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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03332797




Registration number
NCT03332797
Ethics application status
Date submitted
1/11/2017
Date registered
6/11/2017
Date last updated
21/09/2020

Titles & IDs
Public title
A Study of GDC-9545 Alone or in Combination With Palbociclib and/or Luteinizing Hormone-Releasing Hormone (LHRH) Agonist in Locally Advanced or Metastatic Estrogen Receptor-Positive Breast Cancer
Scientific title
A Phase Ia/Ib, Multicenter, Open-Label, Dose Escalation, Dose Expansion Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-9545 Alone or in Combination With Palbociclib and/or LHRH Agonist in Patients With Locally Advanced or Metastatic Estrogen Receptor-Positive Breast Cancer
Secondary ID [1] 0 0
2017-002083-41
Secondary ID [2] 0 0
GO39932
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: Drugs - Palbociclib
Treatment: Drugs - LHRH Agonist

Experimental: Dose Escalation: GDC-9545 - During dose escalation, postmenopausal participants will be assigned sequentially to escalating doses of GDC-9545, up to the maximum tolerated dose (MTD) or maximum administered dose (MAD).

Experimental: Dose Escalation: Cohort B0: GDC-9545 + Palbociclib - GDC-9545 will be administered to postmenopausal participants, at a dose lower than the MTD or MAD determined in single-agent dose escalation, in combination with the label-recommended dose of palbociclib.

Experimental: Dose Expansion: Cohort A1: GDC-9545 Dose 1 - GDC-9545 will be administered to postmenopausal participants as a single-agent at a dose that is less than or equal to the MTD/MAD (Dose 1).

Experimental: Dose Expansion: Cohort A2: GDC-9545 Dose 1 + LHRH - GDC-9545 will be administered to pre- or perimenopausal participants at a dose that is less than or equal to the MTD/MAD (Dose 1) in combination with an approved LHRH agonist.

Experimental: Dose Expansion: Cohort A3: GDC-9545 Dose 2 - GDC-9545 will be administered to postmenopausal participants as a single-agent at a dose that is less than or equal to the MTD/MAD (Dose 2).

Experimental: Dose Expansion: Cohort A4: GDC-9545 Dose 2 + LHRH - GDC-9545 will be administered to pre- or perimenopausal participants at a dose that is less than or equal to the MTD/MAD (Dose 2) in combination with an LHRH agonist.

Experimental: Dose Expansion: Cohort A5: GDC-9545 Dose 3 - GDC-9545 will be administered to postmenopausal participants as a single-agent at a dose that is less than or equal to the MTD/MAD (Dose 3).

Experimental: Dose Expansion: Cohort B1: GDC-9545 + Palbociclib - GDC-9545 will be administered to postmenopausal participants, at a dose that is less than or equal to the MTD/MAD, in combination with the label-recommended dose of palbociclib.

Experimental: Dose Expansion: Cohort B2: GDC-9545 + Palbociclib + LHRH - GDC-9545 will be administered to pre- or perimenopausal participants, at a dose that is less than or equal to the MTD/MAD, in combination with the label-recommended dose of palbociclib and an approved LHRH agonist.

Experimental: Dose Expansion: Cohort C1: GDC-9545 Dose 2 +/- Palbociclib - GDC-9545 will be administered to postmenopausal participants at a pre-defined dose level (Dose 2) as a single agent for 14 days, followed by treatment with either GDC-9545 (Dose 2) plus palbociclib or GDC-9545 (Dose 2) alone for the duration of the study, as determined by the investigator.

Experimental: Dose Expansion: Cohort C2: GDC-9545 Dose 2 + Palbociclib - GDC-9545 will be administered to postmenopausal participants at a pre-defined dose level (Dose 2), in combination with the label-recommended dose of palbociclib.

Experimental: Dose Expansion: Cohort X: GDC-9545 Dose 3 - GDC-9545 will be administered at a pre-defined dose level (Dose 3) to postmenopausal participants currently receiving clinical benefit with GDC-0927 or GDC-0810 on Studies GO29656 (NCT02316509) or GO29642 (NCT01823835), respectively, upon completion of their studies.


Treatment: Drugs: GDC-9545
GDC-9545 will be administered orally, once daily, on Days 1-28 of each 28-day cycle, until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.

Treatment: Drugs: Palbociclib
Palbociclib will be administered orally, once daily, at the label-recommended dose of 125 mg on Days 1-21 of each 28-day cycle, until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.

Treatment: Drugs: LHRH Agonist
The LHRH agonist will be administered by injection once every 4 weeks on Day 1 of each 28-day cycle, according to the label. The investigator will choose the appropriate LHRH agonist approved for use in breast cancer.

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

Outcomes
Primary outcome [1] 0 0
Number of Participants with Adverse Events by Severity, According to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE v4.0)
Timepoint [1] 0 0
From Baseline until 28 days after the last dose of study treatment (up to 48 months)
Primary outcome [2] 0 0
Dose Escalation: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of GDC-9545 When Administered as a Single Agent or in Combination with Palbociclib
Timepoint [2] 0 0
Days -7 to 28 of Cycle 1
Primary outcome [3] 0 0
Dose Escalation: Number of Participants with Dose-Limiting Toxicities When GDC-9545 is Administered as a Single Agent or in Combination with Palbociclib
Timepoint [3] 0 0
Days -7 to 28 of Cycle 1
Primary outcome [4] 0 0
Change from Baseline in Systolic Blood Pressure Over Time
Timepoint [4] 0 0
Baseline and at each treatment cycle (1 cycle is 28 days) through to 28 days after the last dose of study treatment
Primary outcome [5] 0 0
Change from Baseline in Diastolic Blood Pressure Over Time
Timepoint [5] 0 0
Baseline and at each treatment cycle (1 cycle is 28 days) through to 28 days after the last dose of study treatment
Primary outcome [6] 0 0
Change from Baseline in Body Temperature Over Time
Timepoint [6] 0 0
Baseline and at each treatment cycle (1 cycle is 28 days) through to 28 days after the last dose of study treatment
Primary outcome [7] 0 0
Change from Baseline in Pulse Rate Over Time
Timepoint [7] 0 0
Baseline and at each treatment cycle (1 cycle is 28 days) through to 28 days after the last dose of study treatment
Primary outcome [8] 0 0
Change from Baseline in Respiration Rate Over Time
Timepoint [8] 0 0
Baseline and at each treatment cycle (1 cycle is 28 days) through to 28 days after the last dose of study treatment
Primary outcome [9] 0 0
Change from Baseline in Electrocardiogram (ECG) Results Over Time: Heart Rate
Timepoint [9] 0 0
Baseline and at predefined intervals from Cycle 1 and at each subsequent cycle (1 cycle is 28 days) through to the last dose of study treatment
Primary outcome [10] 0 0
Change from Baseline in ECG Results Over Time: PR Duration
Timepoint [10] 0 0
Baseline and at predefined intervals from Cycle 1 and at each subsequent cycle (1 cycle is 28 days) through to the last dose of study treatment
Primary outcome [11] 0 0
Change from Baseline in ECG Results Over Time: QRS Duration
Timepoint [11] 0 0
Baseline and at predefined intervals from Cycle 1 and at each subsequent cycle (1 cycle is 28 days) through to the last dose of study treatment
Primary outcome [12] 0 0
Change from Baseline in ECG Results Over Time: QT Duration
Timepoint [12] 0 0
Baseline and at predefined intervals from Cycle 1 and at each subsequent cycle (1 cycle is 28 days) through to the last dose of study treatment
Primary outcome [13] 0 0
Change from Baseline in ECG Results Over Time: QTcF Duration
Timepoint [13] 0 0
Baseline and at predefined intervals from Cycle 1 and at each subsequent cycle (1 cycle is 28 days) through to the last dose of study treatment
Primary outcome [14] 0 0
Change from Baseline in ECG Results Over Time: RR Duration
Timepoint [14] 0 0
Baseline and at predefined intervals from Cycle 1 and at each subsequent cycle (1 cycle is 28 days) through to the last dose of study treatment
Primary outcome [15] 0 0
Number of Participants with Clinical Laboratory Abnormalities in Hematology Tests by Highest Grade According to NCI-CTCAE v4.0 - 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.
Timepoint [15] 0 0
Baseline, Cycle 1, and at each subsequent cycle (1 cycle is 28 days) or at every other cycle starting from Cycle 3 (Cohort X only), up to 28 days after the last dose of study treatment
Primary outcome [16] 0 0
Number of Participants with Clinical Laboratory Abnormalities in Blood Chemistry Tests by Highest Grade According to NCI-CTCAE v4.0 - 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.
Timepoint [16] 0 0
Baseline, Cycle 1, and at each subsequent cycle (1 cycle is 28 days) or at every other cycle starting from Cycle 3 (Cohort X only), up to 28 days after the last dose of study treatment
Primary outcome [17] 0 0
Number of Participants with Clinical Laboratory Abnormalities in Urinalysis Tests by Highest Grade According to NCI-CTCAE v4.0 - Laboratory parameters for urinalysis 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.
Timepoint [17] 0 0
Baseline, Cycle 3, and at every other cycle (1 cycle is 28 days) up to 28 days after the last dose of study treatment
Secondary outcome [1] 0 0
Plasma Concentration of GDC-9545 Over Time
Timepoint [1] 0 0
At predefined intervals from Cycle 1, Day -7 (Single-Agent Dose Escalation and A1-A5 only) or Cycle 1, Day 1 (B0, B1, and B2) to Cycle 4, Day 1 (1 cycle is 28 days) and at study completion; Cycle 1, Days -7 or 8 (C1 only); Cycle 1, Day 8 (C2 only)
Secondary outcome [2] 0 0
Plasma Concentration of Palbociclib Over Time
Timepoint [2] 0 0
At predefined intervals from Cycle 1, Day 1 to Cycle 4, Day 1 (1 cycle is 28 days) and at study completion (B0, B1, and B2 only); Cycle 1, Day 8 (C2 only)
Secondary outcome [3] 0 0
Plasma Concentration of LHRH Over Time
Timepoint [3] 0 0
At predefined intervals from Cycle 1, Day 1 to Cycle 4, Day 1 (1 cycle is 28 days) and at study completion (B2 only)
Secondary outcome [4] 0 0
Percentage of Participants with Objective Response - Objective response is defined as a complete response or partial response on two consecutive occasions =4 weeks apart, as determined by the investigator according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1).
Timepoint [4] 0 0
For all cohorts, except for Cohort X: Baseline and every 8 weeks from Cycle 1, Day 1 until end of study treatment (up to 48 months)
Secondary outcome [5] 0 0
Clinical Benefit Rate - Clinical benefit rate is defined as the percentage of participants achieving either of the following: confirmed complete response or partial response (as determined by the investigator according to RECIST v1.1); or the first occurrence of progressive disease after 24 weeks of study treatment.
Timepoint [5] 0 0
For all cohorts, except for Cohort X: Baseline and every 8 weeks from Cycle 1, Day 1 until end of study treatment (up to 48 months)
Secondary outcome [6] 0 0
Duration of Response
Timepoint [6] 0 0
For all cohorts, except for Cohort X: From the first occurrence of a documented objective response until first observation of disease progression or death from any cause on study, whichever occurs first (up to 48 months)

Eligibility
Key inclusion criteria
Inclusion Criteria for Dose Escalation:

- Histologically or cytologically proven diagnosis of adenocarcinoma of the breast with
evidence of either locally recurrent disease not amenable to resection or radiation
therapy with curative intent or with metastatic disease

- Estrogen receptor (ER)-positive tumor

- Human epidermal growth factor receptor 2 (HER2)-negative breast cancer as per local
laboratory testing

- Measurable disease, or evaluable bone disease; that is, bone lesions that are lytic or
mixed (lytic + sclerotic) in the absence of measurable lesion

- Required paired pre- and on-treatment tumor biopsies for participants with metastases
that are safely accessible as determined by the investigator

- Advanced or metastatic ER-positive/HER2-negative breast cancer that has recurred or
progressed while being treated with adjuvant endocrine therapy for a duration of at
least 24 months and/or endocrine therapy in the incurable, locally advanced, or
metastatic setting and derived a clinical benefit from therapy (i.e., tumor response
or stable disease for at least 6 months)

- No more than 2 prior lines of treatment for advanced or metastatic breast cancer

- Greater than or equal to (=)2 weeks must have elapsed from the use of any other
endocrine, targeted therapy or chemotherapy

- Single-Agent Cohorts (only applies to Dose Escalation): Advanced or metastatic disease
that is either refractory to or intolerant of existing standard therapy or for which
no effective standard therapy that confers clinical benefit is available

- Cohort B0: No prior treatment with cyclin-dependent kinase 4/6 (CDK4/6) inhibitor

- For participants undergoing 18F-fluoroestradiol-positron emission tomography (FES-PET)
imaging additional restrictions on prior therapy include: =2 months must have elapsed
from the use of tamoxifen; =6 months must have elapsed from the use of fulvestrant

- Postmenopausal status

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

- Resolution of all acute toxic effects of prior therapy or surgical procedures to
baseline or Grade =1 (except alopecia or other toxicities not considered to be a
safety risk for the patient)

- Life expectancy of =12 weeks

- Adequate organ function

Inclusion Criteria for Dose Expansion:

Same criteria as above for Dose Escalation, except for those that only apply to Dose
Escalation, plus the following:

- Required paired pre- and on-treatment tumor biopsies for participants in Cohorts
A1-A5, B1, and B2 with metastases that are safely accessible as determined by the
investigator

- In South Korea: Must have received exactly 2 prior lines of treatment for advanced or
metastatic breast cancer

- In the rest of the world: No more than 1 prior line of treatment for advanced or
metastatic breast cancer (not applicable to Cohort X)

Plus the following criteria:

- Cohorts B1 and B2: No prior treatment with CDK4/6 inhibitor

- Cohorts A1, A3, A5, B1, C1, and C2 only: Postmenopausal status

- Cohorts A2, A4, and B2 only: Participants not defined as postmenopausal; Age less than
(<)56 years who have medical menopause on LHRH agonist (on stable dose =4 weeks)

- No prior treatment with an oral selective estrogen receptor degrader (SERD)

- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use non-hormonal contraceptive methods with a failure
rate of <1% per year during the treatment period and for 40 days after the last dose
of GDC-9545, and agreement to refrain from donating eggs during this same period

- Cohort X only: Participants enrolled on Studies GO29656 or GO29642 and received
clinical benefit from GDC-0927 or GDC-0810

- Hematology, chemistry, and urinalysis collected 72 hours before Cycle 1, Day 1 deemed
acceptable for dosing by the investigator

- No other endocrine therapy, targeted therapy, or chemotherapy after last dose of
GDC-0927 or GDC-0810
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria for Dose Escalation:

- Known brain metastases that are untreated, symptomatic, or require therapy to control
symptoms

- Current treatment with any systemic anti-cancer therapies for advanced disease (not
applicable to Cohort X participants currently receiving GDC-0810 or GDC-0927)

- Concurrent treatment with warfarin or phenytoin

- 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, chronic diarrhea, short bowel syndrome, or major
upper gastrointestinal (GI) surgery including gastric resection

- Known human immunodeficiency virus (HIV) infection

- Known clinically significant history of liver disease consistent with Child-Pugh Class
B or C, including active viral or other hepatitis (e.g., hepatitis B or hepatitis C
virus), current alcohol abuse, or cirrhosis

- Major surgery within 4 weeks prior to enrollment

- Radiation therapy within 2 weeks prior to enrollment

- 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

- Inability or unwillingness to swallow tablets or capsules (only applies to Dose
Escalation)

- Any serious medical condition or abnormality in clinical laboratory tests that, in the
investigator's judgment, precludes the patient's safe participation in and completion
of the study (only applies to Dose Escalation)

- 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 using Fridericia's formula (QTcF) greater than (>)470
milliseconds (ms) 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

Exclusion Criteria for Dose Expansion:

Same criteria as above for Dose Escalation, except for those that only apply to Dose
Escalation, plus the following criteria:

- Pregnant, lactating, or breastfeeding

- Additional exclusion criteria for Cohort B (Phase 1b cohort): History of venous
thromboembolic event requiring therapeutic anticoagulation

- Additional exclusion criteria for Cohorts C1 and C2 only: Current treatment with
medications that are well known to decrease heart rate, including beta blockers

Study design
Purpose of the study
Treatment
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
Other
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
Recruitment hospital [1] 0 0
St Vincent's Hospital Sydney - Darlinghurst
Recruitment hospital [2] 0 0
Cabrini Hospital Malvern - Malvern
Recruitment hospital [3] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3144 - Malvern
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
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
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
Korea, Republic of
State/province [5] 0 0
Gyeonggi-do
Country [6] 0 0
Korea, Republic of
State/province [6] 0 0
Seoul
Country [7] 0 0
Spain
State/province [7] 0 0
Barcelona
Country [8] 0 0
Spain
State/province [8] 0 0
Guipuzcoa
Country [9] 0 0
Spain
State/province [9] 0 0
Madrid
Country [10] 0 0
Spain
State/province [10] 0 0
Valencia
Country [11] 0 0
United Kingdom
State/province [11] 0 0
London
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Sutton

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 safety, pharmacokinetic (PK), pharmacodynamic (PD) activity, and
preliminary anti-tumor activity of GDC-9545 as a single agent and in combination with
palbociclib and/or luteinizing hormone-releasing hormone (LHRH) agonist in participants with
advanced or metastatic estrogen receptor (ER)-positive (human epidermal growth factor
receptor 2 [HER2]-negative) breast cancer.
Trial website
https://clinicaltrials.gov/show/NCT03332797
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: GO39932 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/NCT03332797