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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03916744




Registration number
NCT03916744
Ethics application status
Date submitted
10/04/2019
Date registered
16/04/2019
Date last updated
8/08/2019

Titles & IDs
Public title
A Study of GDC-9545 in Postmenopausal Women With Stage I-III Operable, Estrogen Receptor-Positive Breast Cancer
Scientific title
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
Secondary ID [1] 0 0
2018-003798-85
Secondary ID [2] 0 0
GO40987
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GDC-9545
Treatment: Surgery - Surgery

Experimental: GDC-9545 Dose Level 1 -

Experimental: GDC-9545 Dose Level 2 -

Experimental: GDC-9545 Dose Level 3 -


Treatment: Drugs: GDC-9545
GDC-9545 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).

Treatment: Surgery: Surgery
Breast cancer surgery will take place on Day 15 (+/-2 days).

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Surgery
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from Baseline in Tumor Cell Proliferation Measured by Ki67 Expression Between Pre- and Post-Treatment Tumor Biopsy Samples
Timepoint [1] 0 0
Baseline and Day 15
Secondary outcome [1] 0 0
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)
Timepoint [1] 0 0
From Baseline to Day 43
Secondary outcome [2] 0 0
Change from Baseline in Pulse Rate
Timepoint [2] 0 0
Baseline, Days 1, 8, 15, and 43
Secondary outcome [3] 0 0
Change from Baseline in Systolic Blood Pressure - Systolic blood pressure will be measured while the participant is in a seated position.
Timepoint [3] 0 0
Baseline, Days 1, 8, 15, and 43
Secondary outcome [4] 0 0
Change from Baseline in Diastolic Blood Pressure - Diastolic blood pressure will be measured while the participant is in a seated position.
Timepoint [4] 0 0
Baseline, Days 1, 8, 15, and 43
Secondary outcome [5] 0 0
Change from Baseline in Body Temperature - Body temperature will be taken by oral or tympanic temperature.
Timepoint [5] 0 0
Baseline, Days 1, 8, 15, and 43
Secondary outcome [6] 0 0
Change from Baseline in Prothrombin Time (PT)
Timepoint [6] 0 0
Baseline, Days 15 and 43
Secondary outcome [7] 0 0
Change from Baseline in Activated Partial Thromboplastin Time (aPTT)
Timepoint [7] 0 0
Baseline, Days 15 and 43
Secondary outcome [8] 0 0
Change from Baseline in International Normalized Ratio (INR)
Timepoint [8] 0 0
Baseline, Days 15 and 43
Secondary outcome [9] 0 0
Plasma Concentration of GDC-9545 at Steady State
Timepoint [9] 0 0
Day 15

Eligibility
Key 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

- Confirmed diagnosis of breast cancer

- Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to
(=)1

- Adequate organ function
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Diagnosis of inflammatory 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

- Pregnant, lactating, or breastfeeding

- 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 and 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

Study design
Purpose of the study
Basic Science
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
St Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [2] 0 0
Peter MacCallum Cancer Centre-Box Hill - East Melbourne
Recruitment hospital [3] 0 0
Sunshine Hospital - St Albans
Recruitment hospital [4] 0 0
Fiona Stanley Hospital; Investigational Drugs, Pharmacy Department - Murdoch
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3002 - East Melbourne
Recruitment postcode(s) [3] 0 0
3021 - St Albans
Recruitment postcode(s) [4] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Colorado
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
Belgium
State/province [4] 0 0
Auderghem
Country [5] 0 0
Belgium
State/province [5] 0 0
Hasselt
Country [6] 0 0
Belgium
State/province [6] 0 0
Namur
Country [7] 0 0
Belgium
State/province [7] 0 0
Wilrijk
Country [8] 0 0
France
State/province [8] 0 0
Lille
Country [9] 0 0
France
State/province [9] 0 0
Rennes
Country [10] 0 0
France
State/province [10] 0 0
Saint Herblain
Country [11] 0 0
France
State/province [11] 0 0
Saint-Cloud
Country [12] 0 0
France
State/province [12] 0 0
Toulouse
Country [13] 0 0
Germany
State/province [13] 0 0
Dresden
Country [14] 0 0
Germany
State/province [14] 0 0
Hannover
Country [15] 0 0
Germany
State/province [15] 0 0
Homburg/Saar
Country [16] 0 0
Germany
State/province [16] 0 0
Munchen
Country [17] 0 0
Spain
State/province [17] 0 0
Barcelona
Country [18] 0 0
Spain
State/province [18] 0 0
Guipuzcoa
Country [19] 0 0
Spain
State/province [19] 0 0
Madrid
Country [20] 0 0
Spain
State/province [20] 0 0
Valencia
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Liverpool
Country [22] 0 0
United Kingdom
State/province [22] 0 0
London
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Truro

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Genentech, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will evaluate the pharmacodynamics, pharmacokinetics, safety, and biologic
activity of GDC-9545 in participants with Stage I-III operable estrogen receptor
(ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, untreated breast
cancer.
Trial website
https://clinicaltrials.gov/show/NCT03916744
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: GO40987 www.roche.com/about_roche/roche_worldwide.htm
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. Only)
Fax 0 0
Email 0 0
global-roche-genentech-trials@gene.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03916744