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AzTrials

Carcinoma, HepatocellularPhase 1NCT03347292

Regorafenib Plus Pembrolizumab in First Line Systemic Treatment of HCC

A Phase 1 study testing Regorafenib(Stivarga, BAY73-4506) and Pembrolizumab in people with Carcinoma, Hepatocellular, run by Bayer at 7 sites in 2 countries.

Completed

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

Official record
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Trial summary

This study will determine if the combination of regorafenib and pembrolizumab is safe and tolerated in patients with advanced liver cancer. In addition, the study will explore the anti-tumor activity of this combination as well as potentially identifying blood and tissue biomarkers associated with disease activity… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Hepatocellular
What is being tested?
Regorafenib(Stivarga, BAY73-4506) and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
7 sitesin 2 countries
Study dates
18 Jun 2018to 6 Sep 2022
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Male or female patients ≥ 18 years of age on day of signing informed consent.
  • Histological or cytological confirmation of HCC (hepatocellular carcinoma) or non-invasive diagnosis of HCC as per American Association for the Study of Liver Diseases (AASLD) criteria in patients with a confirmed diagnosis of cirrhosis.
  • Barcelona Clinic Liver Cancer (BCLC) stage B or C that cannot benefit from treatments of established efficacy such as resection, local ablation, chemoembolization.
  • Liver function status Child-Pugh (CP) Class A. CP status should be calculated based on clinical findings and laboratory results during the screening period.
  • Any local or loco-regional therapy of intrahepatic tumor lesions (e.g. surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed ≥ 4 weeks before first dose of study medication. Note: patients who received sole intrahepatic intra-arterial chemotherapy, without lipiodol or embolizing agents are not eligible.
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
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  • At least one uni-dimensional measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to RECIST (RECIST version 1.1) and no older than 28 days before start of the study treatment. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, may be considered measurable if there has been demonstrated progression in the lesion.
  • Life expectancy of at least 3 months.
  • Adequate bone marrow and organ function as assessed by the laboratory tests performed within 7 days before of treatment initiation.
  • For patients recruited in the expansion cohort only, provision of archival (block) or fresh tumor tissue samples at baseline is mandatory. If archival tumor tissue is not available, patients should be willing to undergo a biopsy for provision of fresh tumor samples

Who cannot join

  • Prior systemic therapy for HCC; prior exposure to regorafenib.
  • Previous treatment with a programmed death 1 (PD1), programmed death-ligand (PD-L1), or cytotoxicT-lymphocyte-associated protein 4 (CTLA-4) inhibitors, or any form of immunotherapy for HCC.
  • Previous treatment with live vaccine within 30 days of planned start of study drugs (seasonal flu vaccines that do not contain a live virus are permitted).
  • Active autoimmune disease (active defined as having autoimmune disease related symptoms and detectable autoantibodies) that has required systemic treatment in the past 2 years (i.e., with use of diseasemodifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drugs. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
  • Known history of human immunodeficiency virus (HIV) infection (HIV 1/2 antibodies).
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  • Dual active HBV infection (HBsAg (+) and /or detectable HBV DNA) and HCV infection (anti-HCV Ab(+) and detectable HCV RNA) at study entry.
  • Pleural effusion or ascites that causes respiratory compromise (≥ CTCAE Grade 2 dyspnea).
  • Known history of metastatic brain or meningeal tumors.
  • Significant acute gastrointestinal disorders with diarrhea as a major symptom e.g., Crohn's disease,malabsorption, or CTCAE Grade ≥ 2 diarrhea of any etiology.

Trial locations and contacts

7 sites in 2 countries.

7 sites in 2 countries

United States5 sites

  • University of Florida Health Sciences Center

    Gainesville, Florida, 32608

  • USC Norris Hospital and Clinics

    Los Angeles, California, 90033

  • Mount Sinai Medical Center

    New York, New York, 10029

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109-1023

  • H. Lee Moffitt Cancer Center & Research Institute

    Tampa, Florida, 33612

Other trials in United States

Germany2 sites

  • Universitätsklinikum Köln

    Cologne, North Rhine-Westphalia, 50937

  • Universitätsmedizin der Johannes Gutenberg Universität Mainz

    Mainz, Rhineland-Palatinate, 55131

Other trials in Germany

About this study

Official title: A Multicenter, Non-randomized, Open-label Dose Escalation Phase Ib Study of Regorafenib in Combination With Pembrolizumab in Patients With Advanced Hepatocellular Carcinoma (HCC) With no Prior Systemic Therapy

This study will determine if the combination of regorafenib and pembrolizumab is safe and tolerated in patients with advanced liver cancer. In addition, the study will explore the anti-tumor activity of this combination as well as potentially identifying blood and tissue biomarkers associated with disease activity, status or response. The study will also investigate how the drugs behave in your body

Being tested
Regorafenib(Stivarga, BAY73-4506), Pembrolizumab
Keywords
Liver cell carcinoma, Liver cancer
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.

  • Regorafenib(Stivarga, BAY73-4506)Drug

    Regorafenib 80mg/120mg/160mg q.d., 3 weeks on / 1 week off + pembrolizumab 200mg i.v. every 3 weeks

  • PembrolizumabDrug

    200 mg i.v.(Intravenous(ly)) every 3 weeks (Q3W). This dose will not be escalated or deescalated and the dosing schedule will not be changed

Study groups in NCT03347292
Study groupRoleWhat they receive
Dose escalationExperimentalThe regorafenib starting dose will be 120 mg q.d.(once daily) 3 weeks on / 1 week off in combination with the recommended dose of pembrolizumab (200 mg Q3W). Pembrolizumab dose will not be escalated or de-escalated.
Receives: Drug: Regorafenib(Stivarga, BAY73-4506); Drug: Pembrolizumab
Dose expansionExperimentalDose expansion cohorts will continue to be expanded until the sample size of 30-35 patients per cohort is reached.
Receives: Drug: Regorafenib(Stivarga, BAY73-4506); Drug: Pembrolizumab

What is being measured

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

  1. Incidence of treatment-emergent adverse event(TEAEs)

    The incidence of treatment-emergent adverse events and treatment-emergent drug-related adverse events summarized in frequency tables using worst CTCAE v4.03 grade.

    Measured: Up to 30 days after last dose of study drug

  2. Severity of TEAEs

    Measured: Up to 30 days after last dose of study drug

  3. Dose Limiting Toxicities(DLTs)

    Measured: Up to 42 days after first treatment administration

Secondary outcomes (8)

  1. Maximum Tolerated Dose (MTD)

    The MTD is defined as the highest dose that can be given so that toxicity probability is below the target toxicity PT =35%.

    Measured: After approximately 18 months

  2. Progression-free survival (PFS)

    Measured: After approximately 36 months

  3. Time to progression (TTP)

    Measured: After approximately 36 months

  4. Overall survival (OS)

    Measured: After approximately 36 months

  5. Overall response rate (ORR)

    Measured: After approximately 36 months

  6. Disease control rate (DCR)

    Measured: After approximately 36 months

  7. Duration of response (DOR)

    Measured: After approximately 36 months

  8. Duration of stable disease

    Measured: After approximately 36 months

Timeline

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

  1. First posted20 Nov 2017
  2. Study start18 Jun 2018
  3. Primary completion17 Dec 2020
  4. Study completion6 Sep 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
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03347292
Sponsor's protocol ID
19497
Other IDs
KN-743, 2017-003202-40, 2017
Status last verified
Jul 2023
First submitted
16 Nov 2017
Last updated
25 Jul 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Regorafenib(Stivarga, BAY73-4506) and Pembrolizumab in people with Carcinoma, Hepatocellular, run by Bayer at 7 sites in 2 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 10 inclusion and 10 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 25 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States, Germany. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 treatment-emergent adverse event(TEAEs) (time frame: Up to 30 days after last dose of study drug). The study lists 3 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 NCT03347292.

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 25 Jul 2023.

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