Clinical Trials /

Safety and Efficacy Study of PDR001 in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma

NCT02605967

Description:

The purpose of this randomized controlled Phase II study is to assess the efficacy of PDR001 versus investigator's choice of chemotherapy in patients with advanced NPC. By blocking the interaction between PD-1 and its ligands PD-L1 and PD-L2, PDR001 leads to the activation of a T cell mediated antitumor immune response

Related Conditions:
  • Nasopharyngeal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy Study of PDR001 in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma
  • Official Title: A Phase II, Open-label, Randomized Controlled Study of PDR001 in Patients With Moderately Differentiated/Undifferentiated Locally Advanced Recurrent or Metastatic Nasopharyngeal Carcinoma Who Progressed on Standard Treatment

Clinical Trial IDs

  • ORG STUDY ID: CPDR001X2201
  • NCT ID: NCT02605967

Conditions

  • Nasopharyngeal Carcinoma

Interventions

DrugSynonymsArms
PDR001PDR001 - Investigational drug
Investigator choice of chemotherapyChemotherapy

Purpose

The purpose of this randomized controlled Phase II study is to assess the efficacy of PDR001 versus investigator's choice of chemotherapy in patients with advanced NPC. By blocking the interaction between PD-1 and its ligands PD-L1 and PD-L2, PDR001 leads to the activation of a T cell mediated antitumor immune response

Trial Arms

NameTypeDescriptionInterventions
PDR001 - Investigational drugExperimentalanti-PD1 humanized monoclonal antibody
  • PDR001
ChemotherapyActive Comparatorcommonly used chemotherapy as per investigator's choice
  • Investigator choice of chemotherapy

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically documented non-keratinizing locally advanced recurrent or metastatic
             NPC.

          -  Must be resistant to platinum-based chemotherapy (defined as progression on or after
             platinum-based chemotherapy given in the recurrent/metastatic setting).

          -  May have received at least 1 prior therapy for recurrent or metastatic disease, up to
             2 prior systemic therapies.

          -  An archival tumor specimen or newly obtained tumor sample may be submitted at
             screening/baseline (a fresh tumor sample is preferred), unless agreed differently
             between Novartis and the Investigator.

          -  At least 1 measurable lesion (as per RECIST v1.1) progressing or new since last
             anti-tumor therapy.

          -  Prior treated brain or meningeal metastases must be without MRI evidence of
             progression for at least 8 weeks and off systemic steroids for at least 2 weeks prior
             to screening/baseline.

          -  Patient must be willing to undergo testing for human immunodeficiency virus (HIV) if
             not tested within the past 6 months. If HIV+ positive, patient will be eligible if:
             his/ her CD4+ count ≥ 300/μL; his/her viral load is undetectable; he/she is currently
             receiving highly active antiretroviral therapy (HAART).

        Exclusion Criteria:

          -  History of severe hypersensitivity reactions to other mAbs

          -  Active autoimmune disease or a documented history of autoimmune disease, except
             vitiligo or resolved asthma/atopy that is treated with broncho-dilators.

          -  Active HBV or HCV infections requiring therapy.

          -  Prior PD-1- or PD-L1-directed therapy or any therapeutic cancer vaccine.

          -  Patients receiving systemic treatment with any immunosuppressive medication.

          -  Use of any vaccines against infectious diseases (e.g. varicella, pneumococcus) within
             4 weeks of initiation of study treatment.

        Other protocol-define inclusion/exclusion may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival
Time Frame:approximately 20 months after FPFV
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:2 years
Safety Issue:
Description:evaluate the anti-tumor activity of PDR001 versus investigator choice of chemotherapy in NPC patients
Measure:Composite serum pharmacokinetics (PK) parameters
Time Frame:1 year
Safety Issue:
Description:characterize the pharmacokinetics profiles of PDR001; PK parameters area under the curve (AUC)
Measure:Presence and /or concentration of anti-PDR001 antibodies
Time Frame:1 year
Safety Issue:
Description:Assess immunogenicity serum concentration
Measure:Overall response rate (ORR)
Time Frame:1 year
Safety Issue:
Description:evaluate the anti-tumor activity of PDR001 versus investigator choice of chemotherapy in NPC patients
Measure:Duration of response (DOR)
Time Frame:1 year
Safety Issue:
Description:evaluate the anti-tumor activity of PDR001 versus investigator choice of chemotherapy in NPC patients
Measure:Time to progression (TTP)
Time Frame:1 year
Safety Issue:
Description:evaluate the anti-tumor activity of PDR001 versus investigator choice of chemotherapy in NPC patients
Measure:immune related progression free survival (irPFS) using central assessment
Time Frame:2 years
Safety Issue:
Description:evaluate the anti-tumor activity of PDR001 versus investigator choice of chemotherapy in NPC patients
Measure:serum concentration vs.time profiles
Time Frame:1 year
Safety Issue:
Description:serum concentration of PDR001 on D1,D8,D15,D29,D36,D43,D57,D58,D64,D71,D85,D140
Measure:Potential associations between expression of PD-L1, CD8 and other immunological markers with anti-tumor activity
Time Frame:2 years
Safety Issue:
Description:assess changes in expression of immunological markers such as CD8 and PD-L1 in tumor biopsies
Measure:expression of immune-related genes (RNA/protein in tumor sample
Time Frame:2 years
Safety Issue:
Description:assess changes in immune-related gene signature
Measure:Peripheral, soluble ligands and cytokine levels
Time Frame:2 years
Safety Issue:
Description:assess plasma concentration levels of cytokines interferon-gamma ( IFN-γ) in pg/ml
Measure:Composite serum pharmacokinetics (PK) parameters
Time Frame:1 year
Safety Issue:
Description:characterize the pharmacokinetics profiles of PDR001; PK parameters maximum plasma concentration(Cmax)
Measure:Composite serum pharmacokinetics (PK) parameters
Time Frame:1 year
Safety Issue:
Description:characterize the pharmacokinetics profiles of PDR001; PK parameter as the time to reach maximum peak plasma (Tmax)
Measure:Composite serum pharmacokinetics (PK) parameters
Time Frame:1 year
Safety Issue:
Description:characterize the pharmacokinetics profiles of PDR001; PK parameters include the elimination half-life (T1/2)
Measure:Peripheral, soluble ligands and cytokine levels
Time Frame:2 years
Safety Issue:
Description:assess plasma concentration levels of cytokines as tumor necrosis factor-alpha (TNF-α) in pg/ml
Measure:Peripheral, soluble ligands and cytokine levels
Time Frame:2 years
Safety Issue:
Description:assess plasma concentration levels of cytokines as Interleukin-6 ( IL-6) in pg/ml

Details

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

Trial Keywords

  • PDR001,
  • nasopharyngeal cancer,
  • moderately differentiated/undifferentiated,
  • locally advanced,
  • recurrent or metastatic NPC,
  • after first- line platinum-based therapy

Last Updated

March 17, 2017