NeoplasmsPhase 1NCT02964507
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
A Phase 1 study testing GSK525762 and Fulvestrant in people with Neoplasms, run by GlaxoSmithKline at 38 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Neoplasms
- What is being tested?
- GSK525762 and Fulvestrant
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 124 participants
- Where
- 38 sitesin 7 countries
- Study dates
- 26 Sep 2019to 19 Jul 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
- Any major surgery within 28 days prior to the first dose of GSK525762 and fulvestrant
- Concomitant active malignancy other than HR+/HER2- breast cancer
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- 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.
Trial locations and contacts
38 sites in 7 countries.
38 sites in 7 countries
United States15 sites
GSK Investigational Site
Birmingham, Alabama, 35249
GSK Investigational Site
Chicago, Illinois, 60611
GSK Investigational Site
Gilbert, Arizona, 85234
GSK Investigational Site
Houston, Texas, 77030
GSK Investigational Site
Kansas City, Missouri, 64111
GSK Investigational Site
New Orleans, Louisiana, 70121
GSK Investigational Site
Plantation, Florida, 33324
GSK Investigational Site
Providence, Rhode Island, 02903
GSK Investigational Site
Rochester, Minnesota, 55905
GSK Investigational Site
San Diego, California, 92123
GSK Investigational Site
Scottsdale, Arizona, 85259
GSK Investigational Site
Seattle, Washington, 98101
GSK Investigational Site
St Louis, Missouri, 63110
GSK Investigational Site
The Bronx, New York, 10461
GSK Investigational Site
White Plains, New York, 10601
United Kingdom6 sites
GSK Investigational Site
Glasgow, G12 OYN
GSK Investigational Site
London, EC1M 6BQ
GSK Investigational Site
London, NW1 2PG
GSK Investigational Site
Manchester, Lancashire, M20 4BX
GSK Investigational Site
Northwood, Middlesex, HA6 2RN
GSK Investigational Site
Nottingham, Nottinghamshire, NG5 1PB
Canada5 sites
GSK Investigational Site
Montreal, Quebec, H2L 4M1
GSK Investigational Site
Montreal, Quebec, H3T 1E2
GSK Investigational Site
Ottawa, Ontario, K1H 8L6
GSK Investigational Site
Québec, Quebec, G1S 4L8
GSK Investigational Site
Toronto, Ontario, M5G 2M9
South Korea4 sites
GSK Investigational Site
Gyeonggi-do, 410-769
GSK Investigational Site
Seoul, 120-752
GSK Investigational Site
Seoul, 135-710
GSK Investigational Site
Seoul, 138-736
Australia3 sites
GSK Investigational Site
Bedford Park, South Australia, 5042
GSK Investigational Site
Heidelberg, Victoria, 3084
GSK Investigational Site
Port Macquarie, New South Wales, 2444
Spain3 sites
GSK Investigational Site
A Coruña, 15006
GSK Investigational Site
Barcelona, 8035
GSK Investigational Site
Lleida, 25198
France2 sites
GSK Investigational Site
Bordeaux, 33076
GSK Investigational Site
Saint-Herblain, 44805
About this study
Official 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
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.
- Conditions
- Neoplasms
- Being tested
- GSK525762, Placebo, Fulvestrant
- Keywords
- GSK525762, HR+/HER2- advanced or metastatic breast cancer, mTPI
- Medical subject headings
- Neoplasms, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK525762Drug
GSK525762 will be administered.
PlaceboDrug
Placebo will be administered.
FulvestrantDrug
Fulvestrant will be administered.
| Study group | Role | What they receive |
|---|---|---|
| GSK525762 + Fulvestrant (Phase I) | Experimental | Not described Receives: Drug: GSK525762; Drug: Fulvestrant |
| GSK525762 + Fulvestrant (Phase II) | Experimental | Not described Receives: Drug: GSK525762; Drug: Fulvestrant |
| Placebo + Fulvestrant (Phase II) | Placebo comparator | Not described Receives: Drug: Placebo; Drug: Fulvestrant |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement or is associated with liver injury and impaired liver function. Any other adverse event apart from SAE is considered as non-SAE.
Measured: Up to 3 year and 8 months
Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)
An event was considered DLT if it occurred within first 28 days of treatment and met one of following DLT criteria: Grade3 or greater neutropenia for >=5 days, febrile neutropenia, Grade4 anemia of any duration, Grade4 thrombocytopenia of any duration or Grade3 thrombocytopenia with bleeding, alanine aminotransferase (ALT) >3 times (x) upper limit of normal (ULN)+bilirubin >=2x ULN (>35 % direct) or ALT between 3-5xULN with bilirubin <2xULN but with hepatitis symptoms or rash, Grade3 nausea,vomiting or diarrhea that did not improve within 72hour despite appropriate supportive treatment(s), Grade4 nausea,vomiting,or diarrhea, Grade3 hypertension (uncontrolled despite addition of upto 2 antihypertensive medications), Grade4 hypertension, other Grade3 or greater clinically significant non-hematologic toxicity (including QT duration corrected for heart rate by Fridericia's formula (QTcF), ejection fraction <lower limit of normal (LLN) with an absolute decrease of >10% from Baseline.
Measured: Up to 28 days
Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays
Number of participants with dose reductions and dose interruption or delay due to any reason is presented.
Measured: Up to 3 year and 8 months
Phase I: Objective Response Rate-Investigator Assessment
Objective Response Rate is defined as the percentage of participants who demonstrate a Best Response of confirmed complete response (CR) or partial response (PR), as assessed by the investigator per response evaluation criteria in solid tumors (RECIST) version (v) 1.1 criteria.
Measured: Up to 3 year and 8 months
Phase I: Plasma Concentration of GSK525762
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK525762.
Measured: 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
Phase II: Progression Free Survival (PFS)
PFS is defined as the time (in months) from the date of first dose until the date of first documented progressive disease (PD), as assessed by the investigator per RECIST v1.1 criteria, or date of death due to any cause, whichever occurs first. PD is defined as at least a 20% increase in the sum of the diameters of target lesions taking as a reference the smallest sum of diameters for this study.
Measured: Up to 3 year and 8 months
Secondary outcomes (11)
Phase I: Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment
Number of participants who withdrew due to toxicity and changes in safety assessment including laboratory parameters and vital signs have been presented.
Measured: Up to 4 year and 4 months
Phase I: Disease Control Rate (DCR)
DCR is defined as the percentage of participants in the population with a confirmed complete response (CR), confirmed partial response (PR), or stable disease (SD) lasting >=6 months, as assessed by the investigator per RECIST v1.1 criteria.
Measured: Up to 3 year and 8 months
Phase I: Duration of Response (DoR)
DoR is defined as the time (in months) from date of first documented evidence of confirmed CR or PR to the date of first documented PD, as assessed by the investigator per RECIST v1.1 criteria, or to the date of death due to any cause among participants with a Best overall response (BOR) of confirmed CR or PR.
Measured: Up to 3 year and 8 months
Phase I: Progression-free Survival (PFS)
PFS is defined as the time (in months) from the date of first dose until the date of first documented PD, as assessed by the investigator per RECIST v1.1 criteria, or date of death due to any cause, whichever occurs first. PD is defined as at least a 20% increase in the sum of the diameters of target lesions taking as a reference the smallest sum of diameters for this study.
Measured: Up to 3 year and 8 months
Phase I: Plasma Concentration of GSK3529246
Blood samples were collected at indicated time points for PK analysis of GSK3529246. GSK3529246 is an active metabolite of GSK525762.
Measured: 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
Phase I: Plasma Concentration of Fulvestrant
Blood samples were collected at indicated time points for PK analysis of Fulvestrant.
Measured: Day 1: Pre-dose on Weeks 1, 3, 5, 9, 17, 25
Phase II: Overall Survival (OS)
OS is defined as the interval of time (in months) between the date of first dose and the date of death due to any cause.
Measured: Up to 3 year and 8 months
Phase II: Overall Response Rate (ORR)
ORR is defined as the percentage of participants in the population who demonstrate a BOR of confirmed CR or PR, as assessed by the investigator per RECIST v1.1 criteria.
Measured: Up to 3 year and 8 months
Phase II: Disease Control Rate (DCR)
DCR is defined as the percentage of participants in the population with a confirmed CR, confirmed PR, or SD lasting >=6 months, as assessed by the investigator per RECIST v1.1 criteria.
Measured: Up to 3 year and 8 months
Phase II: Plasma Concentration of GSK525762 and GSK3529246
Blood samples were planned to be collected for PK analysis of GSK525762 and GSK3529246. GSK3529246 is metabolite of GSK525762.
Measured: 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
Phase II: Plasma Concentration of Fulvestrant
Blood samples were planned to be collected for PK analysis of fulvestrant.
Measured: Day 1: Pre-dose on Weeks 1, 3, 5, 9, 17, 25
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2016 (estimated)
- Study start26 Sep 2019
- Primary completion29 Sep 2020
- Study completion19 Jul 2021
Why it stopped: This study has been terminated due to meeting protocol defined futility.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 124 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02964507
- Sponsor's protocol ID
- 201973
- Other IDs
- 2016-003074-40, 2016
- Status last verified
- Aug 2024
- First submitted
- 12 Nov 2016
- Last updated
- 29 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 29 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02964507
- Acronym / sponsor ID
- 201973
- Conditions
- Neoplasms
- Keywords
- GSK525762, HR+/HER2- advanced or metastatic breast cancer, mTPI
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study has been terminated due to meeting protocol defined futility.
- Enrolment
- 124 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 26 Sep 2019 (actual)
- Primary completion
- 29 Sep 2020 (actual)
- Study completion
- 19 Jul 2021 (actual)
- First posted
- 16 Nov 2016 (estimated)
- Results
- Posted 27 Jan 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| GSK525762 + Fulvestrant (Phase I) | Experimental | Drug: GSK525762, Drug: Fulvestrant |
| GSK525762 + Fulvestrant (Phase II) | Experimental | Drug: GSK525762, Drug: Fulvestrant |
| Placebo + Fulvestrant (Phase II) | Placebo comparator | Drug: Placebo, Drug: Fulvestrant |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
- Concomitant active malignancy other than HR+/HER2- breast cancer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK525762GSK525762 will be administered. | Drug | GSK525762 + Fulvestrant (Phase I), GSK525762 + Fulvestrant (Phase II) |
| PlaceboPlacebo will be administered. | Drug | Placebo + Fulvestrant (Phase II) |
| FulvestrantFulvestrant will be administered. | Drug | GSK525762 + Fulvestrant (Phase I), GSK525762 + Fulvestrant (Phase II), Placebo + Fulvestrant (Phase II) |
Primary outcome
Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to 3 year and 8 months
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement or is associated with liver injury and impaired liver function. Any other adverse event apart from SAE is considered as non-SAE.
Phase I: Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: Up to 28 days
An event was considered DLT if it occurred within first 28 days of treatment and met one of following DLT criteria: Grade3 or greater neutropenia for >=5 days, febrile neutropenia, Grade4 anemia of any duration, Grade4 thrombocytopenia of any duration or Grade3 thrombocytopenia with bleeding, alanine aminotransferase (ALT) >3 times (x) upper limit of normal (ULN)+bilirubin >=2x ULN (>35 % direct) or ALT between 3-5xULN with bilirubin <2xULN but with hepatitis symptoms or rash, Grade3 nausea,vomiting or diarrhea that did not improve within 72hour despite appropriate supportive treatment(s), Grade4 nausea,vomiting,or diarrhea, Grade3 hypertension (uncontrolled despite addition of upto 2 antihypertensive medications), Grade4 hypertension, other Grade3 or greater clinically significant non-hematologic toxicity (including QT duration corrected for heart rate by Fridericia's formula (QTcF), ejection fraction <lower limit of normal (LLN) with an absolute decrease of >10% from Baseline.
Phase I: Number of Participants With Dose Reductions and Dose Interruption/Delays
Time frame: Up to 3 year and 8 months
Number of participants with dose reductions and dose interruption or delay due to any reason is presented.
Phase I: Objective Response Rate-Investigator Assessment
Time frame: Up to 3 year and 8 months
Objective Response Rate is defined as the percentage of participants who demonstrate a Best Response of confirmed complete response (CR) or partial response (PR), as assessed by the investigator per response evaluation criteria in solid tumors (RECIST) version (v) 1.1 criteria.
Phase I: Plasma Concentration of GSK525762
Time frame: 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
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK525762.
Phase II: Progression Free Survival (PFS)
Time frame: Up to 3 year and 8 months
PFS is defined as the time (in months) from the date of first dose until the date of first documented progressive disease (PD), as assessed by the investigator per RECIST v1.1 criteria, or date of death due to any cause, whichever occurs first. PD is defined as at least a 20% increase in the sum of the diameters of target lesions taking as a reference the smallest sum of diameters for this study.
11 secondary outcomes
Phase I: Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment
Time frame: Up to 4 year and 4 months
Phase I: Disease Control Rate (DCR)
Time frame: Up to 3 year and 8 months
Phase I: Duration of Response (DoR)
Time frame: Up to 3 year and 8 months
Phase I: Progression-free Survival (PFS)
Time frame: Up to 3 year and 8 months
Phase I: Plasma Concentration of GSK3529246
Time frame: 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
Phase I: Plasma Concentration of Fulvestrant
Time frame: Day 1: Pre-dose on Weeks 1, 3, 5, 9, 17, 25
Phase II: Overall Survival (OS)
Time frame: Up to 3 year and 8 months
Phase II: Overall Response Rate (ORR)
Time frame: Up to 3 year and 8 months
Phase II: Disease Control Rate (DCR)
Time frame: Up to 3 year and 8 months
Phase II: Plasma Concentration of GSK525762 and GSK3529246
Time frame: 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
Phase II: Plasma Concentration of Fulvestrant
Time frame: Day 1: Pre-dose on Weeks 1, 3, 5, 9, 17, 25
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
38 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK525762 and Fulvestrant in people with Neoplasms, run by GlaxoSmithKline at 38 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States, United Kingdom, Canada, South Korea, Australia and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jan 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: Up to 3 year and 8 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Aug 2024.