Study of Safety and Tolerability of PDR001 in Combination With Sorafenib and to Identify the Maximum Tolerated Dose and/or Phase 2 Dose for This Combination in Advanced Hepatocellular Patients

Novartis

Status and phase: Completed; Phase 1

Conditions: Hepatocellular Carcinoma

Treatments: Drug: Sorafenib; Drug: PDR001

Study type: Interventional

Funder types: Industry

Identifiers

NCT02988440

2016-004131-20 (EudraCT Number)

CPDR001G2101

Details and patient eligibility

About

A two part study to determine the maximum tolerated dose and/or recommended phase 2 dose of PDR001 in combination with sorafenib in patients with advanced hepatocellular carcinoma in first line. There will be a dose escalation part and a dose expansion part.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically confirmed advanced (unresectable and/or metastatic) HCC
• Patients with advanced HCC not amenable for surgical or loco-regional treatment
• At least one measureable tumor lesion that that has not been previously locally
• Patients with current cirrhotic status of Child-Pugh class A only (5-6 points with total bilirubin < 2 mg/dL for dose-escalation) with no encephalopathy and no clinical ascites (ascites controlled by diuretics is also excluded in this study).
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Patient must meet required laboratory values at the screening
• Normal electrocardiogram at screening

Exclusion criteria

• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
• Invasion of the main portal vein and/or tumor involvement in more than 50% of the liver (applicable only for the dose-escalation part)
• Patients with Portal-caval shunts
• Prior or concomitant systemic anti-cancer treatment for advanced disease
• Systemic chronic steroid therapy (≥ 10mg/day prednisone or equivalent) or any immunosuppressive therapy 7 days prior to planned date for first dose of study treatment. Topical, inhaled, nasal and ophthalmic steroids are allowed.
• Cardiac or cardiac repolarization abnormality
• Patients with active Hepatitis B infection (HBsAg positive) that are not receiving antiviral treatment are excluded
• Patients with positive test for hepatitis C ribonucleic acid (HCV RNA)
• Loco-regional treatment within 4 weeks prior to initiation of study treatment.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

20 participants in 1 patient group

PDR001 + Sorafenib

Other group

Description:

PDR001 at 400 mg given intravenously every 4 weeks and sorafenib 400 mg taken orally once or twice per day (escalating doses)

Treatment:

Drug: Sorafenib

Drug: PDR001