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Hepatocellular CarcinomaPhase 1NCT04224480

Longitudinal Immune-phenotyping of HCC Following MK-3475

A Phase 1 study testing Pembrolizumab in people with Hepatocellular Carcinoma, run by National Cancer Centre, Singapore at 1 site in Singapore.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The study comprises a main study of pembro-treated HCC patients and a sub-study of untreated HCC patients. In the main study, patients will be treated with pembrolizumab as neoadjuvant treatment approximately 4 weeks prior scheduled surgery. Read more about this study

Who is it for?
Ages 21 to 99 years
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteSingapore
Study dates
10 Dec 2019to 31 Dec 2025
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 21 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Be willing and able to provide written informed consent for the trial. The subject may also provide consent for donation of tissue to the SingHealth Tissue Repository (STR). However, the subject may participate in the trial without participating in STR.
  • Be male or female subject, who is at least 21 years of age on the date of first signed written informed consent
  • Have diagnosis of HCC by AASLD imaging criteria or by cytology/histology.
  • Have technically resectable HCC, with complete extirpation of HCC at end of surgery by resection +/- intra-operative radiofrequency ablation (RFA) at time of enrolment:
  • Without extrahepatic metastases
  • Regional lymph nodes (LN) <2 cm
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  • Lung lesions <1 cm
  • Without invasion of main portal vein (PV3), or major left and right branches (PV2)
  • Future liver remnant of >40%
  • <5 hepatic lesions in total
  • Have tumor larger than 1.5 cm in size
  • Demonstrate adequate organ function as defined in Table 3, all screening labs should be performed within 14 days of neoadjuvant treatment initiation.
  • Absolute neutrophil count (ANC): ≥1,200/mcL
  • Platelets: ≥80,000/ mcL
  • Hemoglobin: ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)
  • Serum creatinine: ≤1.5 X upper limit of normal (ULN) OR creatinine ≥60mL/min for subjects with creatinine >1.5X institutional ULN
  • Serum total bilirubin: ≤ 1.5 X ULN
  • AST (SGOT) and ALT (SGPT): ≤5.0 X ULN
  • Albumin: ≥3.0 g/dL
  • International Normalized Ratio (INR) or Prothrombin Time (PT) AND Activated Partial Thromboplastin Time (aPTT): ≤1.5 X ULN OR within therapeutic range for subjects on anticoagulant therapy. Abnormalities will be corrected prior to liver resection, if necessary according to institution practice
  • Have Child-Pugh score ≤ 6.
  • Be scheduled for liver resection within 5-6 weeks.
  • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Female subjects of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication.
  • Male subjects of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
  • Have a performance status of 0-1 using the ECOG Performance Scale.
  • Have not had treatment for HCV or are not on current anti-HCV treatment for subjects with chronic infection by HCV. For subjects who have had anti-HCV therapy, the last dose of anti-HCV medication should be at least 4 weeks before first dose of pembrolizumab.
  • Have HBV viral load under 100 IU/mL with or without treatment, for subjects with chronic hepatitis B infection. HBV viral load must be less than 100 IU/mL on at least 4 weeks of anti-viral therapy prior to first dose of pembrolizumab. Subjects on active HBV therapy with viral loads under 100 IU/mL should stay on the same therapy throughout study treatment. Subjects who are anti-HBc (+), negative for HBs Ag, negative for anti-HBs, and have an HBV viral load under 100 IU/mL do not require HBV anti-viral prophylaxis.

Who cannot join

  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids may be approved after consultation with the Protocol Chairperson. Physiologic dose of corticosteroid is defined as ≤ 10 mg/day prednisolone or equivalent.
  • Has macrovascular invasion and distant metastases. Definition of metastases includes lymph nodes (LN) ≥ 2 cm in widest diameter and lung lesions ≥ 1 cm in widest diameter).
  • Has tumor thrombus involvement in main portal vein (PV3), or major left and right branches (PV2) on pre-operative imaging.
  • Has a recurrent HCC < 24 months after previous resection.
  • Has had major surgery to any site within 4 weeks prior to the first dose of study drug.
  • Has future liver remnant ≤ 40%.
Show all 28Show fewer
  • Has more than 5 lesions in total.
  • Has encephalopathy.
  • Has history of allergic disease or reactions likely to be exacerbated by any component of pembrolizumab.
  • Has had a solid organ or hematologic transplant.
  • Has had untreated esophageal or gastric variceal bleeding within the last 6 months.
  • Has clinically apparent ascites on physical examination.
  • Has had prior anti-cancer treatment for HCC, except for complete ablation of HCC by liver resection and/or RFA at least 24 months prior to current HCC diagnosis. Anti-cancer treatment includes but is not limited to loco-regional therapy (e.g. TACE, radiotherapy, immunotherapy, chemotherapy or neoadjuvant therapy).
  • Has previous or concomitant malignancies at other sites, except effectively treated non-melanoma carcinoma of the skin or in situ cervical cancer or effectively treated malignancy that has been in remission for more than 5 years and is highly likely to have been cured.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has known history of, or any evidence of active, (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • Has uncontrolled congestive heart failure or hypertension, unstable heart disease (coronary artery disease or myocardial infarction) or any uncontrolled arrhythmia at the time of enrollment into study.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator, including dialysis.
  • Has known psychiatric or addictive disorders that may compromise his/her ability to give informed consent, or to comply with trial procedures.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or if the subject has previously participated in Merck pembrolizumab clinical trials
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has received a live vaccine within 30 days of planned start of study therapy.
  • Is currently participating, or has participated, in a study of an investigational agent and received study therapy, herbal/complementary oral or IV medicine, or used an investigation device within 4 weeks of the first dose of treatment. Subjects must also have recovered from associated therapy (i.e. to Grade ≤ 1 or baseline) and from AEs due to any prior therapy.
  • Has had a minor surgery ≤ 7 days prior to the first dose of study treatment (Cycle 1, Day 1).
  • Has an active infection requiring systemic therapy.
  • Has dual active HBV infection [HBsAg (+) and/or detectable HBV DNA] and HCV infection [anti-HCV Ab (+) and detectable HCV RNA] at study entry.

Trial locations and contacts

1 site in 1 country.

Singapore1 site

  • National Cancer Centre Singapore

    Singapore

Other trials in Singapore

About this study

Official title: Longitudinal Immune-phenotyping of Surgically Resected HCC Following Neoadjuvant and Adjuvant Treatment With MK-3475

The study comprises a main study of pembro-treated HCC patients and a sub-study of untreated HCC patients. In the main study, patients will be treated with pembrolizumab as neoadjuvant treatment approximately 4 weeks prior scheduled surgery. Adjuvant treatment with pembrolizumab with commence at approximately 4 weeks post-surgery for up to 12 months. Subjects will be followed up for a further 12 months after end of treatment for recurrence and survival.

The sub-study is a tumour sample collection study which will provide pre-treatment immune microenvironment data from up to 15 pairs of HCC/adjuvant liver tissue samples. Translational analyses performed for liver tissue samples in the sub-study will be harmonized with the analyses on liver tissue samples collected in the main study.

Being tested
Pembrolizumab
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

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

  • PembrolizumabDrug

    Also called MK-3475

    200mg of intravenous infusion every 3 weeks

Study groups in NCT04224480
Study groupRoleWhat they receive
TreatmentExperimentalNeoadjuvant treatment will consist of one dose of IV pembrolizumab. Tumor resection will be performed approximately 4 weeks after neoadjuvant pembrolizumab. Adjuvant treatment with pembrolizumab will be administered 4 weeks after the surgery.
Receives: Drug: Pembrolizumab

What is being measured

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

  1. Number of subjects with HCC recurrence

    To evaluate the effect of neoadjuvant and adjuvant pembrolizumab on recurrence rate

    Measured: 2 years after hepatic resection

  2. Number of CD8+ Ki67+ T cells found in resected tumour from subjects

    To compare the phenotype of immune cells in the tumor microenvironment after tumor resection from recurrence-free verses recurrent subjects receiving pembrolizumab

    Measured: Up to 24 months after hepatic resection

Timeline

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

  1. First posted13 Jan 2020
  2. Study start10 Dec 2019
  3. Primary completion31 Dec 2025 (estimated)
  4. Study completion31 Dec 2025 (estimated)

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
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04224480
Sponsor's protocol ID
NCCS-OTSP-HCC1
Status last verified
Jan 2024
First submitted
8 Jan 2020
Last updated
19 Jan 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Gao Q, Wang XY, Qiu SJ, Yamato I, Sho M, Nakajima Y, Zhou J, Li BZ, Shi YH, Xiao YS, Xu Y, Fan J. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res. 2009 Feb 1;15(3):971-9. doi: 10.1158/1078-0432.CCR-08-1608.

    PubMed 19188168

  • Welker MW, Bechstein WO, Zeuzem S, Trojan J. Recurrent hepatocellular carcinoma after liver transplantation - an emerging clinical challenge. Transpl Int. 2013 Feb;26(2):109-18. doi: 10.1111/j.1432-2277.2012.01562.x. Epub 2012 Sep 21.

    PubMed 22994652

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pembrolizumab in people with Hepatocellular Carcinoma, run by National Cancer Centre, Singapore at 1 site in Singapore.

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 28 inclusion and 28 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 19 Jan 2024. 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 Singapore. 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?

Results are not available in the source record.

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?

Number of subjects with HCC recurrence (time frame: 2 years after hepatic resection). 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?

On the ClinicalTrials.gov record for NCT04224480, which also lists 2 linked publications.

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 19 Jan 2024.

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