A Study of the Safety and Tolerability of BMS-986183 in Patients With Liver Cancer

January 7, 2019 updated by: Bristol-Myers Squibb

A Phase 1/2 Study of BMS-986183 in Subjects With Advanced Hepatocellular Carcinoma

The purpose of this study is to evaluate the safety and tolerability of BMS-986183 in patients with liver cancer.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
25

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • Local Institution
  • Korea, Republic of
      • Seoul, Korea, Republic of, 05505
        • Local Institution
  • Singapore
      • Singapore, Singapore, 169610
        • Local Institution
  • Taiwan
      • Taipei, Taiwan, 10048
        • Local Institution

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

  • Must have advanced liver cancer that cannot be treated with surgery or other local methods
  • Liver cancer is confirmed by a microscopic examination of tissue
  • Liver disease is classified as 'A' by a standard method called Child-Pugh score
  • Daily living abilities are classified as '0 or 1' by a standard method from the Eastern Cooperative Oncology Group (ECOG)
  • Women must use contraception

Exclusion Criteria:

  • Prior liver transplant
  • Increase in blood pressure in some of the veins entering the liver
  • Cancer that has spread to the brain or the layers of tissue that cover the brain or spinal cord
  • Infection with both hepatitis B and C, both hepatitis D and B, infection with HIV, or other infections
  • Disease of the heart or blood vessels around the heart
  • Active cancers within the last 2 years
  • No more than 2 prior systemic treatments or other investigational agents except PD-1/PD-L1 or Ipilimumab (Part 2)
  • Currently on anti-platelet or anti-coagulation therapy
  • Radiotherapy within 4 weeks of treatment
  • Any major allergies

Other protocol defined inclusion/exclusion criteria could apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Dose Escalation Monotherapy
Biological: BMS-986183
specified dose on specified days
EXPERIMENTAL: Dose Expansion Monotherapy
Biological: BMS-986183
specified dose on specified days
EXPERIMENTAL: Dose Escalation Combination Therapy
Biological: Nivolumab
specified dose on specified days
Other Names:
  • BMS-936558
  • Opdivo
Biological: BMS-986183
specified dose on specified days
EXPERIMENTAL: Dose Expansion Combination Therapy
Biological: Nivolumab
specified dose on specified days
Other Names:
  • BMS-936558
  • Opdivo
Biological: BMS-986183
specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Incidence of Adverse Events at Its Worst Grade
Time Frame: First dose up to approximately 24 months
Evaluated by comparing the incidence of Adverse Events (AEs) among subjects using their assigned treatment for at least one day.
First dose up to approximately 24 months
Incidence of Serious Adverse Events at Its Worst Grade
Time Frame: First dose up to approximately 24 months
Evaluated by comparing the incidence of Serious Adverse Events (SAEs) among subjects using their assigned treatment for at least one day.
First dose up to approximately 24 months
Incidence of Adverse Events Leading to Discontinuation
Time Frame: First dose up to approximately 24 months
Evaluated by comparing the incidence of Adverse Events leading to discontinuation among subjects using their assigned treatment for at least one day.
First dose up to approximately 24 months
Incidence of Adverse Events Leading to Death
Time Frame: First dose up to approximately 24 months
Evaluated by comparing the incidence of Adverse Events leading to death among subjects using their assigned treatment for at least one day.
First dose up to approximately 24 months
Incidence of Laboratory Test Toxicity Grade Shifting From Baseline
Time Frame: First dose up to approximately 24 months
First dose up to approximately 24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Best Overall Response (BOR)
Time Frame: First dose up to approximately 24 months
Defined as BOR designation over the study as a whole, recorded between the dates of first dose until the last tumor assessment prior to subsequent therapy. CR or PR determinations included in the BOR assessment must be confirmed by a second scan performed no less than 4 weeks after the criteria for response are first met.
First dose up to approximately 24 months
Overall Response Rate (ORR)
Time Frame: First dose up to approximately 24 months
Defined as the total number of subjects whose BOR is either a CR or PR divided by the total number of subjects in the population of interest
First dose up to approximately 24 months
Duration of Response (DoR)
Time Frame: First dose up to approximately 24 months
Defined as the time between the date of first response and the subsequent date of objectively documented disease progression or death, whichever occurs first. For those subjects who remain alive and have not progressed or received subsequent therapy, DoR will be censored on the date of last tumor assessment
First dose up to approximately 24 months
Progression Free Survival (PFS)
Time Frame: First dose up to approximately 24 months
Defined as the time from the first dose of study drug to the date of the first objective documentation of tumor progression or death due to any cause. Subjects who did not progress nor died will be censored on the date of their last tumor assessment. Subjects who did not have any on-study tumor assessments will be censored on the date of the first dose of study drug.
First dose up to approximately 24 months
PFS Rate at Week 't'
Time Frame: First dose up to approximately 24 months
Defined as the proportion of subjects who remain progression free and surviving at 't' weeks (t=12, 24, 36, etc). The proportion will be calculated by the product-limit method (Kaplan-Meier [K-M] estimate) which takes into account censored data
First dose up to approximately 24 months
Maximum Observed Concentration (Cmax)
Time Frame: From first does up to approximately 24 months
To characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by Cmax
From first does up to approximately 24 months
Time of Maximum Observed Concentration (Tmax)
Time Frame: First dose up to approximately 24 months
to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by Tmax.
First dose up to approximately 24 months
Area Under the Concentration-time Curve From Time 0 to T of the Last Quantifiable Concentration [AUC(0-T)]
Time Frame: First does up to appromimately 24 months
to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by AUC(0-T)]
First does up to appromimately 24 months
Area Under the Concentration-time Curve in 1 Dosing Interval [AUC(TAU)]
Time Frame: First dose up to approximately 24 months
To characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by AUC(TAU).
First dose up to approximately 24 months
Concentration at the End of a Dosing Interval (Ctau)
Time Frame: First dose up to approximately 24 months
To characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by
First dose up to approximately 24 months
Trough Observed Concentration, Including Predose Concentrations and Ctau (Ctrough)
Time Frame: First dose up to approximately 24 months
to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by (Ctrough)
First dose up to approximately 24 months
Total Body Clearance (CLT)
Time Frame: First dose to approximately 24 months
to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by CLT
First dose to approximately 24 months
Apparent Volume of Distribution at Steady-state (Vss)
Time Frame: First dose up to approximately 24 months
to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by Vss
First dose up to approximately 24 months
Volume of Distribution of Terminal Phase (Vz)
Time Frame: First dose up to approximately 24 months
(to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by Vz.
First dose up to approximately 24 months
Accumulation Index; Ratio of Cmax at Steady-state to Cmax After the First Dose (AI_Cmax)
Time Frame: First dose up to approximately 24 months
to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by AI_Cmax.
First dose up to approximately 24 months
Accumulation Index; Ratio of Ctau at Steady-state to Ctau After the First Dose (AI_Ctau)
Time Frame: First dose up to approximately 24 months
to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by AI_Ctau.
First dose up to approximately 24 months
Accumulation Index; Ratio of AUC(TAU) at Steady-state to AUC(TAU) After the First Dose [AI_AUC(TAU)]
Time Frame: First dose up to approximately 24 months
To characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by AI_AUC(TAU).
First dose up to approximately 24 months
Average Concentration Over a Dosing Interval Calculated by Dividing AUC(TAU) at Steady State by Tau (Css,Ave)
Time Frame: First dose up to approximately 24 months
To characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by Css,avg.
First dose up to approximately 24 months
Terminal Half-life (T-HALF)
Time Frame: First dose up to approximately 24 months
to characterize the PK of the total antibody [unconjugated antibody + antibody conjugated to tubulysin or antibody conjugated to any tubulysin metabolites], active ADC [antibody conjugated to tubulysin], and unconjugated tubulysin) of BMS-986183 as monotherapy and in combination with nivolumab will be measured by T-HALF.
First dose up to approximately 24 months
Changes in QTcF (ΔQTcF) From Baseline
Time Frame: Baseline up to approximately 24 months
To assess the effect of dosage regimen and exposure [active ADC and unconjugated tubulysin] of BMS-986183 as monotherapy on the QT interval.
Baseline up to approximately 24 months
Incidence of Positive Anti-drug Antibody (ADA)
Time Frame: First dose up to approximately 24 months
The immunogenicity of BMS-986183 (as monotherapy and in combination with nivolumab) will be measured by assessment of the presence or absence of specific ADA to BMS-986183. The incidence of positive ADA will be calculated.
First dose up to approximately 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Bristol-Myers Squibb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 23, 2016

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 8, 2018

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 8, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 7, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 8, 2016

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 11, 2016

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 30, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 7, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CA015-003

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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