A Phase III Study of Pembrolizumab (MK 3475) plus Best Supportive Care in Subjects with Advanced Hepatocellular Carcinoma
- Conditions
- Hepatocellular CarcinomaTherapeutic area: Diseases [C] - Cancer [C04]MedDRA version: 21.0Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectableSystem Organ Class: 100000004864
- Registration Number
- EUCTR2015-004567-36-DK
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 408
1. Be willing and able to provide written informed consent for the trial. The subject may also provide consent for Future Biomedical Research (FBR). However, the subject may participate in the main trial without participating in FBR.
2. Be 18 years of age on day of signing informed consent.
3. Have a HCC diagnosis confirmed by radiology, histology, or cytology (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible). Radiologic confirmation diagnosis is provided by the study site. Definition of radiological confirmation: Clinical findings consistent with the diagnosis of liver cirrhosis and a liver mass measuring at least 2 cm with characteristic vascularization (intense enhancement seen in the hepatic arterial-dominant phase and contrast washout in the late portal venous phase) seen in either
triphasic computed tomography (CT) scan or magnetic resonance imaging (MRI).
4. Have Barcelona Clinic Liver Cancer (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 (see Section 12.8).
5. Have a Child-Pugh class A liver score within 7 days of first dose of study drug.
6. Have a predicted life expectancy of >3 months.
7. Have at least one measurable lesion based on RECIST 1.1 as confirmed by the blinded central imaging vendor.
8. Have a performance status of 0 or 1 using the ECOG Performance Scale within 7 days of first dose of study drug.
9. Have documented objective radiographic progression during or after treatment with sorafenib or intolerance to sorafenib. Sorafenib intolerance definition:
Any Grade =2 drug-related AE which 1) despite supportive therapy, recurred after sorafenib treatment interruption of at least 7 days and dose reduction resulting in the subject requesting, or the physician recommending
discontinuation due to toxicity. OR 2) required discontinuation of sorafenib due to toxicity, recommended by the physician with no rechallenge.
10. Subjects with chronic infection by HCV who are treated (successfully or treatment failure) or untreated are allowed on study. In addition, subjects with successful HCV
treatment are allowed as long as there are =4 weeks between achieving sustained viral response (SVR12) and start of study drug. Successful HCV treatment definition: SVR12.
11. Has been treated with anti-Hepatitis B therapy.
Controlled (treated) hepatitis B subjects will be allowed if they meet the following criteria:
Antiviral therapy for HBV must be given for at least 12 weeks and HBV viral load must be less than 100 IU/mL prior to first dose of study drug. 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 HBsAg, and negative or positive for anti-HBs, and who have an HBV viral load under 100 IU/mL do not require HBV anti-viral prophylaxis.
12. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication (Cycle 1, Day 1). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
will be required.
13. Female subjects of childbearing potential (Section 5.7.2) must be willing to use an adequate method of contraception as outlined in Section 5.7.2 – Contraception for the course of the study, starting with the first dose of study medication
1. 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.
2. Has received sorafenib within 14 days of first dose of study medication.
3. Has had esophageal or gastric variceal bleeding within the last 6 months. All subjects will be screened for esophageal varices, unless such screening has been performed in the past 12 months before first dose of treatment. If varices are present, they should
be treated according to institutional standards before starting study treatment.
4. Has clinically apparent ascites on physical examination.
5. Portal vein invasion at the main portal (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging.
6. Has had clinically diagnosed hepatic encephalopathy in the last 6 months. Subjects on rifaximin or lactulose to control their hepatic encephalopathy are not allowed.
7. Had a solid organ or hematologic transplant.
8. Had prior systemic therapy for HCC in the advanced (incurable) setting other than sorafenib, prior to start study drug.
9. Has a known severe hypersensitivity (= Grade 3) to pembrolizumab, its active substance and/or any of its excipients. (Refer to the respective Investigator’s
Brochure for a list of excipients.)
10. Has active autoimmune disease that has required systemic treatment in 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.
11. 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 Sponsor
12. Has received locoregional therapy to liver ranscatheter chemoembolization [TACE], transcatheter embolization [TAE], hepatic arterial infusion [HAI], radiation,
radioembolization, or ablation) within 4 weeks prior to the first dose of study drug. Subject is not eligible if aforementioned treatments were administered
between last dose of sorafenib and first dose of study medication.
13. Has had major surgery to liver or other site within 4 weeks prior to the first dose of study drug.
14. Has had a minor surgery (i.e., simple excision, tooth extraction) =7 days prior to the first dose of study treatment (Cycle 1, Day 1).
15. Has not recovered adequately (i.e., Grade =1 or baseline) from the toxicity and/or
complications from any intervention prior to starting therapy.
16. Has a diagnosed additional malignancy within 3 years prior to first dose of study with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cancers.
17. Has a known history of, or any evidence of, central nervous system (CNS) metastases and/or carcinomatous meningitis as assessed by local site investigator.
18. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
19. Has an active infection requiring systemic therapy.
20. Has
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