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Advanced Estrogen Receptor Positive HER2- Breast CancerPhase 1/2NCT02983604

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

A Phase 1/2 study testing GS-5829, Exemestane and Fulvestrant in people with Advanced Estrogen Receptor Positive HER2- Breast Cancer, run by Gilead Sciences at 6 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
GS-5829, Exemestane and Fulvestrant
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
6 sitesUnited States
Study dates
10 Jan 2017to 19 Jul 2018
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically confirmed breast cancer with evidence of metastatic or locally advanced disease not amenable to resection or radiation therapy with curative intent and who have progressed during treatment with at least one prior hormonal therapy
  • Phase 1b Dose Escalation - Individuals may have had unlimited prior hormonal therapy and a total of 2 prior chemotherapy regimens (adjuvant chemotherapy is considered 1 regimen). Individuals may have progressed on fulvestrant or exemestane.
  • Randomized Phase 2 Dose Expansion - Individuals may have disease progression during treatment or within 12 months of completion of endocrine therapy (tamoxifen, and/or AI) in the adjuvant setting, or disease progression during treatment with endocrine therapy (tamoxifen, AI or CDK4/6 inhibitor plus AI) for advanced/metastatic disease. Individuals may have had unlimited prior hormonal therapy, but must be naive to fulvestrant in the metastatic setting. A total of 2 prior chemotherapies are allowed, however, only one for metastatic disease is permitted.
  • Documentation of ER positive (≥ 1% positive stained cells by local standards) based on the most recent tumor biopsy, unless bone-only disease
  • Documented HER2-negative tumor based on local testing on most recent tumor biopsy (immunohistochemistry score 0/1+ or negative by in situ hybridization HER2/CP17 ratio < 2 or for single probe assessment HER2 copy number < 4)
  • Post-, pre- or peri-menopausal women considered to be in the post-menopausal state as defined by one of the following:
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  • Age ≥ 60 years
  • Age < 60 years and cessation of regular menses for at least 12 consecutive months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression and serum estradiol and follicle-stimulating hormone (FSH) level within the post-menopausal range
  • Prior bilateral oophorectomy
  • Pre-/peri-menopausal women can be enrolled if amenable to be treated with the luteinizing-hormone releasing hormone (LHRH) agonist, goserelin. Individuals must have commenced treatment with goserelin or an alternative LHRH agonist at least 4 weeks prior to Cycle 1 Day 1 (C1D1). If individuals have received an alternative LHRH agonist prior to study entry, they must switch to goserelin on or before Cycle 1 Day 1 (C1D1) for the duration of the study
  • Measurable disease defined per RECIST v. 1.1, or bone-only disease must have a lytic or mixed lytic blastic lesion that can be accurately assessed by computed tomography (CT) or magnetic resonance imaging (MRI). Individuals with bone-only disease and blastic-only metastases are not eligible
  • All acute toxic effects of any prior antitumor therapy resolved to Grade ≤ 1 before the start of study drug dosing (with the exception of alopecia [Grade 1 or 2 permitted] and neurotoxicity [Grade 1 or 2 permitted])
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
  • Life expectancy of ≥ 3 months, in the opinion of the investigator
  • Adequate organ function defined as follows:
  • Hematologic: Platelets ≥ 100 x 10^9/L; Hemoglobin ≥ 9.0 g/dL; absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (without platelet transfusion or any granulocytic growth factors within previous 7 days of the hematologic laboratory values obtained at screening visit)
  • Hepatic: aspartate transaminase (AST) / alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN) (if liver metastases are present, ≤ 5 x ULN); total or conjugated bilirubin ≤ 1.5 x ULN
  • Renal: Serum Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 60 mL/min as calculated by the Cockroft-Gault method
  • Coagulation: International Normalized Ratio (INR) ≤ 1.2
  • Negative serum pregnancy test
  • Females of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in the study protocol
  • Females who are nursing must agree to discontinue nursing before the first dose of GS-5829
  • Able and willing to provide written informed consent to participate in the study

Who cannot join

  • History or evidence of clinically significant disorder, condition, or disease that, in the opinion of the investigator or the Gilead medical monitor would pose a risk to individual safety or interfere with the study evaluations, procedures, or completion
  • Known brain metastasis or leptomeningeal disease (Note: if treated and stable at least 6 months prior to enrollment, individual is eligible).
  • Uncontrolled intercurrent illness including, but not limited to, active uncontrolled infection, active or chronic bleeding event within 28 days prior to C1D1, uncontrolled cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements as judged by treating physician
  • Myocardial infarction, symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months of C1D1
  • Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (i.e., larger than what is required for placement of central venous access, percutaneous feeding tube) within 28 days of C1D1
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of GS-5829, including any unresolved nausea, vomiting, or diarrhea that is Common Terminology Criteria for Adverse Events (CTCAE) Grade > 1
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  • Minor surgical procedure(s) within 7 days of enrollment or randomization, or not yet recovered from prior surgery (placement of central venous access device, fine needle aspiration, or endoscopic biliary stent ≥ 1 day before enrollment or randomization is acceptable)
  • History of a concurrent or second malignancy, except for: adequately treated local basal cell or squamous cell carcinoma of the skin; cervical carcinoma in situ; superficial bladder cancer; adequately treated Stage 1 or 2 cancer currently in complete remission; any other cancer that has been in complete remission for ≥ 5 years
  • Anti-tumor therapy (chemotherapy, chemoradiation, radiation, antibody therapy, molecular targeted therapy) within 21 days or 5 half-lives whichever is longer, of C1D1 (6 weeks for nitrosoureas, mitomycin C, or molecular agents with t1/2 > 10 days); 5 half-lives of any investigational drug; concurrent use of goserelin for pre-/peri-menopausal breast cancer and exemestane or fulvestrant per the protocol are permitted
  • History of long QT syndrome or whose corrected QT interval (QTc) measured (Fridericia method) at screening is prolonged (> 470 ms). Individuals who screen fail due to this criterion are not eligible to be re-screened
  • Prior exposure to any bromodomain (BET) inhibitors
  • Known hypersensitivity to the study drugs (GS 5829, fulvestrant or exemestane), the metabolites, or formulation excipients
  • Immunotherapy within 6 months of C1D1
  • Evidence of bleeding diathesis or clinically significant bleeding, within 28 days of C1D1 or history of hemoptysis of > 2.5 mL/1 teaspoon within 6 months of C1D1
  • Anticoagulation/antiplatelet therapy within 7 days of C1D1, including acetylsalicylic acid, low molecular weight heparin, or warfarin
  • Known human immunodeficiency virus (HIV) infection
  • Hepatitis B surface Antigen (HBsAg) positive
  • Hepatitis C virus (HCV) antibody positive with HCV RNA positive
  • Use of moderate/strong cytochrome P450 (CYP)3A4 inhibitors or moderate/strong CYP3A4 inducers within 2 weeks prior to C1D1
  • History of high grade esophageal or gastric varices
  • Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Baylor University Medical Center

    Houston, Texas, 77030

  • Allina Health, Virginia Piper Cancer Institute

    Minneapolis, Minnesota, 55407

  • The Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Medical Oncology Associates, PS (dba Summit Cancer Centers)

    Spokane, Washington, 99208

  • Stanford Women's Cancer Center

    Stanford, California, 94305

Other trials in United States

About this study

Official title: 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

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.

Being tested
GS-5829, Exemestane, Fulvestrant
Keywords
Exemestane, Aromasin, Fulvestrant, Faslodex, Breast Cancer, HER 2-, Estrogen receptor positive
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GS-5829Drug

    Tablet(s) administered orally once daily

  • ExemestaneDrug

    Also called Aromasin®

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

  • FulvestrantDrug

    Also called Faslodex®

    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.

Study groups in NCT02983604
Study groupRoleWhat they receive
GS-5829 + exemestane (Phase 1b)ExperimentalParticipants 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.
Receives: Drug: GS-5829; Drug: Exemestane
GS-5829 + fulvestrant (Phase 1b)ExperimentalParticipants 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.
Receives: Drug: GS-5829; Drug: Fulvestrant
GS-5829 + fulvestrant (Phase 2)ExperimentalParticipants will receive GS-5829 (dose determined from Phase 1b) + fulvestrant until disease progression, unacceptable toxicity, withdrawal of consent, or death, whichever comes first.
Receives: Drug: GS-5829; Drug: Fulvestrant
Fulvestrant (Phase 2)Active comparatorParticipants will receive fulvestrant alone until disease progression, unacceptable toxicity, withdrawal of consent, or death, whichever comes first.
Receives: Drug: Fulvestrant

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1b Dose Escalation: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) Through Day 28 at Each Dose Level of GS-5829

    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

    Measured: Baseline up to 28 days

  2. Randomized Phase 2 Dose Expansion: Progression-Free Survival

    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.

    Measured: Baseline up to 2 years

Secondary outcomes (6)

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

    Cmax is defined as the maximum observed concentration of drug.

    Measured: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Days 1 and 15

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

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

    Measured: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Day 15

  3. 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

    Measured: Baseline up to 2 years

  4. Randomized Phase 2 Dose Expansion: Overall Response Rate

    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.

    Measured: Baseline up to 2 years

  5. Randomized Phase 2 Dose Expansion: Clinical Benefit Rate

    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.

    Measured: Baseline up to 2 years

  6. Randomized Phase 2 Dose Expansion: Overall Survival

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

    Measured: Baseline up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Dec 2016 (estimated)
  2. Study start10 Jan 2017
  3. Primary completion19 Jul 2018
  4. Study completion19 Jul 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02983604
Sponsor's protocol ID
GS-US-350-1937
Other IDs
2016-002365-63, 2016
Status last verified
Jul 2019
First submitted
2 Dec 2016
Last updated
7 Aug 2019
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing GS-5829, Exemestane and Fulvestrant in people with Advanced Estrogen Receptor Positive HER2- Breast Cancer, run by Gilead Sciences at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 7 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1b Dose Escalation: Number of Participants Experiencing Dose Limiting Toxicities (DLTs) Through Day 28 at Each Dose Level of GS-5829 (time frame: Baseline up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02983604.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2019.

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