search
Back to results

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

Primary Purpose

Hepatocellular Carcinoma

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
PDR001
Sorafenib
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Karmanos Cancer Institute
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

PDR001 + Sorafenib

Arm Description

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

Outcomes

Primary Outcome Measures

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
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.
Dose interruptions
Tolerability measured by the number of subjects who have interruptions of study treatment
Dose reductions
Tolerability measured by the number of subjects who have reductions of study treatment
Dose intensity
Tolerability measured by the dose intensity of study treatment

Secondary Outcome Measures

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
PDR001 trough concentration
Concentration of PDR001 in plasma
Maximum concentration (Cmax) of sorafenib
The maximum (peak) observed plasma, drug concentration after single dose administration.
Time to reach maximum concentration (Tmax) of sorafenib
The time to reach maximum (peak) plasma drug concentration after single dose administration (time)
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)
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

Full Information

First Posted
December 7, 2016
Last Updated
December 16, 2020
Sponsor
Novartis Pharmaceuticals
search

1. Study Identification

Unique Protocol Identification Number
NCT02988440
Brief Title
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

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
April 20, 2017 (Actual)
Primary Completion Date
February 27, 2020 (Actual)
Study Completion Date
February 27, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PDR001 + Sorafenib
Arm Type
Other
Arm Description
PDR001 at 400 mg given intravenously every 4 weeks and sorafenib 400 mg taken orally once or twice per day (escalating doses)
Intervention Type
Drug
Intervention Name(s)
PDR001
Intervention Description
PDR001 will be administered intravenously
Intervention Type
Drug
Intervention Name(s)
Sorafenib
Intervention Description
Sorafenib is formulated as a tablet.
Primary Outcome Measure Information:
Title
Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
Incidence and severity of AEs and SAEs, including changes in laboratory vital signs and ECGs
Time Frame
From baseline until 30 days of last dose of study treatment
Title
Incidendence of Dose Limiting Toxicities (DLTs)
Description
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.
Time Frame
During the first 8 weeks of treatment
Title
Dose interruptions
Description
Tolerability measured by the number of subjects who have interruptions of study treatment
Time Frame
Until end of treatment, assessed for a median time of 4 months
Title
Dose reductions
Description
Tolerability measured by the number of subjects who have reductions of study treatment
Time Frame
Until end of treatment, assessed for a median time of 4 months
Title
Dose intensity
Description
Tolerability measured by the dose intensity of study treatment
Time Frame
Until end of treatment, assessed for a median time of 4 months
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as per central radiology assessment by dose level
Description
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
Time Frame
Until end of treatment, assessed for a median time of 4 months
Title
PDR001 trough concentration
Description
Concentration of PDR001 in plasma
Time Frame
Pre-dose at Cycle 2, 3, 4, 6 , 8, 10, 12 on Day 1. Cycle=28 days
Title
Maximum concentration (Cmax) of sorafenib
Description
The maximum (peak) observed plasma, drug concentration after single dose administration.
Time Frame
Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
Title
Time to reach maximum concentration (Tmax) of sorafenib
Description
The time to reach maximum (peak) plasma drug concentration after single dose administration (time)
Time Frame
Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
Title
Area under the plasma concentration-time curve of sorafenib from time zero to 8 hours after administration (AUC0-8)
Description
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)
Time Frame
Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
Title
Area Under the Plasma Concentration-time Profile (AUCtau) of sorafenib
Description
Area under the plasma concentration-time curve from time zero to the end of the dosing interval tau at steady-state
Time Frame
Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Novartis Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
Novartis Investigative Site
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Novartis Investigative Site
City
Hong Kong
Country
Hong Kong
Facility Name
Novartis Investigative Site
City
Rozzano
State/Province
MI
ZIP/Postal Code
20089
Country
Italy
Facility Name
Novartis Investigative Site
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
277 8577
Country
Japan
Facility Name
Novartis Investigative Site
City
Yokohama city
State/Province
Kanagawa
ZIP/Postal Code
232 0024
Country
Japan
Facility Name
Novartis Investigative Site
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17724
Description
Results for CPDR001G2101 from Novartis Clinical Trials Website

Learn more about this trial

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

We'll reach out to this number within 24 hrs