Longitudinal Immune-phenotyping of HCC Following MK-3475

  • STATUS
    Recruiting
  • End date
    Jul 29, 2024
  • participants needed
    45
  • sponsor
    National Cancer Centre, Singapore
Updated on 29 June 2022
hepatitis
international normalized ratio
hepatitis b surface antigen
prothrombin
metastasis
neutrophil count
pet scan
pembrolizumab
radiofrequency ablation
hepatectomy

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. 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.

Details
Condition Hepatocellular Carcinoma
Treatment Pembrolizumab
Clinical Study IdentifierNCT04224480
SponsorNational Cancer Centre, Singapore
Last Modified on29 June 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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, 21 - 80 years of age on 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
Lung lesions <1 cm
Without invasion of main portal vein (PV3), or major left and right branches
Future liver remnant of >40%
(PV2)
<5 hepatic lesions in total
Demonstrate adequate organ function as defined in Table 3, all screening labs should be performed within 10 days of neoadjuvant treatment initiation
Have tumor larger than 1.5 cm in size
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): ≤2.5 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
Be scheduled for liver resection within 5-6 weeks
Have Child-Pugh score ≤ 6
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

Exclusion Criteria

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 tumor thrombus involvement in main portal vein (PV3), or major left and right branches (PV2) on pre-operative imaging
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 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%
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 an active infection requiring systemic therapy
Has had a minor surgery ≤ 7 days prior to the first dose of study treatment (Cycle 1, Day 1)
Has dual active HBV infection [HBsAg (+) and/or detectable HBV DNA] and HCV infection [anti-HCV Ab (+) and detectable HCV RNA] at study entry
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