Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

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 will be sequentially enrolled at progressively higher dose levels of GS-5829 (up to 9 mg) in combination with exemestane and may continue with treatment until disease progression, unacceptable toxicity, withdrawal of consent, or death, whichever comes first.

Participants will be sequentially enrolled at progressively higher dose levels of GS-5829 (up to 9 mg) in combination with fulvestrant and may continue with treatment until disease progression, unacceptable toxicity, withdrawal of consent, or death, whichever comes first.

Participants will receive GS-5829 (dose determined from Phase 1b) + fulvestrant until disease progression, unacceptable toxicity, withdrawal of consent, or death, whichever comes first.

Participants will receive fulvestrant alone until disease progression, unacceptable toxicity, withdrawal of consent, or death, whichever comes first.

GS-5829

25 mg tablet administered orally once daily (or in accordance with locally approved labeling)

Administered every 28 days (± 3 days) intramuscularly in accordance with locally approved labeling

Participants initiating fulvestrant on Cycle 1 Day 1 and have not received any prior dose of fulvestrant will receive a single additional dose of fulvestrant on Cycle 1 Day 15.

Gilead Study Director

The primary objectives of the Phase 1b Dose Escalation part of this study are to characterize the safety and tolerability of GS-5829 in combination with exemestane or fulvestrant and to determine the maximum tolerated dose (MTD) or the recommended Phase 2 dose of GS-5829 in combination with fulvestrant in women with advanced estrogen receptor positive, HER2-negative (ER+/HER2-) breast cancer.

The primary objective of the Randomized Phase 2 Dose Expansion portion of this study is to evaluate the efficacy of GS-5829 in combination with fulvestrant compared to fulvestrant alone in women with advanced ER+/HER2- breast cancer.

This study was terminated early and the Phase 2 portion of the study was not conducted.

GS-5829 in Combination With Fulvestrant or Exemestane in Women With Advanced Estrogen Receptor Positive, HER2 Negative-Breast Cancer

A Phase 1b/2 Study of GS-5829 in Combination With Fulvestrant or Exemestane in Subjects With Advanced Estrogen Receptor Positive, HER2 Negative-Breast Cancer

A DLT was a toxicity as defined below:

* Grade ≥ 4 neutropenia
* Grade ≥ 3 neutropenia with fever
* Grade ≥ 3 thrombocytopenia
* Grade ≥ 2 bleeding (e.g., gastrointestinal, respiratory, epistaxis, purpura)
* Grade ≥ 3 or higher non-hematologic toxicity, except:

  * Grade 3 nausea or emesis with maximum duration of 48 hours on adequate medical therapy
  * Grade 3 diarrhea which persists for \< 72 hours in the absence of adequate medical therapy
* Grade ≥ 2 non-hematologic treatment-emergent adverse event (TEAE) that in the opinion of the investigator is of potential clinical significance such that further dose escalation would expose participants to unacceptable risk
* Treatment interruption of ≥ 7 days due to unresolved toxicity
* Grade 3 or Grade 4 elevation in aspartate transaminase (AST) or alanine transaminase (ALT) associated with a Grade 2 elevation in bilirubin that is at least possibly related to study drug

Progression-Free Survival (PFS) was defined as the interval from date of randomization to the earlier of the first documented confirmed disease progression or death from any cause.

Cmax is defined as the maximum observed concentration of drug.

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

Overall response rate (ORR) was defined as the proportion of participants who achieve complete response (CR) or partial response (PR), based on Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 study progression criteria.

Clinical benefit rate (CBR) was defined as the proportion of participants who achieve CR, PR, or stable disease that lasts for \> 24 weeks based on RECIST v. 1.1 study progression criteria.

Overall survival was defined as the interval from date of randomization to date of death from any cause.

Gilead Sciences

Safety Analysis Set included all participants who were enrolled and received at least 1 dose of any study drug.

GS-5829 4 mg tablets once daily + exemestane 25 mg tablet once daily

GS-5829 4 mg + Exemestane

GS-5829 4 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)

GS-5829 4 mg + Fulvestrant

GS-5829 6 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)

GS-5829 6 mg + Fulvestrant

GS-5829 9 mg tablets once daily + fulvestrant 500 mg administered intramuscularly every 28 days (± 3 days)

GS-5829 9 mg + Fulvestrant

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

Gilead Clinical Study Information Center

GS-5829 4 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)

GS-5829 6 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)

GS-5829 9 mg tablets once daily + fulvestrant 500 mg administered intramuscularly on Days 1, 15, and 29, and then every 28 days (or in accordance with locally approved labeling)

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 Experiencing Dose Limiting Toxicities (DLTs) Through Day 28 at Each Dose Level of GS-5829

As the study was terminated prior to the Phase 2 portion of the study, no participants were enrolled in the Phase 2 portion of the study and data was not collected for this endpoint.

Randomized Phase 2 Dose Expansion: Progression-Free Survival

Day 1

Day 15

The PK Analysis Set included all enrolled participants who received at least 1 dose of study drug and have at least 1 nonmissing postdose concentration value reported by the PK laboratory, excluding participants who received concomitant medications prohibited in this study. Only participants with available data were analyzed.

Phase 1b Dose Escalation: Pharmacokinetic (PK) Parameter: Cmax of GS-5829

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

Phase 1b Dose Escalation: PK Parameter: AUCtau of GS-5829

Randomized Phase 2 Dose Expansion: Overall Safety Profile as Assessed by the Percentage of Participants Experiencing Any Adverse Events (AEs), Grade 3 or 4 AEs, Treatment-Related AEs, or Abnormalities in Laboratory Tests or Electrocardiograms

Spots Global Cancer Trial Database for GS-5829 in Combination With Fulvestrant or Exemestane in Women With Advanced Estrogen Receptor Positive, HER2 Negative-Breast Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

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