Clinical Trials /

Phase Ib/II Study of INC280 + PDR001 or PDR001 Single Agent in Advanced HCC

NCT02795429

Description:

The purpose of this study of INC280 and PDR001 is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of PDR001 administered i.v. as a single agent or in combination with INC280 administered orally in adult patients with advanced hepatocellular carcinoma (HCC).

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase Ib/II Study of INC280 + PDR001 or PDR001 Single Agent in Advanced HCC
  • Official Title: A Phase Ib/II, Open-label, Multi-center Study of INC280 in Combination With PDR001 or PDR001 Single Agent in Advanced Hepatocellular Carcinoma.

Clinical Trial IDs

  • ORG STUDY ID: CINC280X2108
  • SECONDARY ID: 2015-005417-76
  • NCT ID: NCT02795429

Conditions

  • Advanced Hepatocellular Carcinoma

Interventions

DrugSynonymsArms
PDR001INC280+PDR001
INC280INC280+PDR001

Purpose

The purpose of this study of INC280 and PDR001 is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of PDR001 administered i.v. as a single agent or in combination with INC280 administered orally in adult patients with advanced hepatocellular carcinoma (HCC).

Trial Arms

NameTypeDescriptionInterventions
INC280+PDR001ExperimentalPDR001 + INC280 treatment in Phase II
  • PDR001
  • INC280
PDR001 single agentExperimentalPDR001 single agent treatment in Phase II
  • PDR001

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically or cytologically documented locally advanced recurrent or metastatic
             HCC or for patients with cirrhosis according to the American Association for the Study
             of Liver Diseases (AASLD) and Asian Pacific Association for the study of the liver
             (APASL) criteria. Current cirrhotic status of Child Pugh Class A (5-6 points), with no
             encephalopathy and/or clinically significant ascites (defined as requiring the use of
             diuretics or paracentesis treatment).

          2. Patients must have received prior systemic sorafenib treatment for HCC with documented
             progression during or after discontinuation of sorafenib treatment (for France only:
             patients must have received at least 8 weeks of prior sorafenib treatment), or are
             intolerant to sorafenib (defined as documented Grade 3 or 4 adverse events that led to
             sorafenib discontinuation),.

          3. ECOG Performance Status ≤ 1.

          4. Willing and able to swallow and retain oral medication. Other protocol defined
             Inclusion criteria may apply.

        Exclusion Criteria:

          1. Use of any live vaccines within 4 weeks of initiation of study treatment.

          2. History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs).

          3. Clinically significant pleural effusion that either required pleurocentesis or is
             associated with shortness of breath.

          4. Active autoimmune disease or a documented history of autoimmune disease.

          5. Clinically significant, uncontrolled heart diseases.

          6. Patient having out of range laboratory values defined as:

               -  Total bilirubin > 2 mg/dL, except for patients with Gilbert's syndrome who are
                  excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN

               -  Alanine aminotransferase (ALT) > 5 x ULN

               -  Aspartate aminotransferase (AST) > 5 x ULN

               -  Coagulation: Prothrombin Time (PT) > 4 seconds more than the ULN or International
                  Normalized Ratio (INR) > 1.7

               -  Absolute neutrophil count (ANC) < 1.5 x 109/L

               -  Platelet count < 75 x 109/L

               -  Hemoglobin < 9 g/dL

               -  Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 45
                  mL/min

               -  Asymptomatic serum amylase grade > 2 (1.5-2.0 x ULN). Patients with grade 1 or
                  grade 2 serum amylase at the beginning of the study must be confirmed to have no
                  signs or symptoms suggesting pancreatitis or pancreatic injury (e.g., elevated
                  P-amylase, abnormal imaging findings of pancreas, etc.)

               -  Serum lipase > ULN

               -  Potassium, Magnesium, Phosphorus, total Calcium (corrected for serum albumin)
                  outside of normal limits (patients may be enrolled if corrected to within normal
                  limits with supplements during screening)

        Other protocol-defined Exclusion criteria may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with Dose Limiting Toxicities (DLTs)
Time Frame:During the first 2 cycles (42 days) of treatment (Phase Ib)
Safety Issue:
Description:To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D).

Secondary Outcome Measures

Measure:Best overall response (BOR)
Time Frame:From cycle 1, every 6 weeks up to cycle 12, then every 3 cycles until progression of disease per irRC or patient withdrawal, for up to 3 years
Safety Issue:
Description:
Measure:Duration of overall response (DOR)
Time Frame:Baseline, every 6 weeks until progression, for up to 3 years (Phase II)
Safety Issue:
Description:
Measure:Time to response (TTR)
Time Frame:Baseline, every 6 weeks until response (Phase II), for up to 3 years
Safety Issue:
Description:
Measure:Progression-free survival (PFS)
Time Frame:Baseline, every 6 weeks until progression for up to 3 years
Safety Issue:
Description:
Measure:Time to progression (TTP)
Time Frame:Baseline, every 6 weeks until progression for up to 3 years
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:Every 12 weeks until the end of study for up to 3 years
Safety Issue:
Description:
Measure:Overall response rate (ORR)
Time Frame:Baseline, every 6 weeks until progression for up to 3 years (Phase Ib)
Safety Issue:
Description:
Measure:Tiime to progression (TTP)
Time Frame:Baseline, every 6 weeks until progression for up to 3 years
Safety Issue:
Description:
Measure:Pharmacokinetics: Area under the plasma concentration versus time curve (AUC) (INC280)
Time Frame:Day 1 of the first 6 cycles
Safety Issue:
Description:
Measure:PK: Area under the serum concentration versus time curve (AUC) (PDR001)
Time Frame:Days 1, 2, 3, 4, 8, 11 and 15 of Cycles 1 and 3, Day 1 of Cycles 2, 4, 5 and 6
Safety Issue:
Description:
Measure:PK: Plasma concentration vs. time profiles (INC280)
Time Frame:Day 1 of the first 6 cycles
Safety Issue:
Description:
Measure:PK:Serum concentration vs. time profiles (PDR001)
Time Frame:Days 1, 2, 3, 4, 8, 11 and 15 of Cycles 1 and 3, Day 1 of Cycles 2, 4, 5 and 6
Safety Issue:
Description:
Measure:PK: Peak Plasma Concentration (Cmax) (INC280)
Time Frame:Day 1 of the first 6 cycles
Safety Issue:
Description:
Measure:PK:Time of Maximum concentration observed (Tmax) (INC280)
Time Frame:Day 1 of the first 6 cycles
Safety Issue:
Description:
Measure:PK: Peak Serum Concentration (Cmax) (PDR001)
Time Frame:Days 1, 2, 3, 4, 8, 11 and 15 of Cycles 1 and 3, Day 1 of Cycles 2, 4, 5 and 6
Safety Issue:
Description:
Measure:PK: Time of Maximum concentration observed (Tmax) (PDR001)
Time Frame:Days 1, 2, 3, 4, 8, 11 and 15 of Cycles 1 and 3, Day 1 of Cycles 2, 4, 5 and 6
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Phase Ib/II
  • INC280
  • PDR001
  • checkpoint inhibitor
  • PD-1

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