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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

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ClinicalTrials.gov Identifier: NCT02988440
Recruitment Status : Active, not recruiting
First Posted : December 9, 2016
Last Update Posted : March 25, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: PDR001 Drug: Sorafenib Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib Study of PDR001 in Combination With Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC)
Actual Study Start Date : April 20, 2017
Estimated Primary Completion Date : November 25, 2019
Estimated Study Completion Date : November 28, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
PDR001 + Sorafenib Drug: PDR001
PDR001 will be administered intravenously

Drug: Sorafenib
Sorafenib is formulated as a tablet.




Primary Outcome Measures :
  1. Number of participants with Adverse Events (AEs) as a measure of safety and tolerability [ Time Frame: continuous until 150 days after last treatment ]

Secondary Outcome Measures :
  1. Pharmacokinetics (PK): Ctrough [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day one of cycles 3, 4, 6, 8, 10, 12 and Day 1 of every 6th cycle thereafter, end of treatment and 30 days after last dose ]
  2. Pharmacokinetics (PK): Cmax [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day one of cycles 3, 4, 6, 8, 10, 12 and Day 1 of every 6th cycle thereafter, end of treatment and 30 days after last dose ]
  3. Pharmacokinetics (PK): AUC [ Time Frame: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Day one of cycles 3, 4, 6, 8, 10, 12 and Day 1 of every 6th cycle thereafter, end of treatment and 30 days after last dose ]
  4. Overall response rate (ORR) using RECIST v1.1 criteria) [ Time Frame: Baseline, every 8 weeks until progression up to 1 year after last patient first treatment ]
    RECIST v1.1 = Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  5. Progression free survival (PFS) [ Time Frame: Baseline, every 8 weeks until progression up to 1 year after last patient first treatment ]
  6. Time to Progression (TTP) [ Time Frame: Baseline, every 8 weeks until progression up to 1 year after last patient first treatment ]
  7. Duration of response (DOR) [ Time Frame: Baseline, every 8 weeks until progression up to 1 year after last patient first treatment ]
  8. Time to response (TTR) [ Time Frame: Baseline, every 8 weeks until progression up to 1 year after last patient first treatment ]
  9. Disease control rate (DCR) per RECIST v1.1 [ Time Frame: Baseline, every 8 weeks until progression up to 1 year after last patient first treatment ]
  10. Overall survival (OS) [ Time Frame: Every 3 months after last visit up to 2 year after last patient first treatment ]
  11. Antidrug antibodies (ADA) prevalence at baseline and on treatment [ Time Frame: Day one of cycles 1, 2, 3, 4, 6, 8, 10, 12 and Day 1 of every 6th cycle thereafter, end of treatment and 30 days after last dose ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02988440


Locations
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United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Canada, Quebec
Novartis Investigative Site
Montreal, Quebec, Canada, H3T 1E2
France
Novartis Investigative Site
Clichy, France, 92110
Germany
Novartis Investigative Site
Essen, Germany, 45147
Hong Kong
Novartis Investigative Site
Hong Kong, Hong Kong
Italy
Novartis Investigative Site
Rozzano, MI, Italy, 20089
Japan
Novartis Investigative Site
Kashiwa, Chiba, Japan, 277 8577
Novartis Investigative Site
Yokohama city, Kanagawa, Japan, 232 0024
Spain
Novartis Investigative Site
Pamplona, Navarra, Spain, 31008
Switzerland
Novartis Investigative Site
Bern, Switzerland, 3010
Taiwan
Novartis Investigative Site
Taipei, Taiwan, 10002
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02988440     History of Changes
Other Study ID Numbers: CPDR001G2101
2016-004131-20 ( EudraCT Number )
First Posted: December 9, 2016    Key Record Dates
Last Update Posted: March 25, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
PDR001
HCC
Hepatocellular carcinoma
Hepatocellular carcinoma (HCC)
liver cancer
immunotherapy liver
malignant hepatoma
Hepatocellular cancer
advanced hepatocellular carcinoma (HCC)
advanced liver cancer
liver cancer progression
sorafenib
anti-PD1
first line

Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Sorafenib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action