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Advanced Hepatocellular CarcinomaPhase 1NCT02834780

Phase 1 Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of H3B-6527 in Participants With Advanced Hepatocellular Carcinoma

A Phase 1 study testing H3B-6527 in people with Advanced Hepatocellular Carcinoma and Hepatocellular Carcinoma, run by H3 Biomedicine Inc. at 44 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of H3B-6527, and to assess the safety, tolerability and pharmacokinetics of H3B-6527. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
H3B-6527
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
128 participants
Where
44 sitesin 11 countries
Study dates
28 Dec 2016to 23 Feb 2022
Phase
Phase 1
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

  • Participants with hepatocellular carcinoma.
  • Must have had at least one prior standard-of-care therapy, unless contraindicated.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
  • Must be willing to undergo a biopsy up to 8 weeks before administration of H3B-6527 on Cycle 1 Day 1 for part 2 (dose expansion).
  • Adequate bone marrow and organ function.

Who cannot join

  • Uncontrolled significant active infections, except hepatitis B virus (HBV) or hepatitis C virus (HCV).
  • Known human immunodeficiency virus infection.
  • Presence of gastric or esophageal varices requiring active treatment.
  • Previous treatment with a selective FGF19-FGFR4 targeted therapy.
  • Females of childbearing potential, or males who have not had a successful vasectomy, who are unable or unwilling to follow adequate contraceptive measures.
  • Hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption.

Trial locations and contacts

44 sites in 11 countries.

44 sites in 11 countries

United States15 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Northwestern Unversity

    Chicago, Illinois, 60611

  • University of Cincinnati Cancer Institute

    Cincinnati, Ohio, 45219

  • Simmons Comprehensive Cancer Center

    Dallas, Texas, 75390

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Duke University Cancer Center

    Durham, North Carolina, 27710

  • John theurer Cancer Center at Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • USC/Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Hoag Memorial Hospital Presbyterian

    Newport Beach, California, 92663

  • UC Irvine Medical Center

    Orange, California, 92868-3201

  • University of Pennsylsvania - Perelman Cancer Center for Advanced Medicine

    Philadelphia, Pennsylvania, 19104

  • McGuire VA Medical Center

    Richmond, Virginia, 23249

  • UCLA Medical Center

    Santa Monica, California, 90404

  • Georgetown Unversity Lombardi Comprehensive Cancer Center

    Washington D.C., District of Columbia, 20007

Other trials in United States

Spain8 sites

  • Hospital Universitario de Badajoz

    Badajoz, 06080

  • Hospital Universitario Vall d'Hebron

    Barcelona, 8035

  • General Universitario Gregorio Maranon

    Madrid, 28007

  • START Madrid FJD, Hospital Universitario Fundacion Jimenez Diaz

    Madrid, 28040

  • Hospital Universitario HM Sanchinarro

    Madrid, 28050

  • Clínica Universidad de Navarra

    Pamplona, Navarre, 31008

  • Hospital Universitario Marques de Valdecilla

    Santander, Cantabria, 39008

  • Hospital Universitario Virgen del Rocio

    Seville, 41013

Other trials in Spain

Russia5 sites

  • Altay Regional Oncology Center

    Barnaul, Altay, Re, 656045

  • Russian Oncology Research Center n a N N Blokhin

    Moscow, 115478

  • Omsk Regional Oncology Center

    Omsk, 644046

  • Railway Clinical Hospital JSC RZhD

    Saint Petersburg, 195271

  • City Clinical Oncology Dispensary

    Saint Petersburg, 198255

Other trials in Russia

France4 sites

  • Institut Bergonié

    Bordeaux, 33076

  • Centre Oscar Lambret

    Lille, 59000

  • Hôpital Haut-Lévêque - CHU de Bordeaux

    Pessac, 33604

  • Centre Eugène Marquis

    Rennes, 35042

Other trials in France

Italy3 sites

  • IRCCS Istituto Scientifico Romagnolo per lo studio e la cura dei tumori - U.O. di Oncologia Medica

    Meldola, 47014

  • IRCCS Ospedale San Raffaele S.r.l. - PPDS

    Milan, 20132

  • Azienda Ospedaliero Universitaria - Policlinico di Modena

    Modena, 41124

Other trials in Italy

Belgium2 sites

  • Universitair Ziekenhuis Gent

    Ghent, 9000

  • UCL Cliniques universitaires Saint-Luc

    Woluwe-Saint-Lambert, Brussels Capital, 1200

Other trials in Belgium

Canada2 sites

  • Cross Cancer Institute

    Edmonton, Alberta, T6G IZ2

  • Jurvanski Cancer Center

    Hamilton, Ontario, L8V 5C2

Other trials in Canada

Taiwan2 sites

  • Taichung Veterans General Hospital

    Taichung, 40705

  • National Cheng Kung University Hospital

    Tainan, 704

Other trials in Taiwan

Singapore1 site

  • National University Cancer Insitute

    Singapore, 119074

Other trials in Singapore

South Korea1 site

  • Asan Medical Center

    Seoul, 05505

Other trials in South Korea

United Kingdom1 site

  • Sarah Cannon Research Institute UK - SCRI - PPDS

    London, W1G 6AD

Other trials in United Kingdom

About this study

Official title: An Open-Label Multicenter Phase 1 Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of H3B-6527 in Subjects With Advanced Hepatocellular Carcinoma

The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of H3B-6527, and to assess the safety, tolerability and pharmacokinetics of H3B-6527.

Being tested
H3B-6527
Keywords
Advanced Hepatocellular Carcinoma, H3B-6527, Fibroblast growth factor receptor 4 (FGFR4), Fibroblast growth factor 19 (FGF19)
Medical subject headings
Carcinoma, Hepatocellular, Liver Neoplasms

What participants receive

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

  • H3B-6527Drug

    H3B-6527 by mouth once or twice daily at specified doses.

Study groups in NCT02834780
Study groupRoleWhat they receive
H3B-6527 (escalation and expansion)ExperimentalHepatocellular Carcinoma
Receives: Drug: H3B-6527

What is being measured

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

  1. Part 1, Dose Escalation Phase: Number of Participants With Dose-limiting Toxicities (DLTs) Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03

    DLTs were defined as any of the following toxicities: Hematology, gastrointestinal, renal, hepatic or nonhematologic toxicities occurring during Cycle 1 in Dose Escalation Phase only and judged by the investigator as related to study drug. This included any Grade 4: neutropenia that does not resolve to Grade less than or equal to (<=) 2 within 7 days, thrombocytopenia, anemia of any duration, diarrhea and/or vomiting irrespective of prophylaxis or appropriate treatment; Grade 3: thrombocytopenia requiring transfusion, thrombocytopenia and clinically significant bleeding, anemia if transfused or if lasting for more than 7 days, nausea, vomiting and/or diarrhea lasting more than 72 hours despite the use of optimal anti-emetic/antidiarrheal treatment, bilirubin, fatigue lasting less than 1 week, elevations in biochemistry laboratory values without associated clinical symptoms that last for <=7 days; Grade greater than or equal to (>=) 3 serum creatinine.

    Measured: Cycle 1 (Cycle length = 21 days)

  2. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    A TEAE was defined as an adverse event (AE) that emerges during treatment, having been absent at pretreatment (Baseline) or reemerges during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsens in severity during treatment relative to the pretreatment state, when the AE was continuous. An SAE was any untoward medical occurrence that at any dose: Resulted in death, was life-threatening (that is, the participant was at immediate risk of death from the AE as it occurred; this does not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug).

    Measured: From the first dose of study drug up to approximately 36.7 months

  3. Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters

    Laboratory assessment included hematology, coagulation, clinical chemistry, and urinalysis parameters.

    Measured: From baseline up to approximately 36.7 months

  4. Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Parameters

    Measured: From baseline up to approximately 36.7 months

  5. Number of Participants With Clinically Significant Change From Baseline in Vital Sign Parameters

    Measured: From baseline up to approximately 36.7 months

Secondary outcomes (8)

  1. Area Under the Plasma Concentration-time Curve From Time 0 Through the Last Measurable Point (AUC0-t) of H3B-6527

    Measured: Part 1, Cycle 1 Day 1 and Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing); Part 2, Cycle 1 Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing) (Cycle 1 length = 21 days)

  2. Maximum Observed Plasma Concentration (Cmax) of H3B-6527

    Measured: Part 1, Cycle 1 Day 1 and Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing); Part 2, Cycle 1 Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing) (Cycle 1 length = 21 days)

  3. Time of Maximum Observed Plasma Concentration (Tmax) of H3B-6527

    Measured: Part 1, Cycle 1 Day 1 and Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing); Part 2, Cycle 1 Day 8: 0-24 hours post-dose (for QD dosing) and 0-10 hours post-dose (for BID dosing) (Cycle 1 length = 21 days)

  4. Part 2, Dose Expansion Phase: Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1

    ORR was defined as the percentage of participants achieving a best overall confirmed response of partial response (PR) or complete response (CR) (PR + CR), from the first dose date until disease progression/recurrence. Responses (PR or CR) were confirmed no less than 4 weeks after the initial response. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in the short axis to less than 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The tumor assessment was done using number of lesions based on modified RECIST v1.1 for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ.

    Measured: From the first dose date until disease progression/recurrence or up to approximately 36.7 months

  5. Part 2, Dose Expansion Phase: Duration of Response (DOR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1

    DOR was defined as the time from the date of first documented CR or PR based on modified RECIST v1.1 until the first documentation of disease progression (PD) as determined by the investigator or death, whichever comes first. CR was defined as the disappearance of all target lesions and non-target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of long diameter (LD) of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).

    Measured: From the date of first documented CR or PR up to approximately 36.7 months

  6. Part 2, Dose Expansion Phase: Progression-free Survival (PFS) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1

    PFS was defined as the time from the first dose date to the date of the first documentation of PD as determined by the investigator or death (whichever occurs first). PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).

    Measured: From the first dose date to the date of the first documentation of PD as determined by the investigator or death (whichever occurs first) up to approximately 36.7 months

  7. Part 2, Dose Expansion Phase: Overall Survival (OS)

    OS was defined as the time from the first dose date to the date of death. OS was assessed using Kaplan-Meier method. The time of death was censored for participants who were without death information at the time of OS analysis.

    Measured: From the date of first dose of study drug until date of death from any cause (up to approximately 36.7 months)

  8. Part 2, Dose Expansion Phase: Time to Response (TTR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1

    TTR was defined as the time from the first dose date to the date of first documented CR/PR. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in the short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

    Measured: From date of first dose of study drug until CR or PR (up to approximately 36.7 months)

Timeline

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

  1. First posted15 Jul 2016 (estimated)
  2. Study start28 Dec 2016
  3. Primary completion23 Feb 2022
  4. Study completion23 Feb 2022

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
128 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02834780
Sponsor's protocol ID
H3B-6527-G000-101
Other IDs
2016-001915-19, 2016
Status last verified
Jul 2021
First submitted
13 Jul 2016
Last updated
13 Nov 2023
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 study testing H3B-6527 in people with Advanced Hepatocellular Carcinoma and Hepatocellular Carcinoma, run by H3 Biomedicine Inc. at 44 sites in 11 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 6 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: finished, as of the sponsor's last update on 13 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 44 sites in United States, Spain, Russia, France, Italy and 6 more countries. 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 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.

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 13 Nov 2023). 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?

Part 1, Dose Escalation Phase: Number of Participants With Dose-limiting Toxicities (DLTs) Based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 (time frame: Cycle 1 (Cycle length = 21 days)). 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?

On the ClinicalTrials.gov record for NCT02834780.

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 13 Nov 2023.

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