Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Breast Neoplasms

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Fulvestrant

Exemestane

Estrogens

Antineoplastic Agents, Hormonal

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Aromatase Inhibitors

Enzyme Inhibitors

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 0.6 mg to determine the MTD.

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 1.4 mg to determine the MTD.

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 2 mg to determine the MTD.

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 3 mg to determine the MTD.

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 4 mg to determine the MTD.

Participants with advanced solid tumors and lymphomas who have failed or are intolerant to standard therapy or for whom no standard therapy exists, will receive alobresib at a dose of 6 mg to determine the MTD.

Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy exists, will receive alobresib at a dose of 2 mg in combination with exemestane 25 mg.

Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy exists, will receive alobresib at a dose of 2 mg in combination with fulvestrant 500 mg.

Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy exists, will receive alobresib at a dose of 3 mg in combination with fulvestrant 500 mg.

Tablet administered orally once daily on Study Day 1 through Cycle 1 Day 28 of 28 days cycle

Alobresib

Tablets administered orally once daily on Cycle 1 Day 1 of 28 days cycle

Administered intramuscularly on Cycle 1 Day 1 of 28 days cycle and every 28 days

Gilead Study Director

The primary objectives of this study are to characterize the safety and tolerability and determine the maximum tolerated dose (MTD) or recommended dose for phase 2 study (RDP2) of alobresib as a monotherapy in participants with advanced solid tumors and lymphomas, and in combination with exemestane or fulvestrant in participants with advanced estrogen receptor positive breast cancer.

Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Alobresib (Formerly GS-5829) in Adults With Advanced Solid Tumors and Lymphomas and in Combination With Exemestane or Fulvestrant in Adults With Estrogen Receptor Positive Breast Cancer

A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Alobresib (Formerly GS-5829) as a Monotherapy in Subjects With Advanced Solid Tumors and Lymphomas and in Combination With Exemestane or Fulvestrant in Subjects With Estrogen Receptor Positive Breast Cancer

A DLT was a toxicity, considered possibly related to alobresib, and which occurred during DLT assessment window (Day 1 through Cycle 1 Day 28) in each cohort: Grade ≥ 4 neutropenia (absolute neutrophil count \[ANC\] \< 500/mm\^3); Grade ≥3 neutropenia (ANC\< 1000/mm\^3) with fever (a single temperature of \> 38.3°C or a sustained temperature of ≥ 38°C for more than 1 hour \[hr\]); Grade ≥ 3 thrombocytopenia; Grade ≥ 2 bleeding; Grade ≥ 3 non hematologic toxicity, except Grade 3 nausea or emesis with maximum duration of 48 hrs on adequate medical therapy and Grade 3 diarrhea which persists for \< 72 hrs in absence of maximal medical therapy; Grade ≥ 2 non hematologic treatment-emergent adverse event (TEAE) of potential clinical significance; treatment interruption ≥ 7 days due to unresolved toxicity; and any Grade 3 or 4 elevation in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) associated with a Grade 2 elevation in bilirubin that is at least possibly related to alobresib.

Cmax is defined as the maximum concentration of the drug.

Ctau is defined as the observed drug concentration at the end of the dosing interval.

AUC0-24 is defined as the concentration of drug over time from time zero to time 24 hrs.

AUCtau is defined as the concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Tmax is defined as the time (observed time point) of Cmax.

t1/2 is defined as the estimate of the terminal elimination half-life of the drug. Due to short sampling period of the terminal elimination phase in these cohorts t1/2 values should be interpreted with caution.

Gilead Sciences

The Full Analysis Set included all participants who received at least 1 dose of study drug.

Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 0.6 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.

Monotherapy: Alobresib 0.6 mg

Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 1.4 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.

Monotherapy: Alobresib 1.4 mg

Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 2 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.

Monotherapy: Alobresib 2 mg

Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 3 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.

Monotherapy: Alobresib 3 mg

Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 4 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.

Monotherapy: Alobresib 4 mg

Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 6 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle to determine the MTD.

Monotherapy: Alobresib 6 mg

Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy existed, received alobresib tablets at a dose of 2 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle in combination with exemestane 25 mg tablets administered orally once daily on C1D1 of 28 days cycle.

Combination Therapy: Alobresib 2 mg + Exemestane

Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy existed, received alobresib tablets at a dose of 2 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle in combination with fulvestrant 500 mg administered intramuscularly on C1D1 of 28 days cycle and every 28 days (± 3 days).

Combination Therapy: Alobresib 2 mg + Fulvestrant

Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy existed, received alobresib tablets at a dose of 3 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle in combination with fulvestrant 500 mg administered intramuscularly on C1D1 of 28 days cycle and every 28 days (± 3 days).

Combination Therapy: Alobresib 3 mg + Fulvestrant

Total

Age, Categorical

Sex: Female, Male

Ethnicity

Race/Ethnicity, Customized

Race

Gilead Clinical Study Information Center

Number of Participants Experiencing Dose Limiting Toxicities (DLTs)

Cycle 1 Day 1

Cycle 1 Day 8

Participants in the PK Analysis Set (included all enrolled participants who took at least 1 dose of study drug and had at least 1 nonmissing postdose value reported by the PK laboratory) with available data were analyzed.

Pharmacokinetic (PK) Parameter: Cmax of Alobresib

Participants in the PK Analysis Set with available data were analyzed.

PK Parameter: Ctau of Alobresib

PK Parameter: AUC0-24 of Alobresib

PK Parameter: AUCtau of Alobresib

PK Parameter: Tmax of Alobresib

PK Parameter: t1/2 of Alobresib

Participants with advanced solid tumors and lymphomas who had failed or were intolerant to standard therapy, or for whom no standard therapy existed received alobresib tablets at a dose of 0.6 mg orally once daily on Study Day 1 through Cycle 1 Day 28 (C1D28) of 28 days cycle to determine the maximum tolerated dose (MTD).

Participants with advanced stage estrogen receptor positive breast cancer for whom no standard curative therapy existed, received alobresib tablets at a dose of 2 mg orally once daily on Study Day 1 through C1D28 of 28 days cycle in combination with exemestane 25 mg tablets administered orally once daily on Cycle 1 Day 1 (C1D1) of 28 days cycle.

Overall Study

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Participants who have progressed on either abiraterone and/or enzalutamide will be enrolled to receive increasing doses of alobresib up to 9 mg to determine the MTD.

Following a two week lead-in with enzalutamide once daily, participants who have progressed on abiraterone will receive less than or equal to MTD of alobresib in combination with enzalutamide 160 mg once daily. Based on observed pharmacokinetics (PK) interaction, toxicity, and tolerability observed in the single agent dose escalation, the dose of alobresib may be increased.

Participants will receive a dose less than or equal to MTD of alobresib (based on safety, pharmacodynamics (PD), and tolerability).

Participants will receive a dose less than or equal to MTD of alobresib plus enzalutamide (based on safety, PD, and tolerability).

Participants will receive alobresib plus enzalutamide (dose will be equivalent to the dose chosen for Group 2).

Enzalutamide

This study consists of two phases: Dose Escalation (Phase 1b) and Dose Expansion (Phase 2)

The Dose Escalation phase will characterize the safety, tolerability, and determine the maximum tolerated dose (MTD) of alobresib as a single agent and in combination with enzalutamide, in participants with metastatic castrate-resistant prostate cancer (mCRPC).

The Dose Expansion phase will evaluate the following:

* In group 1, the efficacy of alobresib as a single agent in participants with mCRPC who have progressed while receiving enzalutamide (may have also received abiraterone)
* In group 2, the efficacy of alobresib combined with enzalutamide in participants with mCRPC who have progressed while receiving treatment with abiraterone (may not have previously received enzalutamide)
* In group 3, the efficacy of alobresib combined with enzalutamide in participants with mCRPC who have had prostate specific antigen (PSA) progression, but not radiographic progression, while receiving treatment with enzalutamide (participants may have also previously received abiraterone)

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GS-5829 (Alobresib) as a Single Agent and In Combination With Enzalutamide in Participants With Metastatic Castrate-Resistant Prostate Cancer

A Phase 1b/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GS-5829 as a Single Agent and In Combination With Enzalutamide in Subjects With Metastatic Castrate-Resistant Prostate Cancer

A DLT was a toxicity, considered possibly related to alobresib, and which occurred during the DLT assessment window (Days 1 through 28) in each cohort: Grade ≥ 4 neutropenia (absolute neutrophil count (ANC) \< 500/mm\^3), Grade ≥ 3 neutropenia (ANC\< 1000/mm\^3) with fever (a single temperature \> 38.3°C or a sustained temperature of ≥ 38°C for more than 1 hour (h)), Grade ≥ 3 thrombocytopenia, Grade ≥ 2 bleeding (eg, gastrointestinal, respiratory, epistaxis, purpura), Grade ≥ 3 non hematologic toxicity, except- Grade 3 nausea or emesis with maximum duration of 48 h on adequate medical therapy and Grade 3 diarrhea which persists for \< 72 h in the absence of maximal medical therapy, Grade ≥ 2 non hematologic treatment emergent adverse event (TEAE) that in the opinion of the investigator was of potential clinical significance such that further dose escalation would expose participants to unacceptable risk, treatment interruption ≥ 7 days due to unresolved toxicity.

The non-progression rate at Week 24 was defined as the proportion of participants who did not progress by Week 24.

Cmax is the maximum observed concentration of drug in plasma.

Ctau is the observed concentration of drug in plasma at the end of dosing.

AUClast is the concentration of drug over time zero to last concentration (area under the plasma concentration versus time curve).

Tmax is the time observed for the Cmax of alobresib.

PSA response was defined as percentage of participants with ≥ 30% decline in PSA from baseline by 12 weeks.

PFS was defined as the interval from first dose date of study drug to the earlier of the first documentation of definitive disease progression (assessed per PCWG2) or death from any cause. PCWG2 criteria for progression was determined as 'Decline from baseline' when record start of therapy to first prostate-specific antigen (PSA) increase that is ≥ 25% and ≥ 2 ng/mL above the nadir and confirmed by a second value 3 or more weeks later; 'No decline from baseline' when PSA progression ≥ 25% and ≥ 2 ng/mL after 12 weeks.

OS is defined as the interval from first dose date of study drug to death from any cause.

The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.

Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the maximum tolerated dose (MTD).

Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.

Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.

Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.

Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.

Monotherapy: Alobresib 9 mg

Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.

Combination Therapy: Alobresib 3 mg + Enzalutamide

Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.

Combination Therapy: Alobresib 6 mg + Enzalutamide

Age, Continuous

Ethnicity (NIH/OMB)

United States

Region of Enrollment

All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.

The DLT Analysis Set included all participants in the Safety Analysis Set who completed all treatment and safety procedures through Day 28, inclusive, or experienced a DLT prior to Day 28, exclusive.

Phase 1b Dose Escalation: Number of Participants Experienced Dose Limiting Toxicities (DLTs)

Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the MTD.

The Phase 2 Dose Expansion of the study was not conducted.

Phase 2 Dose Expansion: Non-progression Rate at Week 24 According to Prostate Cancer Working Group (PCWG2) Criteria

Cycle 1 Day 15

Cycle 2 Day 1

The PK Analysis Set included participants who took at least 1 dose of study drug and have at least 1 non-missing postdose concentration value. Participants with available data were analyzed.

Monotherapy: Samples were not collected at Cycle 1 Day 1 and Cycle 1 Day 15; samples were only collected for participants who received alobresib 3 mg, 6 mg and 9 mg doses at Cycle 2 Day 1. Combination Therapy: Samples were not collected at Cycle 1 Day 8 and Cycle 2 Day 1.

Phase 1b Dose Escalation: Cmax: Maximum Observed Plasma Concentration of Alobresib

Participants in the PK Analysis Set with available data were analyzed.

Monotherapy: Samples were not collected at Cycle 1 Day 15; samples were only collected for participants who received alobresib 3 mg, 6 mg and 9 mg doses at Cycle 2 Day 1. Combination Therapy: Samples were not collected at Cycle 1 Day 8 and Cycle 2 Day 1.

Phase 1b Dose Escalation: Ctau: Observed Drug Concentration at the End of the Dosing Interval of Alobresib

Participants in the PK Analysis Set with available data were analyzed.

Monotherapy: Samples were not collected at Cycle 1 Day 1 and Cycle 1 Day 15; samples were only collected for participants who received alobresib 3 mg, 6 mg and 9 mg doses at Cycle 2 Day 1. Combination Therapy: Samples were not collected at Cycle 1 Day 8 and Cycle 2 Day 1.

Phase 1b Dose Escalation: AUClast: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration of Alobresib

Phase 1b Dose Escalation: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of Alobresib

Phase 1b Dose Escalation: Tmax: Time (Observed Time Point) of Cmax of Alobresib

Participants in the Full Analysis Set were analyzed.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Alobresib (Formerly GS-5829) in Adults With Advanced Solid Tumors and Lymphomas and in Combination With Exemestane or Fulvestrant in Adults With Estrogen Receptor Positive Breast Cancer	NCT02392611	Solid Tumors an...	Alobresib Exemestane Fulvestrant	18 Years -	Gilead Sciences
Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Alobresib (Formerly GS-5829) in Adults With Advanced Solid Tumors and Lymphomas and in Combination With Exemestane or Fulvestrant in Adults With Estrogen Receptor Positive Breast Cancer	NCT02392611	Solid Tumors an...	Alobresib Exemestane Fulvestrant	18 Years -	Gilead Sciences
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GS-5829 (Alobresib) as a Single Agent and In Combination With Enzalutamide in Participants With Metastatic Castrate-Resistant Prostate Cancer	NCT02607228	Metastatic Cast...	Alobresib Enzalutamide	18 Years -	Gilead Sciences

Spots Global Cancer Trial Database for alobresib

Every month we try and update this database with for alobresib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for alobresib

Every month we try and update this database with for alobresib cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for alobresib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.