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

NCT02988440 | Completed Phase 1 FDA Drug

• 2 other identifiers: CPDR001G21012016-004131-20
• Study Type: interventional
• Target: 20
• Locations: 8 countries
• Sites: 9

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.

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

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• 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

• Dose intensity

  Tolerability measured by the dose intensity of study treatment

  Until end of treatment, assessed for a median time of 4 months

Secondary Outcomes (6)

• Overall Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as per central radiology assessment by dose level

  Until end of treatment, assessed for a median time of 4 months

• PDR001 trough concentration

  Pre-dose at Cycle 2, 3, 4, 6 , 8, 10, 12 on Day 1. Cycle=28 days

• Maximum concentration (Cmax) of sorafenib

  Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days

• Time to reach maximum concentration (Tmax) of sorafenib

  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)

  Cycle 3 Day 1 Pre-dose, 1h, 3h and 8 h post-dose. Cycle=28 days

Study Arms (1)

PDR001 + Sorafenib

OTHER

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

Drug: PDR001; Drug: Sorafenib

Interventions

PDR001 DRUG

PDR001 will be administered intravenously

PDR001 + Sorafenib

Sorafenib DRUG

Sorafenib is formulated as a tablet.

PDR001 + Sorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (9)

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Novartis Investigative Site

Montreal, Quebec, H3T 1E2, Canada

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Hong Kong, Hong Kong

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Kashiwa, Chiba, 277 8577, Japan

Location

Novartis Investigative Site

Yokohama, Kanagawa, 232 0024, Japan

Location

Novartis Investigative Site

Pamplona, Navarre, 31008, Spain

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

Related Links

• Results for CPDR001G2101 from Novartis Clinical Trials Website

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

spartalizumab; Sorafenib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2016
• First Posted: December 9, 2016
• Study Start: April 20, 2017
• Primary Completion: February 27, 2020
• Study Completion: February 27, 2020
• Last Updated: December 19, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1); ES (1); US (1); CA (1); JP (2); TW (1); IT (1); DE (1)