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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02795429
Recruitment Status : Active, not recruiting
First Posted : June 10, 2016
Last Update Posted : January 21, 2020
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Advanced Hepatocellular Carcinoma Drug: PDR001 Drug: INC280 Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : June 15, 2016
Estimated Primary Completion Date : October 20, 2020
Estimated Study Completion Date : October 20, 2020
Arms and Interventions
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Arm Intervention/treatment
Experimental: INC280+PDR001
PDR001 + INC280 treatment in Phase II
 Drug: PDR001
PDR001 will be administered intravenously

Drug: INC280
INC280 will be administered orally
Experimental: PDR001 single agent
PDR001 single agent treatment in Phase II
 Drug: PDR001
PDR001 will be administered intravenously


Outcome Measures
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Primary Outcome Measures :
  1. Number of participants with Dose Limiting Toxicities (DLTs) [ Time Frame: During the first 2 cycles (42 days) of treatment (Phase Ib) ]
    To identify the Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D).

  2. Overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) [ 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 (Phase II) ]

Secondary Outcome Measures :
  1. 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 ]
  2. Duration of overall response (DOR) [ Time Frame: Baseline, every 6 weeks until progression, for up to 3 years (Phase II) ]
  3. Time to response (TTR) [ Time Frame: Baseline, every 6 weeks until response (Phase II), for up to 3 years ]
  4. Progression-free survival (PFS) [ Time Frame: Baseline, every 6 weeks until progression for up to 3 years ]
  5. Time to progression (TTP) [ Time Frame: Baseline, every 6 weeks until progression for up to 3 years ]
  6. Overall survival (OS) [ Time Frame: Every 12 weeks until the end of study for up to 3 years ]
  7. Overall response rate (ORR) [ Time Frame: Baseline, every 6 weeks until progression for up to 3 years (Phase Ib) ]
  8. Tiime to progression (TTP) [ Time Frame: Baseline, every 6 weeks until progression for up to 3 years ]
  9. Pharmacokinetics: Area under the plasma concentration versus time curve (AUC) (INC280) [ Time Frame: Day 1 of the first 6 cycles ]
  10. 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 ]
  11. PK: Plasma concentration vs. time profiles (INC280) [ Time Frame: Day 1 of the first 6 cycles ]
  12. 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 ]
  13. PK: Peak Plasma Concentration (Cmax) (INC280) [ Time Frame: Day 1 of the first 6 cycles ]
  14. PK:Time of Maximum concentration observed (Tmax) (INC280) [ Time Frame: Day 1 of the first 6 cycles ]
  15. 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 ]
  16. 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 ]

Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  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.

Contacts and Locations
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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): NCT02795429


Locations
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United States, Illinois
Novartis Investigative Site
Chicago, Illinois, United States, 60637
Canada, Ontario
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Novartis Investigative Site
Montreal, Quebec, Canada, H3T 1E2
China, Guangdong
Novartis Investigative Site
Guangzhou, Guangdong, China, 510515
China, Shanghai
Novartis Investigative Site
Shanghai, Shanghai, China, 200032
France
Novartis Investigative Site
Montpellier cedex 5, Herault, France, 34059
Novartis Investigative Site
Lille Cedex, France, 59037
Novartis Investigative Site
Toulouse Cedex 9, France, 31059
Germany
Novartis Investigative Site
Heidelberg, Germany, 69120
Novartis Investigative Site
Wuerzburg, Germany, 97080
Hong Kong
Novartis Investigative Site
Hong Kong, Hong Kong
Italy
Novartis Investigative Site
Milano, MI, Italy, 20132
Novartis Investigative Site
Rozzano, MI, Italy, 20089
Novartis Investigative Site
Modena, MO, Italy, 41124
Korea, Republic of
Novartis Investigative Site
Seoul, Korea, Republic of, 03080
Novartis Investigative Site
Seoul, Korea, Republic of, 03722
Taiwan
Novartis Investigative Site
Tainan, Taiwan, 70403
Novartis Investigative Site
Taipei, Taiwan, 10002
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
More Information
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02795429    
Other Study ID Numbers: CINC280X2108
2015-005417-76 ( EudraCT Number )
First Posted: June 10, 2016    Key Record Dates
Last Update Posted: January 21, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

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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 ):
Phase Ib/II
INC280
PDR001
checkpoint inhibitor
PD-1
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