Phase 3 Study of Lenvatinib (E7080/MK-7902) plus Pembrolizumab (MK- 3475) for First-line Therapy of Advanced Hepatocellular Carcinoma
- Conditions
- Advanced hepatocellular carcinomaMedDRA version: 20.0 Level: PT Classification code 10073071 Term: Hepatocellular carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-002983-26-ES
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 750
1. Have a HCC diagnosis confirmed by radiology, histology, or cytology (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible)
2. Have BCLC Stage C disease, or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach
3. Have a Child-Pugh class A liver score within 7 days prior to first dose of study intervention
4. Have a predicted life expectancy of >3 months
5. Have at least one measurable lesion based on RECIST 1.1 as confirmed by the BICR vendor
6. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 within 7 days prior to first dose of study intervention
7. Participant is male or female
8. Participant is =18 years of age, at the time of signing the informed consent
9. A male participant must agree to use contraception during the treatment period and for at least 120 days after the last dose of study intervention and refrain from donating sperm during this period
10. A female participant is eligible to participate if she is not pregnant not breastfeeding, and at least 1 of the following conditions applies:
a. Not a woman of childbearing potential (WOCBP)
OR
b. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study intervention
11. The participant (or legally acceptable representative if applicable) provides written informed consent/assent for the study
12. Participants with past or ongoing HCV infection will be eligible for the study. The treated participants must have completed their treatment at least 1 month prior to starting study intervention
13. Participants with controlled hepatitis B will be eligible as long as they meet the following criteria:
a) Antiviral therapy for HBV must be given for at least 4 weeks and HBV viral load must be less than 100 IU/mL prior to first dose of study drug. Participants on active HBV therapy with viral loads under 100 IU/mL should stay on the same therapy throughout study treatment
b) Participants who are positive for anti-hepatitis B core antibody HBc, negative for hepatitis B surface antigen (HBsAg), and negative or positive for anti-hepatitis B surface antibody (HBs), and who have an HBV viral load under 100 IU/mL, do not require HBV anti-viral prophylaxis
14. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP =150/90 mm Hg at Screening and no change in antihypertensive medications within 1 week before Cycle 1 Day 1
15. Have adequate organ function
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 450
1.Has had esophageal or gastric variceal bleeding within the last 6 months. All participants will be screened for esophageal varices unless such screening has been performed in the past 12 months before first dose of treatment
2.Bleeding or thrombotic disorders or use of factor X inhibitors or anticoagulants requiring therapeutic international normalized ratio monitoring, eg, warfarin or similar agents. Treatment with low molecular weight heparin is permitted. Antiplatelet agents are prohibited throughout the study
3.Has clinically apparent ascites on physical examination that is not controlled with medication
4.Portal vein invasion at the main portal(Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging
5.Has had clinically diagnosed hepatic encephalopathy in the last 6 months. Participants on rifaximin or lactulose to control their hepatic encephalopathy are not allowed
6.Has medical contraindications that preclude all forms of contrast enhanced imaging(CT or MRI)
7.Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
8.Has a preexisting Grade =3 gastrointestinal or non-gastrointestinal fistula
9.Clinically significant hemoptysis from any source or tumor bleeding within 2 weeks prior to the first dose of study drug
10.Has significant cardiovascular impairment within 12 months of the first dose of study intervention such as history of congestive heart failure greater than New York Heart Association Class II, unstable angina, myocardial infarction or cerebrovascular accident stroke, or cardiac arrhythmia associated with hemodynamic instability
11.Has had major surgery to the liver within 4 weeks prior to the first dose of study intervention
12.Has had a minor surgery within 7 days prior to the first dose of study intervention (Cycle1 Day1)
13.Has serious nonhealing wound, ulcer, or bone fracture
14.Has received any systemic chemotherapy, including anti-VEGF therapy, or any systemic investigational anticancer agents for advanced/unresectable HCC
15.Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PDL2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
16.Has received locoregional therapy to liver within 4 weeks prior to the first dose of study intervention
17.Has received prior radiotherapy to a non-liver region within 2 weeks of start of study intervention
18.Has received a live vaccine within 30 days prior to the first dose of study intervention
19.Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
20.Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention
21.Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
22.Has a known history of, or any evidence of, CNS metastases and/or carcinomatous meningitis as assessed by l
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method