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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02964507




Registration number
NCT02964507
Ethics application status
Date submitted
12/11/2016
Date registered
16/11/2016
Date last updated
27/05/2020

Titles & IDs
Public title
Dose Escalation and Expansion Study of GSK525762 in Combination With Fulvestrant in Subjects With Hormone Receptor-positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Advanced or Metastatic Breast Cancer
Scientific title
A Phase I/II Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK525762 in Combination With Fulvestrant in Subjects With HR+/HER2- Advanced or Metastatic Breast Cancer
Secondary ID [1] 0 0
2016-003074-40
Secondary ID [2] 0 0
201973
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK525762
Treatment: Drugs - Placebo
Treatment: Drugs - Fulvestrant

Experimental: GSK525762 + Fulvestrant (Phase I) - In Phase I, all subjects will receive treatment with GSK525762 in combination with fulvestrant. Dosing will be continued until unacceptable toxicity, progression of disease, death, or withdrawal of consent.

Experimental: GSK525762 + Fulvestrant (Phase II) - Subjects will receive treatment with GSK525762 in combination with fulvestrant, at a GSK525762-dose level selected from Phase I. Dosing will be continued until unacceptable toxicity, progression of disease, death, or withdrawal of consent.

Placebo Comparator: Placebo + Fulvestrant (Phase II) - In Phase II, subjects will receive treatment with placebo in combination with fulvestrant. Dosing will be continued until unacceptable toxicity, progression of disease, death, or withdrawal of consent.


Treatment: Drugs: GSK525762
For Phase I, GSK525762 will be available as 5 mg and 25 mg oral tablets. Subjects will be initially dosed at 60 mg daily (Dose Level 1). Further subjects will be dosed based on the dose limiting toxicity rate, at a higher 'Dose Level 2' (or still higher, based on PK data), same 'Dose Level 1', or lower 'Dose Level 1'.

Treatment: Drugs: Placebo
Placebo will match GSK525762 tablets, and will be provided in Phase II only. Dosing will be done until unacceptable toxicity, progression of disease, death, or withdrawal of consent.

Treatment: Drugs: Fulvestrant
Fulvestrant will be supplied as a solution for injection in a prefilled syringe, at a strength of 250 milligrams (mg) per 5 milliliters (mL), for slow intramuscular (IM) injection into the buttocks. Two 5 mL injections (total 500 mg of fulvestrant) will be administered, one in each buttock, on Day 1, Day 15, Day 29, and once monthly thereafter.

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

Outcomes
Primary outcome [1] 0 0
Phase I: Number of subjects with adverse events (AE) and serious adverse events (SAE), for the determination of recommended Phase II dose of GSK525762 - An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.
Timepoint [1] 0 0
From Day 1 until end of treatment (approximately 15 months)
Primary outcome [2] 0 0
Phase I: Number of subjects with dose limiting toxicities (DLT) - An event will be considered a DLT if it occurs within the first 28 days of treatment and meets at least one of the DLT criteria.
Timepoint [2] 0 0
From Day 1 until end of treatment (approximately 15 months)
Primary outcome [3] 0 0
Phase I: Number of subjects with dose reductions or delays, for the determination of recommended Phase II dose of GSK525762 - Subjects who experience toxicity may require dose delay and/or reduction of dose based on which phase II dose will be determined.
Timepoint [3] 0 0
From Day 1 until end of treatment (approximately 15 months)
Primary outcome [4] 0 0
Phase I: Overall response rate (ORR) - ORR is defined as complete response (CR) rate plus partial response (PR) rate.
Timepoint [4] 0 0
From Day 1 until end of treatment (approximately 15 months)
Primary outcome [5] 0 0
Phase I: Plasma concentration of GSK525762, for the determination of recommended Phase II dose of GSK525762 - Subjects will be instructed to withhold their dose of orally administered study drugs, including GSK525762 and fulvestrant, until after the pre-dose pharmacokinetic blood sample is collected.
Timepoint [5] 0 0
Day 1 of Weeks 1, 3, 5, 9, 16, and 24
Primary outcome [6] 0 0
Phase I: Plasma concentration of fulvestrant, for the determination of recommended Phase II dose of GSK525762 - Blood samples for PK analysis will be collected at the indicated timepoints.
Timepoint [6] 0 0
Day 1 of Weeks 1, 3, 5, 9, 16, and 24
Primary outcome [7] 0 0
Phase II: Progression free survival (PFS) - PFS will be defined as the time from study treatment start until the first date of either disease progression or death due to any cause.
Timepoint [7] 0 0
From Day 1 until disease progression or death (approximately 16 months)
Secondary outcome [1] 0 0
Phase I: Number of subjects with AEs or SAEs, as a measure of safety and tolerability - An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.
Timepoint [1] 0 0
From Day 1 until end of treatment (approximately 15 months)
Secondary outcome [2] 0 0
Phase I: Number of subjects with dose reductions or delays, as a measure of safety and tolerability - Subjects who experience toxicity may require dose delay and/or reduction of dose which will be determined as a measure of safety and tolerability.
Timepoint [2] 0 0
From Day 1 until end of treatment (approximately 15 months)
Secondary outcome [3] 0 0
Phase I: Number of subjects withdrawn due to toxicity - To determine the safety, tolerability, and maximum tolerated dose (MTD) of GSK525762, when given in combination with fulvestrant in women with HR+/HER2- advanced or metastatic breast cancer.
Timepoint [3] 0 0
From Day 1 until end of treatment (approximately 15 months)
Secondary outcome [4] 0 0
Phase I: Number of subjects with abnormality in hematology parameters - hematology parameters included white blood cells (WBCs), hemoglobin, platelet count, neutrophils, lymphocytes, monocytes, eosinophils and basophils.
Timepoint [4] 0 0
From Day 1 until end of treatment (approximately 15 months)
Secondary outcome [5] 0 0
Phase I: Number of subjects with abnormality in clinical chemistry parameters - Clinical chemistry parameters included sodium, potassium, chloride, total carbondioxide, blood urea nitrogen, creatinine, fasting glucose, magnesium, calcium, total protein, albumin, bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase.
Timepoint [5] 0 0
From Day 1 until end of treatment (approximately 15 months)
Secondary outcome [6] 0 0
Phase I: Number of subjects with abnormality in urinalysis parameters - Urianalysis parameters included Specific gravity, pH, glucose, protein, blood, and ketones by dipstick Microscopic examination (if urinalysis is abnormal, if available at participating site) Urine hCG pregnancy test (only for women of child bearing potential.
Timepoint [6] 0 0
From Day 1 until end of treatment (approximately 15 months)
Secondary outcome [7] 0 0
Phase I: Number of subjects with abnormality in systolic and diastolic blood pressure - Systolic and diastolic blood pressure should be measured in semi-supine position after 5 minutes rest
Timepoint [7] 0 0
From Day 1 until end of treatment (approximately 15 months)
Secondary outcome [8] 0 0
Phase I: Number of subjects with abnormality in pulse rate - Pulse rate should be measured in semi-supine position after 5 minutes rest
Timepoint [8] 0 0
From Day 1 until end of treatment (approximately 15 months)
Secondary outcome [9] 0 0
Phase I: Number of subjects with abnormality in respiratory rate - Respiratory rate should be measured in semi-supine position after 5 minutes rest
Timepoint [9] 0 0
From Day 1 until end of treatment (approximately 15 months)
Secondary outcome [10] 0 0
Phase I: Number of subjects with abnormality in electrocardiogram (ECG) - Twelve-lead ECGs will be obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTcF intervals.
Timepoint [10] 0 0
From Day 1 until end of treatment (approximately 15 months)
Secondary outcome [11] 0 0
Phase I: Number of subjects with abnormality in any cardiotoxicity parameters - Cardiotoicity parameters included troponin (I or T at local laboratory), NT-proBNP, Total Cholesterol, low density lipoprotein (LDL), high density lipoprotien (HDL) and triglycerides.
Timepoint [11] 0 0
From Day 1 until end of treatment (approximately 15 months)
Secondary outcome [12] 0 0
Phase I: Number of subjects with abnormality in gastrointestinal parameters - During clinical studies, medical history, physical examination (including weight) and clinical laboratory assessments will be used to identify and assess toxicity in the GI tract.
Timepoint [12] 0 0
From Day 1 until end of treatment (approximately 15 months)
Secondary outcome [13] 0 0
Phase I: Disease control rate (DCR) - DCR is defined as CR plus PR plus stable disease [SD] rate.
Timepoint [13] 0 0
From Day 1 until end of treatment (approximately 15 months)
Secondary outcome [14] 0 0
Phase I: Duration of response - Duration of response is the subset of subjects who show a confirmed CR or PR, the time from first documented evidence of CR or PR until the first documented sign of disease progression or death.
Timepoint [14] 0 0
From Day 1 until disease progression or death (approximately 15 months)
Secondary outcome [15] 0 0
Phase I: PFS - Progression-free survival (PFS) will be defined as the time from study treatment start until the first date of either disease progression or death due to any cause.
Timepoint [15] 0 0
From Day 1 until disease progression or death (approximately 15 months)
Secondary outcome [16] 0 0
Phase I: Plasma concentration of GSK525762 and its metabolites, as a measure of drug exposure - Blood samples for PK analysis will be collected at the indicated timepoints.
Timepoint [16] 0 0
Day 1 of Weeks 1, 3, 5, 9, 16, and 24
Secondary outcome [17] 0 0
Phase I: Plasma concentration of fulvestrant, as a measure of drug exposure - Blood samples for PK analysis will be collected at the indicated timepoints.
Timepoint [17] 0 0
Day 1 of Weeks 1, 3, 5, 9, 16, and 24
Secondary outcome [18] 0 0
Phase II: Overall Survival (OS) - For the analysis of OS, the last date of known contact will be used for those subjects who have not died at the time of analysis; such subjects will be considered censored.
Timepoint [18] 0 0
From Day 1 until death (approximately 16 months)
Secondary outcome [19] 0 0
Phase II: ORR - ORR is defined as the percentage of subjects with a confirmed CR or a PR at any time.
Timepoint [19] 0 0
From Day 1 until end of treatment (approximately 16 months)
Secondary outcome [20] 0 0
Phase II: DCR - DCR is defined as CR plus PR plus stable disease [SD] rate.
Timepoint [20] 0 0
From Day 1 until end of treatment (approximately 16 months)
Secondary outcome [21] 0 0
Phase II: Plasma concentration of GSK525762 and its metabolites, as a measure of drug exposure - Blood samples for PK analysis will be collected at the indicated timepoints.
Timepoint [21] 0 0
Day 1 of Weeks 1, 5, 9, 16, and 24
Secondary outcome [22] 0 0
Phase II: Plasma concentration of fulvestrant, as a measure of drug exposure - Blood samples for PK analysis will be collected at the indicated timepoints.
Timepoint [22] 0 0
Day 1 of Weeks 1, 5, 9, 16, and 24

Eligibility
Key inclusion criteria
- Written informed consent provided.

- Females 18 years old and greater (at the time of written consent)

- Histologically or cytologically confirmed diagnosis of advanced or metastatic
adenocarcinoma of the breast.

- Documentation of ER-positive and/or progesterone receptor (PR)-positive tumor (>=1%
positive stained tumor cell nuclei) based on local testing of the most recent tumor
biopsy, using an assay consistent with local standards.

- Documentation of HER2-negative tumor based on local testing of the most recent tumor
biopsy. At the time of writing, HER2-negative tumor is defined as immunohistochemistry
(IHC) score of 0 or 1+, or negative by in situ hybridization defined as a
HER2/chromosome enumeration probe 17 (CEP17) ratio <2 or for single probe assessment
of an average HER2 copy number <4.

- Provision of mandatory screening fresh tumor biopsy sample during the screening
period.

1. Screening biopsy can be waived if a biopsy was collected within 3 months prior to
first dose of study drug and was collected after the last anti-cancer treatment
before coming into this study.

2. Subjects with inaccessible site of biopsy or who have a significant medical risk
of obtaining the biopsy should be discussed with the Medical Monitor if they can
qualify.

3. Bone biopsies are not acceptable. Biopsies should be obtained from bone with
metastatic soft-tissue component. Subjects with bone only disease may be enrolled
upon review by Medical Monitor.

- History of prior therapy that satisfies one of the following criteria:

1. Aromatase inhibitor (AI) failures: Disease that relapsed during treatment or
within 12 months of completion of adjuvant therapy with an AI, OR disease that
progressed during treatment with an AI for advanced/metastatic disease. Prior
ovarian suppression and/or tamoxifen are allowed as long as other criteria are
met.

2. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitor plus AI failures: Disease that
progressed on a CDK4/6 inhibitor plus AI, for advanced/metastatic disease with a
minimum duration of treatment of 12 months (>=12 months) with CDK4/6 inhibitor
plus AI. Subjects with either measurable disease or bone only disease are
allowed. Prior ovarian suppression and/or tamoxifen are allowed as long as other
criteria are met.

- Documented progression on last line of systemic anti-cancer therapy with CDK4/6
inhibitor + AI is required.

- Any menopausal status.

- Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
criteria is required except for subjects with bone only disease.

- All prior treatment- related toxicities must be National Cancer Institute-Common
Terminology Criteria for Adverse Events (NCI-CTCAE) version 4 <= Grade 1 (except
alopecia (permitted at any grade) and peripheral neuropathy (permitted at <= Grade 2)
at the time of treatment allocation.

- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 1.

- Adequate organ function.

- Able to swallow and retain orally administered medication.

- A female subject is eligible to participate if she is of: i) Non-childbearing
potential and agrees to use one of the contraception methods, from the time of the
screening pregnancy test until 7 months after the last dose of study medication. ii)
Negative serum pregnancy test <=7 days prior to first study drug dose. iii) Female
subjects who are lactating must discontinue nursing prior to the first dose of study
treatment and must refrain from nursing throughout the treatment period and for at
least 28 days following the last dose of study treatment.
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior therapy with any Bromodomain and extra-terminal (BET) inhibitor, any selective
estrogen receptor degrader (SERD) including fulvestrant, or inhibitors of the
Phosphoinositide-3-kinase (PI3K)/ serine/threonine-specific protein kinase
(AKT)/Mammalian Target of Rapamycin (mTOR) pathway.

- Prior therapy with more than one line of cytotoxic chemotherapy following diagnosis of
advanced/metastatic disease.

- More than or equal to 3 lines of systemic anti-cancer therapy in the advanced or
metastatic setting.

- Recent prior therapy, defined as:

1. Any investigational or approved non-biologic anti-cancer drug within 14 days or
five half-life (whichever is greater) prior to the first dose of GSK525762 and
fulvestrant.

2. Any nitrosoureas or mitomycin C within 42 days prior to the first dose of
GSK525762 and fulvestrant

3. Any anti-cancer biologic agents within 42 days prior to the first dose of
GSK525762 and fulvestrant

4. Any radiotherapy within 14 days prior to the first dose of GSK525762 and
fulvestrant. If the subject received radiotherapy <90 days prior to study
treatment, the irradiated lesion cannot be the only lesion used for evaluating
response.

5. Any major surgery within 28 days prior to the first dose of GSK525762 and
fulvestrant

- Concomitant active malignancy other than HR+/HER2- breast cancer

- Therapeutic-dose anticoagulation (e.g., warfarin, low-molecular weight heparin [LMWH],
or novel oral anticoagulants) must be discontinued and coagulation parameters must be
normalized prior to the first dose of GSK525762 and fulvestrant. Prophylactic
anticoagulation, with low doses (per standard practice) of agents such as LMWH, direct
thrombin inhibitors, or factor Xa inhibitors is permitted.

- Current use of a prohibited medication or planned use of any forbidden medications
during treatment with GSK525762 and fulvestrant. This includes medications with
significant risk of Torsades de pointes as well as those that are potent inducers or
inhibitors of CYP3A4 enzymes.

- Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated
respiratory, hepatic, renal, cardiac disease, or clinically significant bleeding
episodes). Any serious and/or unstable pre-existing medical (aside from malignancy),
psychiatric disorder, or other conditions that could interfere with subject's safety,
obtaining informed consent or compliance to the study procedures, in the opinion of
the Investigator.

1. Systolic blood pressure higher than 150 millimeters of mercury (mmHg) or
diastolic blood pressure higher than 90 mmHg found on 2 separate occasions
separated by 1 week, despite adequate therapy, will be defined as uncontrolled
hypertension.

2. Uncontrolled diabetes mellitus (despite therapeutic; compliance to intervention)
as defined by a hemoglobin A1c (HbA1c) level more than 8% and/or occurrence of
more than two episodes of ketoacidosis in the 12 months prior to the first dose
of study drug.

- Subjects with advanced/metastatic, symptomatic, visceral spread, that are at risk of
life-threatening complications in the short term including subjects with massive
uncontrolled effusions (pleural, pericardial, peritoneal), pulmonary lymphangitis, and
over 50% of liver involvement in metastases.

- Symptomatic or untreated leptomeningeal or brain metastases or spinal cord
compression.

- Cardiac abnormalities as evidenced by any of the following: Baseline QT interval
corrected by Fridericia's formula (QTcF) interval >=480 milliseconds (msec);
Clinically significant conduction abnormalities or arrhythmias; Presence of cardiac
pacemaker or defibrillator with a paced ventricular rhythm limiting electrocardiogram
analysis; History or evidence of current >=Class II congestive heart failure as
defined by New York Heart Association (NYHA); History of acute coronary syndromes
(including unstable angina and myocardial infarction), coronary angioplasty, or
stenting within the past 3 months. Subjects with a history of stent placement
requiring ongoing antithrombotic therapy (e.g., clopidogrel, prasugrel) will not be
permitted to enroll; Clinically significant cardiomegaly, ventricular hypertrophy, or
cardiomyopathy.

- Current active liver or biliary disease (with the exception of Gilbert's syndrome or
asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease
per investigator assessment).

- Presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test
result at screening.

- History of known human immunodeficiency virus (HIV) infection.

- Any serious known immediate or delayed hypersensitivity reaction(s) to GSK525762 or
fulvestrant, or idiosyncrasy to drugs chemically related to the investigational drugs.

- Hemoptysis >1 teaspoon in 24 hours within the last 28 days.

- Concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) (except for cases
where NSAIDs provide benefit over other analgesics and in these cases, consideration
should be given to the prophylactic administration of a proton pump inhibitor) and
high dose aspirin (allowed up to <=100 milligrams orally daily).

- Subjects with history of known bleeding disorder(s) including clinically significant
hemorrhage (e.g., gastrointestinal, neurologic), within the past 6 months.

- Any clinically significant gastrointestinal abnormalities that may alter absorption,
such as malabsorption syndrome, chronic gastrointestinal disease, or major resection
of the stomach and/or bowels that could preclude adequate absorption of the study
medication.

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
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not 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,SA,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Port Macquarie
Recruitment hospital [2] 0 0
GSK Investigational Site - Bedford Park
Recruitment hospital [3] 0 0
GSK Investigational Site - Heidelberg
Recruitment postcode(s) [1] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [2] 0 0
5042 - Bedford Park
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Louisiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Rhode Island
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
Canada
State/province [15] 0 0
Quebec
Country [16] 0 0
France
State/province [16] 0 0
Bordeaux Cedex
Country [17] 0 0
France
State/province [17] 0 0
Saint-Herblain cedex
Country [18] 0 0
France
State/province [18] 0 0
Saint-Herblain
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Gyeonggi-do
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Seoul
Country [21] 0 0
Spain
State/province [21] 0 0
A Coruna
Country [22] 0 0
Spain
State/province [22] 0 0
Barcelona
Country [23] 0 0
Spain
State/province [23] 0 0
Lerida
Country [24] 0 0
Spain
State/province [24] 0 0
Madrid
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Lancashire
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Middlesex
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Nottinghamshire
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Glasgow
Country [29] 0 0
United Kingdom
State/province [29] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a combination Phase I and Phase II study, with an aim to evaluate the combination of
GSK525762 and fulvestrant in women with HR+/HER2- advanced or metastatic breast cancer, who
have disease that has progressed after prior treatment with at least one line of endocrine
therapy.

The objectives of the study are to first identify, in open-label single-arm Phase I, a
recommended Phase II dose of GSK525762 that may be combined safely with fulvestrant. Phase I
will follow a modified toxicity probability interval (mTPI) design, and a sentinel group will
be evaluated first for dose-limiting toxicity and further expanded to collect additional
safety data. This will be followed by a double-blind, randomized controlled Phase II, to
identify the clinical activity of the two study treatments when given in combination. The
composition of Phase II will be selected at the end of Phase I.

Approximately, up to 140 subjects and 154 subjects will receive study treatment in Phase I
and Phase II respectively. A completed subject will be one who is followed until death.
Trial website
https://clinicaltrials.gov/show/NCT02964507
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications