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.

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Interventions

Study Description

Keywords

Eligibility

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Contact Details

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