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

December 16, 2020 updated by: Novartis Pharmaceuticals

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Novartis Investigative Site
  • Germany
      • Essen, Germany, 45147
        • Novartis Investigative Site
  • Hong Kong
      • Hong Kong, Hong Kong
        • Novartis Investigative Site
  • Italy
    • MI
      • Rozzano, MI, Italy, 20089
        • Novartis Investigative Site
  • Japan
    • Chiba
      • Kashiwa, Chiba, Japan, 277 8577
        • Novartis Investigative Site
    • Kanagawa
      • Yokohama city, Kanagawa, Japan, 232 0024
        • Novartis Investigative Site
  • Spain
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Novartis Investigative Site
  • Taiwan
      • Taipei, Taiwan, 10002
        • Novartis Investigative Site
  • United States
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
OTHER: PDR001 + Sorafenib
PDR001 at 400 mg given intravenously every 4 weeks and sorafenib 400 mg taken orally once or twice per day (escalating doses)
Drug: PDR001
PDR001 will be administered intravenously
Drug: Sorafenib
Sorafenib is formulated as a tablet.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: From baseline until 30 days of last dose of study treatment
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
Incidendence of Dose Limiting Toxicities (DLTs)
Time Frame: During the first 8 weeks of treatment
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
Dose interruptions
Time Frame: Until end of treatment, assessed for a median time of 4 months
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
Dose reductions
Time Frame: Until end of treatment, assessed for a median time of 4 months
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
Dose intensity
Time Frame: Until end of treatment, assessed for a median time of 4 months
Tolerability measured by the dose intensity of study treatment
Until end of treatment, assessed for a median time of 4 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as per central radiology assessment by dose level
Time Frame: Until end of treatment, assessed for a median time of 4 months
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
PDR001 trough concentration
Time Frame: Pre-dose at Cycle 2, 3, 4, 6 , 8, 10, 12 on Day 1. Cycle=28 days
Concentration of PDR001 in plasma
Pre-dose at Cycle 2, 3, 4, 6 , 8, 10, 12 on Day 1. Cycle=28 days
Maximum concentration (Cmax) of sorafenib
Time Frame: Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
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
Time to reach maximum concentration (Tmax) of sorafenib
Time Frame: Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
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
Area under the plasma concentration-time curve of sorafenib from time zero to 8 hours after administration (AUC0-8)
Time Frame: Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
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
Area Under the Plasma Concentration-time Profile (AUCtau) of sorafenib
Time Frame: Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 20, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 27, 2020

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 27, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 7, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 8, 2016

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 9, 2016

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 19, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 16, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CPDR001G2101
  • 2016-004131-20 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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