Hepatocellular CarcinomaPhase 1/2NCT02828124
A Study of the Safety and Tolerability of BMS-986183 in Patients With Liver Cancer
A Phase 1/2 study testing BMS-986183 and Nivolumab in people with Hepatocellular Carcinoma, run by Bristol-Myers Squibb at 4 sites in 4 countries.
Trial summary
The purpose of this study is to evaluate the safety and tolerability of BMS-986183 in patients with liver cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- BMS-986183 and Nivolumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 4 sitesin 4 countries
- Study dates
- 23 Aug 2016to 8 Jan 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
4 sites in 4 countries.
4 sites in 4 countries
About this study
Official title: 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.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- BMS-986183, Nivolumab
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BMS-986183Biological
specified dose on specified days
NivolumabBiological
Also called BMS-936558, Opdivo
specified dose on specified days
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation Monotherapy | Experimental | Not described Receives: Biological: BMS-986183 |
| Dose Expansion Monotherapy | Experimental | Not described Receives: Biological: BMS-986183 |
| Dose Escalation Combination Therapy | Experimental | Not described Receives: Biological: BMS-986183; Biological: Nivolumab |
| Dose Expansion Combination Therapy | Experimental | Not described Receives: Biological: BMS-986183; Biological: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events at Its Worst Grade
Evaluated by comparing the incidence of Adverse Events (AEs) among subjects using their assigned treatment for at least one day.
Measured: First dose up to approximately 24 months
Incidence of Serious Adverse Events at Its Worst Grade
Evaluated by comparing the incidence of Serious Adverse Events (SAEs) among subjects using their assigned treatment for at least one day.
Measured: First dose up to approximately 24 months
Incidence of Adverse Events Leading to Discontinuation
Evaluated by comparing the incidence of Adverse Events leading to discontinuation among subjects using their assigned treatment for at least one day.
Measured: First dose up to approximately 24 months
Incidence of Adverse Events Leading to Death
Evaluated by comparing the incidence of Adverse Events leading to death among subjects using their assigned treatment for at least one day.
Measured: First dose up to approximately 24 months
Incidence of Laboratory Test Toxicity Grade Shifting From Baseline
Measured: First dose up to approximately 24 months
Secondary outcomes (21)
Best Overall Response (BOR)
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.
Measured: First dose up to approximately 24 months
Overall Response Rate (ORR)
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
Measured: First dose up to approximately 24 months
Duration of Response (DoR)
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
Measured: First dose up to approximately 24 months
Progression Free Survival (PFS)
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.
Measured: First dose up to approximately 24 months
PFS Rate at Week 't'
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
Measured: First dose up to approximately 24 months
Maximum Observed Concentration (Cmax)
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
Measured: From first does up to approximately 24 months
Time of Maximum Observed Concentration (Tmax)
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.
Measured: 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)]
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)]
Measured: First does up to appromimately 24 months
Area Under the Concentration-time Curve in 1 Dosing Interval [AUC(TAU)]
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).
Measured: First dose up to approximately 24 months
Concentration at the End of a Dosing Interval (Ctau)
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
Measured: First dose up to approximately 24 months
Trough Observed Concentration, Including Predose Concentrations and Ctau (Ctrough)
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)
Measured: First dose up to approximately 24 months
Total Body Clearance (CLT)
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
Measured: First dose to approximately 24 months
Apparent Volume of Distribution at Steady-state (Vss)
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
Measured: First dose up to approximately 24 months
Volume of Distribution of Terminal Phase (Vz)
(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.
Measured: First dose up to approximately 24 months
Accumulation Index; Ratio of Cmax at Steady-state to Cmax After the First Dose (AI_Cmax)
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.
Measured: First dose up to approximately 24 months
Accumulation Index; Ratio of Ctau at Steady-state to Ctau After the First Dose (AI_Ctau)
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.
Measured: 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)]
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).
Measured: 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)
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.
Measured: First dose up to approximately 24 months
Terminal Half-life (T-HALF)
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.
Measured: First dose up to approximately 24 months
Changes in QTcF (ΔQTcF) From Baseline
To assess the effect of dosage regimen and exposure [active ADC and unconjugated tubulysin] of BMS-986183 as monotherapy on the QT interval.
Measured: Baseline up to approximately 24 months
Incidence of Positive Anti-drug Antibody (ADA)
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.
Measured: First dose up to approximately 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2016 (estimated)
- Study start23 Aug 2016
- Primary completion8 Jan 2018
- Study completion8 Jan 2018
Why it stopped: Business objectives have changed
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02828124
- Sponsor's protocol ID
- CA015-003
- Status last verified
- Jan 2019
- First submitted
- 7 Jul 2016
- Last updated
- 30 Jan 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Study of BMS-986183 in Subjects With Advanced Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT02828124
- Acronym / sponsor ID
- CA015-003
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business objectives have changed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- 23 Aug 2016 (actual)
- Primary completion
- 8 Jan 2018 (actual)
- Study completion
- 8 Jan 2018 (actual)
- First posted
- 11 Jul 2016 (estimated)
- Results
- Posted 30 Jan 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and tolerability of BMS-986183 in patients with liver cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation Monotherapy | Experimental | Biological: BMS-986183 |
| Dose Expansion Monotherapy | Experimental | Biological: BMS-986183 |
| Dose Escalation Combination Therapy | Experimental | Biological: BMS-986183, Biological: Nivolumab |
| Dose Expansion Combination Therapy | Experimental | Biological: BMS-986183, Biological: Nivolumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BMS-986183specified dose on specified days | Biological | Dose Escalation Combination Therapy, Dose Escalation Monotherapy, Dose Expansion Combination Therapy, Dose Expansion Monotherapy |
| NivolumabAlso: BMS-936558, Opdivospecified dose on specified days | Biological | Dose Escalation Combination Therapy, Dose Expansion Combination Therapy |
Primary outcome
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.
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.
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.
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.
Incidence of Laboratory Test Toxicity Grade Shifting From Baseline
Time frame: First dose up to approximately 24 months
21 secondary outcomes
Best Overall Response (BOR)
Time frame: First dose up to approximately 24 months
Overall Response Rate (ORR)
Time frame: First dose up to approximately 24 months
Duration of Response (DoR)
Time frame: First dose up to approximately 24 months
Progression Free Survival (PFS)
Time frame: First dose up to approximately 24 months
PFS Rate at Week 't'
Time frame: First dose up to approximately 24 months
Maximum Observed Concentration (Cmax)
Time frame: From first does up to approximately 24 months
Time of Maximum Observed Concentration (Tmax)
Time frame: 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
Area Under the Concentration-time Curve in 1 Dosing Interval [AUC(TAU)]
Time frame: 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
Trough Observed Concentration, Including Predose Concentrations and Ctau (Ctrough)
Time frame: First dose up to approximately 24 months
Total Body Clearance (CLT)
Time frame: First dose to approximately 24 months
Apparent Volume of Distribution at Steady-state (Vss)
Time frame: First dose up to approximately 24 months
Volume of Distribution of Terminal Phase (Vz)
Time frame: 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
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
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
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
Terminal Half-life (T-HALF)
Time frame: First dose up to approximately 24 months
Changes in QTcF (ΔQTcF) From Baseline
Time frame: Baseline up to approximately 24 months
Incidence of Positive Anti-drug Antibody (ADA)
Time frame: First dose up to approximately 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
4 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BMS-986183 and Nivolumab in people with Hepatocellular Carcinoma, run by Bristol-Myers Squibb at 4 sites in 4 countries.
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 5 inclusion and 11 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 30 Jan 2019. 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 Canada, Singapore, South Korea, Taiwan. 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 30 Jan 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?
Incidence of Adverse Events at Its Worst Grade (time frame: First dose up to approximately 24 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Jan 2019.