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Metastatic Castrate-Resistant Prostate CancerPhase 1/2NCT02607228

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 1/2 study testing Alobresib and Enzalutamide in people with Metastatic Castrate-Resistant Prostate Cancer, run by Gilead Sciences at 4 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

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… Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Alobresib and Enzalutamide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
4 sitesUnited States
Study dates
8 Dec 2015to 3 Sep 2019
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
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically confirmed prostate cancer (individuals with primary neuroendocrine carcinoma of prostate are excluded)
  • Must have documented progressive disease by meeting at least one of the Prostate Cancer Working Group 2 Criteria
  • Castration resistant disease defined as ongoing androgen deprivation therapy with gonadotropin-releasing hormone (GnRH) analogue or bilateral orchiectomy and serum testosterone level ≤ 1.73 nmol/l (50 ng/dL) at screening visit. Individuals who have not had a bilateral orchiectomy must have a plan to maintain effective GnRH-analogue therapy for the duration of the trial.
  • Metastatic disease documented by bone lesions on bone scan or by measurable soft tissue disease by computerized tomography/magnetic resonance imaging (CT/MRI). Patients whose disease spread is limited to regional pelvic lymph nodes are not eligible
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
  • Adequate organ function defined as follows:
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  • 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 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

Who cannot join

  • Known brain metastasis or leptomeningeal disease
  • 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 Cycle 1 Day 1
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of alobresib, including any unresolved nausea, vomiting, or diarrhea that is Common Terminology Criteria for Adverse Events (CTCAE) Grade > 1
  • Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy) within 21 days or 5 half-lives, whichever is longer, of study drug dosing (6 weeks for nitrosoureas, mitomycin C, or molecular agents with t1/2 > 10 days); concurrent use of an luteinizing hormone releasing hormone (LHRH) agonist is permitted for all individuals and ongoing enzalutamide is required in Group 3.
  • History of long QT syndrome or whose corrected QT interval (QTc) measured (Fridericia method) at screening is prolonged (> 450 ms).
  • Prior exposure to bromodomain (BET) inhibitors
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  • Clinically significant bleeding within 28 days of Cycle 1 Day 1
  • Known human immunodeficiency virus (HIV) infection
  • Hepatitis B surface antigen (HBsAg) positive
  • Hepatitis C virus (HCV) antibody positive
  • Use of moderate/strong cytochrome P450 (CYP)3A4 inhibitors or moderate/strong CYP3A4 inducers within 2 weeks prior to the first dose of study drug (with the exception of enzalutamide in the combination arms)
  • Evidence of bleeding diathesis
  • History of hemoptysis of ≥ 2.5 mL/1 teaspoon within 6 months of Cycle 1 Day 1
  • History of high grade esophageal or gastric varices
  • Anticoagulation/antiplatelet therapy within 7 days of Cycle 1 Day 1, including low molecular weight heparin, or warfarin.
  • NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Study site

    Baltimore, Maryland, 21231

  • Study site

    Boston, Massachusetts, 02114

  • Study site

    Durham, North Carolina, 27710

  • Study site

    San Francisco, California, 94158

Other trials in United States

About this study

Official title: 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

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).

Read more

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)
Being tested
Alobresib, Enzalutamide

What participants receive

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

  • AlobresibDrug

    Also called GS-5829

    Tablet administered orally once daily.

  • EnzalutamideDrug

    Also called XTANDI®

    Capsules administered orally once daily.

Study groups in NCT02607228
Study groupRoleWhat they receive
Alobresib Dose EscalationExperimentalParticipants 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.
Receives: Drug: Alobresib
Alobresib + Enzalutamide Dose EscalationExperimentalFollowing 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.
Receives: Drug: Alobresib; Drug: Enzalutamide
Alobresib Dose Expansion (Group 1)ExperimentalParticipants will receive a dose less than or equal to MTD of alobresib (based on safety, pharmacodynamics (PD), and tolerability).
Receives: Drug: Alobresib
Alobresib + Enzalutamide Dose Expansion (Group 2)ExperimentalParticipants will receive a dose less than or equal to MTD of alobresib plus enzalutamide (based on safety, PD, and tolerability).
Receives: Drug: Alobresib; Drug: Enzalutamide
Alobresib + Enzalutamide Dose Expansion (Group 3)ExperimentalParticipants will receive alobresib plus enzalutamide (dose will be equivalent to the dose chosen for Group 2).
Receives: Drug: Alobresib; Drug: Enzalutamide

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 Experienced Dose Limiting Toxicities (DLTs)

    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.

    Measured: Day 1 through Day 28

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

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

    Measured: Week 24

Secondary outcomes (8)

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

    Cmax is the maximum observed concentration of drug in plasma.

    Measured: Monotherapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 8 and Cycle 2 Day 1; Combination therapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Days 1 and 15

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

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

    Measured: Monotherapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 8 and Cycle 2 Day 1; Combination therapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 15

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

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

    Measured: Monotherapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 8 and Cycle 2 Day 1; Combination therapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Days 1 and 15

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

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

    Measured: Monotherapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 8 and Cycle 2 Day 1; Combination therapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 15

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

    Tmax is the time observed for the Cmax of alobresib.

    Measured: Monotherapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 8 and Cycle 2 Day 1; Combination therapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Days 1 and 15

  6. Percentage of Participants Who Had ≥ 30% Reduction in Prostate Specific Antigen (PSA) From Baseline at Week 12

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

    Measured: Baseline; Week 12

  7. Progression Free Survival (PFS)

    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.

    Measured: Up to approximately 4 years

  8. Overall Survival (OS)

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

    Measured: Up to approximately 4 years

Timeline

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

  1. First posted17 Nov 2015 (estimated)
  2. Study start8 Dec 2015
  3. Primary completion25 Oct 2017
  4. Study completion3 Sep 2019

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
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02607228
Sponsor's protocol ID
GS-US-350-1604
Other IDs
2015-003741-26, 2015
Status last verified
Dec 2020
First submitted
16 Nov 2015
Last updated
8 Dec 2020
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Alobresib and Enzalutamide in people with Metastatic Castrate-Resistant Prostate Cancer, run by Gilead Sciences at 4 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 10 inclusion and 16 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 8 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 8 Dec 2020). 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 Experienced Dose Limiting Toxicities (DLTs) (time frame: Day 1 through Day 28). 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 NCT02607228.

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 8 Dec 2020.

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