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

Hepatocellular Carcinoma Clinical Trial

Official title:

A Phase Ib Study of PDR001 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02988440
• Other study ID #: CPDR001G2101
• Secondary ID: 2016-004131-20
• Status: Completed
• Phase: Phase 1
• Start date: April 20, 2017
• Est. completion date: February 27, 2020

Study information

• Verified date: September 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: February 27, 2020
• Est. primary completion date: February 27, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• PDR001
PDR001 will be administered intravenously
• Sorafenib
Sorafenib is formulated as a tablet.

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Montreal	Quebec
Germany	Novartis Investigative Site	Essen
Hong Kong	Novartis Investigative Site	Hong Kong
Italy	Novartis Investigative Site	Rozzano	MI
Japan	Novartis Investigative Site	Kashiwa	Chiba
Japan	Novartis Investigative Site	Yokohama city	Kanagawa
Spain	Novartis Investigative Site	Pamplona	Navarra
Taiwan	Novartis Investigative Site	Taipei
United States	Karmanos Cancer Institute	Detroit	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Hong Kong,  Italy,  Japan,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	Incidence and severity of AEs and SAEs, including changes in laboratory vital signs and ECGs	From baseline until 30 days of last dose of study treatment
Primary	Incidendence of Dose Limiting Toxicities (DLTs)	A dose-limiting toxicity (DLT) was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications that met certain criteria as defined in the protocol.	During the first 8 weeks of treatment
Primary	Dose interruptions	Tolerability measured by the number of subjects who have interruptions of study treatment	Until end of treatment, assessed for a median time of 4 months
Primary	Dose reductions	Tolerability measured by the number of subjects who have reductions of study treatment	Until end of treatment, assessed for a median time of 4 months
Primary	Dose intensity	Tolerability measured by the dose intensity of study treatment	Until end of treatment, assessed for a median time of 4 months
Secondary	Overall Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as per central radiology assessment by dose level	Overall response rate (ORR) as per the independent central radiology assessment will be summarized descriptively by dose level. The overall response rate (ORR) is defined as the proportion of patients with best overall response of CR or PR. The best overall response is the best response recorded using the independent central radiology review based on RECIST 1.1 from start of treatment until disease progression, death, start of new therapy, withdrawal of consent or cut-off date, whichever occurs first	Until end of treatment, assessed for a median time of 4 months
Secondary	PDR001 trough concentration	Concentration of PDR001 in plasma	Pre-dose at Cycle 2, 3, 4, 6 , 8, 10, 12 on Day 1. Cycle=28 days
Secondary	Maximum concentration (Cmax) of sorafenib	The maximum (peak) observed plasma, drug concentration after single dose administration.	Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
Secondary	Time to reach maximum concentration (Tmax) of sorafenib	The time to reach maximum (peak) plasma drug concentration after single dose administration (time)	Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
Secondary	Area under the plasma concentration-time curve of sorafenib from time zero to 8 hours after administration (AUC0-8)	Area under the plasma concentration-time curve of sorafenib from time zero to time 't' where t is a defined time point after administration. t=8 hours (AUC0-8)	Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
Secondary	Area Under the Plasma Concentration-time Profile (AUCtau) of sorafenib	Area under the plasma concentration-time curve from time zero to the end of the dosing interval tau at steady-state	Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days

External Links

•   Results for CPDR001G2101 from Novartis Clinical Trials Website