Clinical trial NCT02988440: 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
Official title: A Phase Ib Study of PDR001 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatocellular Carcinoma
Keywords: HCC
Hepatocellular carcinoma
Hepatocellular carcinoma (HCC)
PDR001
liver cancer
immunotherapy liver
malignant hepatoma
Hepatocellular cancer
advanced hepatocellular carcinoma (HCC)
advanced liver cancer
liver cancer progression
sorafenib
anti-PD1
first line
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-12-09
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From baseline until 30 days of last dose of study treatment
measure: Incidendence of Dose Limiting Toxicities (DLTs)
timeFrame: During the first 8 weeks of treatment
measure: Dose interruptions
timeFrame: Until end of treatment, assessed for a median time of 4 months
measure: Dose reductions
timeFrame: Until end of treatment, assessed for a median time of 4 months
measure: Dose intensity
timeFrame: Until end of treatment, assessed for a median time of 4 months
Secondary outcomes:
measure: Overall Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as per central radiology assessment by dose level
timeFrame: Until end of treatment, assessed for a median time of 4 months
measure: PDR001 trough concentration
timeFrame: Pre-dose at Cycle 2, 3, 4, 6 , 8, 10, 12 on Day 1. Cycle=28 days
measure: Maximum concentration (Cmax) of sorafenib
timeFrame: Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
measure: Time to reach maximum concentration (Tmax) of sorafenib
timeFrame: Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
measure: Area under the plasma concentration-time curve of sorafenib from time zero to 8 hours after administration (AUC0-8)
timeFrame: Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
measure: Area Under the Plasma Concentration-time Profile (AUCtau) of sorafenib
timeFrame: Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Kashiwa
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Yokohama city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Pamplona
country: Spain
facility: Novartis Investigative Site
state: Navarra
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: