A Phase 1 interventional study of Afuresertib and Enzalutamide in Cancer, sponsored by GlaxoSmithKline. Withdrawn. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2016-10-06.
Sponsored by GlaxoSmithKline · Phase 1, Interventional, and Treatment
This study is being conducted to characterize the safety and recommended phase 2 dose (RP2D) of combining afuresertib, independently with 2 approved drugs: enzalutamide (Xtandi®, "Xtandi is a trademark of Astellas Pharma, Inc." ) and abiraterone (Zygita®, "Zytiga is a trademark of Janssen Biotech, Inc."). The study will be conducted in two parts. Part 1, a dose escalation phase, will establish RP2D of afuresertib when administered with enzalutamide or abiraterone. Part 2, a dose expansion phase, will further evaluate long-term safety of the combinations at the RP2Ds in additional subjects. Dose-finding cohorts will be studied in parallel and will evaluate safety and pharmacokinetic to guide selection of the dose regimens for further evaluation. Part 2 will begin once the RP2Ds have been established in Part 1. Additional doses and/or schedules may be explored if warranted, based upon the pharmacokinetic (PK) and pharmacodynamic (PD) assessments or emerging preclinical evidence. Overall, approximately 60 chemotherapy-naïve subjects with mCRPC and who are receiving either enzalutamide or abiraterone will be enrolled into the study.
GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.
Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Clinically significant ECG abnormalities including second degree (Type II) or third degree atrioventricular block.
History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, stenting, or bypass grafting within the past 6 months prior to enrollment.
Class III or IV heart failure as defined by the New York Heart Association functional classification system Left ventricular ejection fraction (LVEF) below 50% Known cardiac metastases Corrected QT interval of >470 millisecond (msec) (or >480 msec with bundle branch block)
Participants will be receiving enzalutamide at the recommended dose for at least 4 weeks prior to enrolment into this cohort. Afuresertib 125mg and enzalutamide 160 mg will be dosed continuously on a once daily schedule for 28-day intervals.
Drug: Afuresertib · Drug: Enzalutamide
Participants will be receiving enzalutamide at the recommended dose for at least 4 weeks prior to enrolment into this cohort. Afuresertib 150 mg and enzalutamide 160 mg will be dosed continuously on a once daily schedule for 28-day intervals.
Drug: Afuresertib · Drug: Enzalutamide
Participants will be receiving enzalutamide at the recommended dose for at least 4 weeks prior to enrolment into this cohort. Afuresertib 175 mg and enzalutamide 160 mg will be dosed continuously on a once daily schedule for 28-day intervals.
Drug: Afuresertib · Drug: Enzalutamide
Participants will be receiving enzalutamide at the recommended dose for at least 4 weeks prior to enrolment into this cohort. Afuresertib 200 mg and enzalutamide 160 mg will be dosed continuously on a once daily schedule for 28-day intervals.
Drug: Afuresertib · Drug: Enzalutamide
Participants will be receiving abiraterone at the recommended dose for at least 2 weeks prior to enrolment into this cohort. Afuresertib 125mg and abiraterone 1000 mg will be dosed continuously on a once daily schedule for 28-day intervals. Continuous BID prednisone 5mg will be coadministered per the labelled recommendations.
Drug: Afuresertib · Drug: Abiraterone · Drug: Prednisone
Participants will be receiving abiraterone at the recommended dose for at least 2 weeks prior to enrolment into this cohort. Afuresertib 150mg and abiraterone 1000 mg will be dosed continuously on a once daily schedule for 28-day intervals. Continuous BID prednisone 5mg will be coadministered per the labelled recommendations.
Drug: Afuresertib · Drug: Abiraterone · Drug: Prednisone
Participants will be receiving abiraterone at the recommended dose for at least 2 weeks prior to enrolment into this cohort. Afuresertib 100 mg and abiraterone 1000 mg will be dosed continuously on a once daily schedule for 28-day intervals. Continuous BID prednisone 5mg will be coadministered per the labelled recommendations.
Drug: Afuresertib · Drug: Abiraterone · Drug: Prednisone
Participants in this arm will receive RP2D of afuresertib established in escalation cohort in addition to plus enzalutamide 160 mg once daily.
Drug: Afuresertib · Drug: Enzalutamide
Participants in this arm will receive RP2D of afuresertib established in escalation cohort in addition to abiraterone 1000 mg once daily and continuous BID prednisone 5 mg coadministered per the labelled recommendations.
Drug: Afuresertib · Drug: Abiraterone · Drug: Prednisone
Participants in this arm will receive RP2D of afuresertib established in escalation cohort in addition to abiraterone 1000 mg once daily and continuous BID prednisone 5 mg coadministered per the labelled recommendations
Drug: Afuresertib · Drug: Abiraterone · Drug: Prednisone
White of off-white round immediate release tablet for oral administration with unit dose strength of 50 mg and 75 mg to achieve the dosage level of 100 mg, 125 mg, 150 mg or 200 mg once daily.
Opaque white to off-white capsule for oral administration with unit dose strength of 40mg to achieve dose level of 160 mg once daily.
White to off-white tablet for oral administration with unit dose strength 250 mg to achieve dose level of 1000 mg once daily.
Continuous twice daily co administration of prednisone 5 mg as per labelled recommendation from United State Prescribing Information.
Number of participants with adverse events (AEs), serious adverse events (SAEs) and dose limiting toxicities as a safety measure.
All AEs and SAEs will be collected and recorded from receipt of first dose of study drug until 30 days after the last dose of study drug, or until the start of subsequent therapy.
Time frame: From first dose of study drug until 30 days after last dose of study drug (assessed up to average of 6 months).
Change from baseline in composite of laboratory parameters as a safety measure: hematology, clinical chemistry and urinalysis.
Changes in the laboratory parameter including hematology, clinical chemistry and urinalysis will be assessed as a measure of safety tolerability and to establish RP2D.
Time frame: From baseline up to end of treatment (assessed up to average of 6 months).
Change from baseline in electrocardiogram values as a safety measure.
Changes in electrocardiograms (ECGs) values will be assessed as a measure of safety, tolerability and to establish RP2D.
Time frame: From baseline up to average of 6 months.
Change from baseline in composite of vital signs as a safety measure: blood pressure, temperature and pulse rate.
Changes in vital sign values of blood pressure, temperature and pulse rate will be assessed as a measure of safety, tolerability and to establish RP2D.
Time frame: From baseline up to end of treatment (assessed up to average of 6 months).
Composite of PK parameters as a measure of RP2D following administration of afuresertib plus enzalutamide or afuresertib plus abiraterone: AUC and Cmax.
PK parameters of area under time concentration curve (AUC) and maximum plasma concentration (Cmax) will be evaluated to determine RP2D of afuresertib.
Time frame: Pre-dose Sample on Day 1 of Cycle 1, 2, 3, 4, and then every 12 weeks and again on Day 1 of Cycle 7 (assessed up to 169 days).
Composite of PK parameters as a measure of RP2D following administration of afuresertib plus abiraterone: AUC and Cmax.
PK parameters of area under time concentration curve (AUC) and maximum plasma concentration (Cmax) will be evaluated.
Time frame: Pre-dose and 2 hours post dose sample will be collected on Day 8 of Cycle 1.
Number of participants with adverse events, serious adverse events and dose limiting toxicities to establish RP2D of afuresertib.
All AEs and SAEs will be collected and recorded from receipt of first dose of study drug until 30 days after the last dose of study drug, or until the start of subsequent therapy.
Time frame: Cycle 1 (28 days).
Change from baseline in composite of laboratory parameters to establish RP2D of afuresertib: hematology, clinical chemistry and urinalysis.
Changes in the laboratory parameter including hematology, clinical chemistry and urinalysis will be assessed as a measure of safety tolerability and to establish RP2D.
Time frame: From baseline up to 28 days (Cycle 1).
Change from baseline in electrocardiogram values to establish RP2D of afuresertib.
Changes in electrocardiograms (ECGs) will be assessed as a measure of safety, tolerability and to establish RP2D.
Time frame: From baseline up to 28 days (Cycle 1).
Change from baseline composite of vital sign values to establish RP2D of afuresertib: blood pressure, temperature and pulse rate.
Changes in vital sign values of blood pressure, temperature and pulse rate will be assessed as a measure of safety, tolerability and to establish RP2D.
Time frame: From baseline up to 28 days (Cycle 1).
Composite of afuresertib PK parameters following administration with enzalutamide: AUC and Cmax.
PK profile of afuresertib will be established following administration with enzalutamide by assessing AUC and Cmax.
Time frame: Blood samples will be collected at pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post dose on Day 1of Cycle 1.
Composite of enzalutamide PK parameters following administration alone and in combination with afuresertib: AUC and Cmax.
PK profile of enzalutamide will be establish by assessing AUC and Cmax when administered alone and in combination with afuresertib.
Time frame: Blood samples will be collected at pre-dose, 0.5, 1, 2, 3, 4, 6 and 24 hours post dose on Day-1 and Day 1 in Cycle 2.
Composite of PK parameters following administration afuresertib and abiraterone alone and in combination with each other: AUC and Cmax.
PK profile of afuresertib and abiraterone will be establish by assessing AUC and Cmax when administered alone and in combination with each other.
Time frame: Blood samples will be collected at pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post dose on Day 15 of Cycle 1 and Day 1 of Cycle 2 for afuresertib and on Day-1 and Day 1 in Cycle 2 for abiraterone.
No study locations are listed for this record.
This study is withdrawn, as verified in Oct 2016. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
GlaxoSmithKline