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Completed

NCT Number: 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

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.

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Key information

Conditions

Hepatocellular Carcinoma Adenocarcinoma Carcinoma Carcinoma, Hepatocellular Digestive System Diseases Digestive System Neoplasms Liver Diseases Liver Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Novartis Investigative Site, Montreal, Quebec, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

PDR001

Drug

PDR001 will be administered intravenously

Sorafenib

Drug

Sorafenib is formulated as a tablet.

Primary outcomes

  1. 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

  2. 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.

  3. 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

  4. 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

  5. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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.

  4. 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)

  5. 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)

  6. 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

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

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

Important dates

Study start
2017
Primary completion
2020
Study completion
2020
First posted
Dec 9, 2016
Registry last updated
Dec 19, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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