Clinical trial using GSK525762 in combination with fulvestrant in subjects with breast cancer.

Phase 1

• Conditions: ER-positive Breast Cancer; MedDRA version: 20.0Level: LLTClassification code 10070575Term: Estrogen receptor positive breast cancerSystem Organ Class: 100000115074; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-003074-40-FR
• Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-08-10
• Study Completion: 2021-07-19
• Last Update Posted: 4 April 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 123

Inclusion Criteria

1. Written informed consent provided
2. Females 18 years old and greater (at the time of written consent)
3. Histologically or cytologically confirmed diagnosis of advanced or metastatic adenocarcinoma of the breast.
4. Documentation of ER-positive and/or PR-positive tumor based on local testing of the most recent tumor biopsy
5. Documentation of HER2-negative tumor based on local testing of the most recent tumor biopsy
6. History of prior therapy that satisfies one of the following criteria:
a. 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.CDK 4/6 inhibitor plus letrozole failures: disease that progressed during treatment with the combination of a CDK4/6 inhibitor plus letrozole, for advanced/metastatic disease. Prior ovarian suppression and/or tamoxifen are allowed as long as other criteria are met.
7. Documented progression on last line of systemic anti-cancer therapy is required.
8. Any menopausal status
9. Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
10. All prior treatment- related toxicities must be NCI-CTCAE v4 < Grade 1 (except alopecia (permitted at any grade) and peripheral neuropathy (permitted at < Grade 2) at the time of treatment allocation
11. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 1
12. Adequate organ function
13. Able to swallow and retain orally administered medication
14. A female subject is eligible to participate if she is of:
- non-childbearing potential
- child-bearing 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
- negative serum pregnancy test <7 days prior to first study drug dose - 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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 195
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 105

Exclusion Criteria

1. Prior therapy with any BET inhibitor, any selective estrogen receptor degrader (SERD) including fulvestrant, or inhibitors of the PI3K/AKT/mTOR pathway.
2.Prior therapy with more than one line of cytotoxic chemotherapy following diagnosis of advanced/metastatic disease.
3. =3 lines of systemic anti-cancer therapy in the advanced or metastatic setting
4.Recent prior therapy, defined as:
· 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.
· Any nitrosoureas or mitomycin C within 42 days prior to the first dose of GSK525762 and fulvestrant
· Any anti-cancer biologic agents within 42 days prior to the first dose of GSK525762 and fulvestrant
· 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.
· Any major surgery within 28 days prior to the first dose of GSK525762 and fulvestrant
5.Concomitant active malignancy other than ER+BC
6.Therapeutic-dose anticoagulation must be discontinued and coagulation parameters must be normalized prior to the first dose of GSK525762 and fulvestrant. Prophylactic anticoagulation is permitted.
7.Current use of a prohibited medication or planned use of any forbidden medications during treatment with GSK525762 and fulvestrant.
8.Evidence of severe or uncontrolled systemic diseases. 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.
9.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.
10.Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression.
11. Cardiac abnormalities as evidenced by any of the following:
·Baseline QTcF interval =450 msec
·Clinically significant conduction abnormalities or arrhythmias
·Presence of cardiac pacemaker or defibrillator with a paced ventricular rhythm limiting ECG 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
12.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).
13.Presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test result at screening.
14.History of known HIV infection.
15.Any serious known immediate or delayed hypersensitivity reaction(s) to GSK525762 or fulvestrant, or idiosyncrasy to drugs chemically related to the investigational drugs.
16.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified