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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02964507
Ethics application status
Date submitted
12/11/2016
Date registered
16/11/2016

Titles & IDs
Public title
Dose Escalation and Expansion Study of GSK525762 in Combination With Fulvestrant in Participants 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 Hormone Receptor-positive/HER2-negative (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) -

Experimental: GSK525762 + Fulvestrant (Phase II) -

Placebo comparator: Placebo + Fulvestrant (Phase II) -


Treatment: Drugs: GSK525762
GSK525762 will be administered.

Treatment: Drugs: Placebo
Placebo will be administered.

Treatment: Drugs: Fulvestrant
Fulvestrant will be administered.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [1] 0 0
Up to 3 year and 8 months
Primary outcome [2] 0 0
Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)
Timepoint [2] 0 0
Up to 28 days
Primary outcome [3] 0 0
Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays
Timepoint [3] 0 0
Up to 3 year and 8 months
Primary outcome [4] 0 0
Phase I: Objective Response Rate-Investigator Assessment
Timepoint [4] 0 0
Up to 3 year and 8 months
Primary outcome [5] 0 0
Phase I: Plasma Concentration of GSK525762
Timepoint [5] 0 0
Day 1: Pre-dose, 0.5, 1, 3 hours on Weeks 1 and 3; Day 1: Pre-dose, 0.5-1, 4-8 hours on Week 5; Day 1: Pre-dose, 0.5-1 hour on Weeks 9, 17, 25
Primary outcome [6] 0 0
Phase II: Progression Free Survival (PFS)
Timepoint [6] 0 0
Up to 3 year and 8 months
Secondary outcome [1] 0 0
Phase I: Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment
Timepoint [1] 0 0
Up to 4 year and 4 months
Secondary outcome [2] 0 0
Phase I: Disease Control Rate (DCR)
Timepoint [2] 0 0
Up to 3 year and 8 months
Secondary outcome [3] 0 0
Phase I: Duration of Response (DoR)
Timepoint [3] 0 0
Up to 3 year and 8 months
Secondary outcome [4] 0 0
Phase I: Progression-free Survival (PFS)
Timepoint [4] 0 0
Up to 3 year and 8 months
Secondary outcome [5] 0 0
Phase I: Plasma Concentration of GSK3529246
Timepoint [5] 0 0
Day 1: Pre-dose, 0.5, 1, 3 hours on Weeks 1 and 3; Day 1: Pre-dose, 0.5-1, 4-8 hours on Week 5, Day 1: pre-dose, 0.5-1 hour on Weeks 9, 17, 25
Secondary outcome [6] 0 0
Phase I: Plasma Concentration of Fulvestrant
Timepoint [6] 0 0
Day 1: Pre-dose on Weeks 1, 3, 5, 9, 17, 25
Secondary outcome [7] 0 0
Phase II: Overall Survival (OS)
Timepoint [7] 0 0
Up to 3 year and 8 months
Secondary outcome [8] 0 0
Phase II: Overall Response Rate (ORR)
Timepoint [8] 0 0
Up to 3 year and 8 months
Secondary outcome [9] 0 0
Phase II: Disease Control Rate (DCR)
Timepoint [9] 0 0
Up to 3 year and 8 months
Secondary outcome [10] 0 0
Phase II: Plasma Concentration of GSK525762 and GSK3529246
Timepoint [10] 0 0
Day 1: Pre-dose, 0.5, 1, 3 hours on Weeks 1 and 3; Day 1: Pre-dose, 0.5-1, 4-8 hours on Week 5, Day 1: Pre-dose, 0.5-1 hour on Weeks 9, 17, 25
Secondary outcome [11] 0 0
Phase II: Plasma Concentration of Fulvestrant
Timepoint [11] 0 0
Day 1: Pre-dose on Weeks 1, 3, 5, 9, 17, 25

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 estrogen receptor (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 as per most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines. 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: a. 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; b. Participants 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; c. Bone biopsies are not acceptable. Biopsies should be obtained from bone with metastatic soft-tissue component. Participants with bone only disease may be enrolled upon review by Medical Monitor.
* History of prior therapy that satisfies one of the following criteria: a. 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; b. 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. Participants 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 plus AI is required.
* Any menopausal status.
* Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria is required except for participants 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 participant is eligible to participate if she is of: i) Non-childbearing potential. ii) Child-bearing potential and agrees to use one of the contraception methods. iii) Negative serum pregnancy test <=7 days prior to first study drug dose. iv) Female participants 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
Sex
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: a. 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. b. Any nitrosoureas or mitomycin C within 42 days prior to the first dose of GSK525762 and fulvestrant c. Any anti-cancer biologic agents within 42 days prior to the first dose of GSK525762 and fulvestrant. d. Any radiotherapy within 14 days prior to the first dose of GSK525762 and fulvestrant. If the participant received radiotherapy <90 days prior to study treatment, the irradiated lesion cannot be the only lesion used for evaluating response.

e. 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 Cytochrome P3A4 (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 participant's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator. a) 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. b) 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.
* Participants with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term including participants with massive uncontrolled effusions (pleural, pericardial, peritoneal), pulmonary lymphangitis, and over 50 percent (%) 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. Participants 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).
* Participants 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 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/09/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/07/2021
Sample size
Target
Accrual to date
Final
124
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
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Rhode Island
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Washington
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
Canada
State/province [14] 0 0
Quebec
Country [15] 0 0
France
State/province [15] 0 0
Bordeaux Cedex
Country [16] 0 0
France
State/province [16] 0 0
Saint-Herblain cedex
Country [17] 0 0
France
State/province [17] 0 0
Saint-Herblain
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Gyeonggi-do
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Seoul
Country [20] 0 0
Spain
State/province [20] 0 0
A Coruna
Country [21] 0 0
Spain
State/province [21] 0 0
Barcelona
Country [22] 0 0
Spain
State/province [22] 0 0
Lerida
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Lancashire
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Middlesex
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Nottinghamshire
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Glasgow
Country [27] 0 0
United Kingdom
State/province [27] 0 0
London

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
GSK will assess requests from qualified researchers for anonymized individual patient-level data (IPD) and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Anonymized IPD is made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
Available to whom?
Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02964507