Unresectable Hepatocellular CarcinomaPhase 1/2NCT05286320
Phase Ib/II Trial of Combining Pembrolizumab and Lenvatinib With SBRT for HCC Patients With Portal Vein Thrombosis.
A Phase 1/2 study testing Lenvatinib/Pembrolizumab plus SBRT combinations in people with Unresectable Hepatocellular Carcinoma and Pembrolizumab, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
HCC patients with PVTT (main trunk or the first-degree branch) treated with the combination of pembrolizumab (Ketruda), lenvatinib (Lenvima), and SBRT. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Unresectable Hepatocellular Carcinoma, Pembrolizumab, Lenvatinib
- What is being tested?
- Lenvatinib/Pembrolizumab plus SBRT combinations
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Mar 2023to 30 Sep 2026
- Phase
- Phase 1/2
- 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 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male/female participants who are at least 20 years of age on the day of signing informed consent with histologically confirmed diagnosis of HCC or those diagnosed by the EASL non-invasive criteria for HCC will be enrolled in this study.
- Male participants:
- A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 220 days after the last dose of study treatment and refrain from donating sperm during this period.
- A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
- Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
- A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 150 days after the last dose of study treatment.
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- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- Have measurable disease based on mRECIST.
- Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
- Have adequate organ function as defined in the following criteria (Specimens must be collected within 10 days prior to the start of study intervention) :(1)Absolute neutrophil count (ANC) ≥1500/µL. (2)Platelets ≥100000/µL. (3)Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L. (4)Creatinine OR Measured or calculatedb creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN. (5)Total bilirubin ≤1.5 ×ULN (mg/dL) OR direct bilirubin ≤ULN for participants with total bilirubin levels >2.5 × ULN (mg/dL).(6)AST (SGOT) and ALT (SGPT) ≤5 × ULN. (7)Alkaline phosphatase ≤2 × ULN.(8)Child-Pugh class Class A. (9)International normalized ratio (INR) OR prothrombin time (PT)、Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants.
- Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening. Participants must have completed curative anti-viral therapy at least 4 weeks prior to starting study intervention. Participants with HBV will be eligible as long as they meet the following criteria: (1) Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to starting study intervention. (2)Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.
- Patients have PVTT in the main trunk (VP4) or central branch (VP3).
- Previous liver resection, embolization, or ablative therapy is permitted.
Who cannot join
- A WOCBP who has a positive urine pregnancy test within 72 hours prior to [allocation]. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
- Has received prior systemic anti-HCC therapy including investigational agents or other local therapy within 4 weeks prior to [allocation].
- Has received prior radiotherapy to non-liver sites within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
- 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 or modulation therapy within 7 days prior to the first dose of study drug.
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- Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
- Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab/Lenvatinib and/or any of their excipients.
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a known history of Human Immunodeficiency Virus (HIV) infection.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
- Has had an allogenic tissue/solid organ transplant.
- Child-Pugh class B or C cirrhosis of liver.
- Patients with a history of selective internal radiation therapy (eg, microsphere radioembolization) or who have received radiotherapy to the abdominal area prior to the initiation of study treatment.
- Patients who have an inadequate hepatic reserve, as judged by the investigator; ie, normal liver tissue volume <700 mL.
- Patients who fail to follow the radiation dose constraint of any critical organ.
- Has a preexisting Grade ≥3 gastrointestinal or non-gastrointestinal fistula.
- Has clinically significant hemoptysis from any source or tumor bleeding within 2 weeks prior to the first dose of study intervention.
- Has significant cardiovascular impairment within 12 months prior to the first dose of study intervention such as history of congestive heart failure greater than NYHA Class II, unstable angina, myocardial infarction or cerebrovascular accident stroke, or cardiac arrhythmia associated with hemodynamic instability.
- Has had major surgery to the liver within 4 weeks prior to the first dose of study intervention.
- Note: f participant underwent major surgery, they must have adequately recovered from the toxicity and/or complications from the intervention prior to starting study intervention.
- Has had a minor surgery (ie, simple excision) within 7 days prior to the first dose of study intervention (Cycle 1 Day 1).
- Has serious nonhealing wound, ulcer, or bone fracture.
- Participants with proteinuria >1+ on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein ≥1 g/24 hours will be ineligible.
- Has prolongation of corrected QT (QTc) interval to >480 ms (corrected by Fridericia Formula) or is taking drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics (Quinidine, Procainamide, Disopyramide, Amiodarone, Sotalol, Ibutilide, Dofetilide \& Dronedarone).
- Has LVEF below the institutional normal range as determined by MUGA or echocardiogram (ECHO).
- Has dual active HBV infection (HbsAg positive and /or detectable HBV DNA) and HCV infection (anti-HCV Ab positive and detectable HCV RNA) at study entry.
- Uncontrolled blood pressure > 140/90 mmHg in spite of an optimal regimen of antihypertensive medication.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site
National Taiwan University Hospital
Taipei, Taiawn, 100
Chia-Hsien Cheng, 0972-651-680, jasoncheng@ntu.edu.tw
About this study
Official title: Phase Ib/II Trial of Combining Pembrolizumab and Lenvatinib With Stereotactic Body Radiotherapy for Hepatocellular Carcinoma Patients With Portal Vein Thrombosis.
HCC patients with PVTT (main trunk or the first-degree branch) treated with the combination of pembrolizumab (Ketruda), lenvatinib (Lenvima), and SBRT.
Read the detailed description
Protocol treatment includes : Pembrolizumab is intravenously infused every 3 weeks and lenvatinib is orally given every day for a total of 2 years. SBRT (5 fractions within 17 days) to the PVTT and adjacent connecting HCC tumor is delivered in the second cycle of pembrolizumab, with the discontinuation of lenvatinib 7 days before and after SBRT.
- Conditions
- Unresectable Hepatocellular Carcinoma, Pembrolizumab, Lenvatinib, Stereotactic Body Radiotherapy
- Being tested
- Lenvatinib/Pembrolizumab plus SBRT combinations
- Keywords
- Unresectable Hepatocellular Carcinoma, Immunotherapy, Stereotactic body radiotherapy, targeted therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lenvatinib/Pembrolizumab plus SBRT combinationsDrug
Also called Lenvima, Keytruda
Five-fraction SBRT (week 4-week 5) to PVTT and connected HCC tumor in 2 weeks Lenvatinib 12/8 mg/day for 96 weeks (no lenvatinib from 7 day before SBRT to 7 days after SBRT) Pembrolizumab 200 mg q 3 week x 32 cycles
| Study group | Role | What they receive |
|---|---|---|
| Target-/Immuno-therapy for advanced HCC w PVTT Lenvatinib/Pembrolizumab plus SBRT combinations | Experimental | Five-fraction SBRT (week 4-week 5) to PVTT and connected HCC tumor in 2 weeks Lenvatinib 12/8 mg/day for 96 weeks (no lenvatinib from 7 day before SBRT to 7 days after SBRT) Pembrolizumab 200 mg q 3 week x 32 cycles Receives: Drug: Lenvatinib/Pembrolizumab plus SBRT combinations |
What is being measured
The primary outcome is the main question the study is designed to answer.
safety rate
In stage 0 and stage I interim analysis DLT will be assessed after 3 patients for each stage are accrued to the study. In stage II interim analysis for 6 (from stage 0 and I) + 6 (from stage II) patients, ≤4 patients with DLT and ≥6 patients with CR/PR are the criteria for stage III patient accrual.
Measured: The period to evaluate DLT is for 28 days after completion of SBRT.
objective response rate
Tumor measurements and response evaluations are conducted by an independent radiologist based on liver dynamic CT or MRI images at screening and every follow-up image after allocation. A second radiologist will perform an independent blinded image review at the end of the study without interfering with the primary judgment concerning disease progression and treatment decision. The response evaluation criteria are according to mRECIST.
Measured: From date of study intervention to 2.5 years
Secondary outcomes (1)
Progression-free survival and overall survival
Survival outcomes are calculated from date of allocation. Progression is defined as progressive disease by mRECIST or death from any cause. Overall survival is the time from allocation to death from any cause. Survival curves are determined by the Kaplan-Meier method.
Measured: From date of study intervention to 2.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2022
- Study start1 Mar 2023 (estimated)
- Primary completion30 Sep 2026 (estimated)
- Study completion30 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unresectable Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chia-Hsien Cheng, Principal investigator, Department of Internal Medicine, NTUH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05286320
- Sponsor's protocol ID
- 202108042MIPA
- Status last verified
- Sep 2022
- First submitted
- 6 Feb 2022
- Last updated
- 2 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib/II Trial of Combining Pembrolizumab and Lenvatinib With Stereotactic Body Radiotherapy for Hepatocellular Carcinoma Patients With Portal Vein Thrombosis.
- ClinicalTrials.gov ID
- NCT05286320
- Acronym / sponsor ID
- 202108042MIPA
- Conditions
- Unresectable Hepatocellular Carcinoma, Pembrolizumab, Lenvatinib, Stereotactic Body Radiotherapy
- Keywords
- Unresectable Hepatocellular Carcinoma, Immunotherapy, Stereotactic body radiotherapy, targeted therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- 1 Mar 2023 (estimated)
- Primary completion
- 30 Sep 2026 (estimated)
- Study completion
- 30 Sep 2026 (estimated)
- First posted
- 18 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
HCC patients with PVTT (main trunk or the first-degree branch) treated with the combination of pembrolizumab (Ketruda), lenvatinib (Lenvima), and SBRT.
Detailed description
Protocol treatment includes : Pembrolizumab is intravenously infused every 3 weeks and lenvatinib is orally given every day for a total of 2 years. SBRT (5 fractions within 17 days) to the PVTT and adjacent connecting HCC tumor is delivered in the second cycle of pembrolizumab, with the discontinuation of lenvatinib 7 days before and after SBRT.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Target-/Immuno-therapy for advanced HCC w PVTT Lenvatinib/Pembrolizumab plus SBRT combinations | Experimental | Drug: Lenvatinib/Pembrolizumab plus SBRT combinationsFive-fraction SBRT (week 4-week 5) to PVTT and connected HCC tumor in 2 weeks Lenvatinib 12/8 mg/day for 96 weeks (no lenvatinib from 7 day before SBRT to 7 days after SBRT) Pembrolizumab 200 mg q 3 week x 32 cycles |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Male/female participants who are at least 20 years of age on the day of signing informed consent with histologically confirmed diagnosis of HCC or those diagnosed by the EASL non-invasive criteria for HCC will be enrolled in this study.
- Male participants:
- A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 220 days after the last dose of study treatment and refrain from donating sperm during this period.
- A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies:
- The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
Key exclusion criteria (33 listed)
- A WOCBP who has a positive urine pregnancy test within 72 hours prior to [allocation]. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
- Has received prior systemic anti-HCC therapy including investigational agents or other local therapy within 4 weeks prior to [allocation].
- Has received prior radiotherapy to non-liver sites within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
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 |
|---|---|---|
| Lenvatinib/Pembrolizumab plus SBRT combinationsAlso: Lenvima, KeytrudaFive-fraction SBRT (week 4-week 5) to PVTT and connected HCC tumor in 2 weeks Lenvatinib 12/8 mg/day for 96 weeks (no lenvatinib from 7 day before SBRT to 7 days after SBRT) Pembrolizumab 200 mg q 3 week x 32 cycles | Drug | Target-/Immuno-therapy for advanced HCC w PVTT Lenvatinib/Pembrolizumab plus SBRT combinations |
Primary outcome
safety rate
Time frame: The period to evaluate DLT is for 28 days after completion of SBRT.
In stage 0 and stage I interim analysis DLT will be assessed after 3 patients for each stage are accrued to the study. In stage II interim analysis for 6 (from stage 0 and I) + 6 (from stage II) patients, ≤4 patients with DLT and ≥6 patients with CR/PR are the criteria for stage III patient accrual.
objective response rate
Time frame: From date of study intervention to 2.5 years
Tumor measurements and response evaluations are conducted by an independent radiologist based on liver dynamic CT or MRI images at screening and every follow-up image after allocation. A second radiologist will perform an independent blinded image review at the end of the study without interfering with the primary judgment concerning disease progression and treatment decision. The response evaluation criteria are according to mRECIST.
1 secondary outcome
Progression-free survival and overall survival
Time frame: From date of study intervention to 2.5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2023.
- Individual participant dataSharing planned: No
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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.
Chia-Hsien Cheng principal investigator
Department of Internal Medicine, NTUH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Lenvatinib/Pembrolizumab plus SBRT combinations in people with Unresectable Hepatocellular Carcinoma and Pembrolizumab, run by National Taiwan University Hospital at 1 site in Taiwan.
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 13 inclusion and 33 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: status not confirmed, as of the sponsor's last update on 2 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Chia-Hsien Cheng (+886972651680, jasoncheng@ntu.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
safety rate (time frame: The period to evaluate DLT is for 28 days after completion of SBRT.). 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?
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 2 Mar 2023.