery
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 4, 2020)
75
Original Estimated Enrollment  ICMJE
 (submitted: April 12, 2019)
45
Actual Study Completion Date  ICMJE May 25, 2021
Actual Primary Completion Date May 25, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Ability to comply with the study protocol, in the investigator's judgment
  • Histologically confirmed invasive breast carcinoma, with all of the following characteristics: Primary tumor greater than or equal to (≥)1.5 centimeters (cm) in largest diameter by ultrasound; Stage I-III operable breast cancer; Documentation confirming the absence of distant metastasis (M0) as determined by institutional practice.
  • ER-positive tumor and HER2-negative breast cancer as per local laboratory testing
  • Postmenopausal status
  • Breast cancer eligible for primary surgery
  • Submission of a representative tumor tissue specimen
  • Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to (≤)1
  • Adequate organ function

Exclusion Criteria:

  • Diagnosis of inflammatory breast cancer
  • Diagnosis of bilateral breast cancer
  • Concurrent use of hormone replacement therapies
  • Previous systemic or local treatment for the primary breast cancer currently under investigation
  • Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to study entry
  • Current treatment with any systemic anti-cancer therapies
  • Major surgery within 4 weeks prior to enrollment
  • Radiation therapy within 2 weeks prior to enrollment
  • Diagnosis of any secondary malignancy within 3 years prior to enrollment, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer
  • Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or upper gastrointestinal surgery including gastric resection
  • Known HIV infection
  • Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis, current alcohol abuse, or cirrhosis
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
  • History of allergy to giredestrant or any of its excipients
  • Any condition requiring anti-coagulants, such as warfarin, heparin, or thrombolytic drugs
  • History of documented hemorrhagic diathesis or coagulopathy
  • History or presence of symptomatic bradycardia or sick sinus syndrome
  • Baseline heart rate ≤55 beats per minute (bpm) prior to enrollment
  • History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third-degree heart block, or evidence of prior myocardial infarction
  • QT interval corrected through use of Fridericia's formula (QTcF) >470 milliseconds demonstrated by at least two ECGs >30 minutes apart
  • History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease, coronary heart disease, clinically significant electrolyte abnormalities, or family history of sudden unexplained death or long QT syndrome
  • Current treatment with medications that are well known to prolong the QT interval
  • History or presence of uncontrolled hypothyroidism
  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   France,   Spain,   United Kingdom,   United States
Removed Location Countries Germany
 
Administrative Information
NCT Number  ICMJE NCT03916744
Other Study ID Numbers  ICMJE GO40987
2018-003798-85 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
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 Sharing of Clinical Study 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).

Responsible Party Genentech, Inc.
Study Sponsor  ICMJE Genentech, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Genentech, Inc.
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP