Clinical Trial: Phase Ib/II Study of MEDI4736 Evaluated in Different Combinations in Metastatic Pancreatic Ductal Carcinoma

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase Ib and II Open-Label, Multi-Center Study of MEDI4736 Evaluated in Different Combinations in Patients With Metastatic Pancreatic Ductal Adenocarcinoma

Brief Summary: A Phase Ib and II Open-Label, Multi-Center Study of MEDI4736 Evaluated in Different Combinations in Patients with Metastatic Pancreatic Ductal Adenocarcinoma

Detailed Summary: This is a Phase Ib and II open-label, multi-center study to evaluate the safety, tolerability, pharmacodynamics, and antitumor activity of MEDI4736 in combination with chemotherapy and novel anticancer agents in patients with pancreatic ductal adenocarcinoma (PDAC). This study will consist of 2 independent cohorts.
Sponsor: AstraZeneca

Current Primary Outcome:

  • Occurrence of dose-limiting toxicities [ Time Frame: During the first treatment cycle for each patient (28days from 1st dose) ]
    To assess the safety and tolerability of MEDI4736 in combination with chemotherapy agents
  • Objective response rate [ Time Frame: From date of first treatment until confirmed disease progression or death ]
    To assess the efficacy of MEDI4736 in combination with AZD5069 in terms of objective response rate


Original Primary Outcome:

  • Occurrence of dose-limiting toxicities [ Time Frame: During the first treatment cycle for each patient (28days from 1st dose) ]
    To assess the safety and tolerability of MEDI4736 in combination with chemotherapy agents
  • Objective response rate [ Time Frame: From date of first treatment until confirmed disease progression or death for up to 2 year ]
    To assess the efficacy of MEDI4736 in combination with AZD5069 in terms of objective response rate


Current Secondary Outcome:

  • Duration of response [ Time Frame: From date of first treatment until confirmed disease progression or death ]
    To assess the efficacy of MEDI4736 in combination with chemotherapy and AZD5069 and investigate the relationship between PD-L1 expression and efficacy of MEDI4736 in combination with AZD5069
  • Disease control rate [ Time Frame: From date of first treatment until confirmed disease progression or death ]
    To assess the efficacy of MEDI4736 in combination with chemotherapy and AZD5069 and investigate the relationship between PD-L1 expression and efficacy of MEDI4736 in combination with AZD5069
  • Progression-free survival [ Time Frame: From date of first treatment until confirmed disease progression or death ]
    To assess the efficacy of MEDI4736 in combination with chemotherapy and AZD5069 and investigate the relationship between PD-L1 expression and efficacy of MEDI4736 in combination with AZD5069
  • Presence of antidrug antibodies(ADAs) for MEDI4736 [ Time Frame: From baseline until 6 months after last dose ]
    To investigate the immunogenicity of MEDI4736 in combination with AZD5069
  • Pharmacokinetics: Peak concentration (Cmax) [ Time Frame: From baseline to Cycle 7 ]
    To assess the peak concentration of MEDI4736 and the combination of MEDI4736 plus AZD5069, and MEDI4736 plus nab-paclitaxel+ gemcitabine
  • Pharmacokinetics: Trough concentration (Ctrough) [ Time Frame: From baseline to Cycle 7 ]
    Through concentration of MEDI4736 and the combination of MEDI4736 plus AZD5069, and MEDI4736 plus nab-paclitaxel+ gemcitabine
  • DoR, DCR, PFS, PFS3, and PFS6 in all patients using Investigator assessments according to RECIST 1.1, OS, OS6 and OS12 [ Time Frame: From date of first treatment until progression or death ]
    To further assess the efficacy of MEDI4736 and AZD5069 in terms of DoR, DCR, PFS, PFS3, PFS6, OS, OS6 and OS12
  • Presense of ADA's for MEDI4736 (Confirmatory Results: Positive or negative; tiers) [ Time Frame: From data of first treatment until confirmed disease progression or death ]
    To investigate the immunogenicity of MEDI4736 in combination with AZD5069
  • Concentration of MEDI4736/ AZD5069 in blood and noncomparemental PK parameters (such as peak concentration and trough, as data allow, sparse sampling) [ Time Frame: From date of first treatment until confirmed progression or death ]
    To assess the PK of MEDI4736 and the combination of MEDI4736 and AZD5069
  • Objective Response Rate [ Time Frame: From date of first treatment until confirmed diseases progression or death ]
    To assess the efficacy of MEDI4736 in combination with chemotherapy and AZD5069 and investigate the relationship between PD-L1 expression and efficacy of MEDI4736 in combination with AZD5069
  • Overall Surival [ Time Frame: From date of first treatment until death ]
    To assess the efficacy of MEDI4736 in combination with chemotherapy and AZD5069 and investigate the relationship between PD-L1 expression and efficacy of MEDI4736 in combination with AZD5069
  • Number of subjects with Adverse Events as a measure of safety and tolerability of AZD5069 in combination with MEDI4736 [ Time Frame: From baseline and throughout treatment up until 3 months after last dose ]
    To assess the safety and tolerability profile of AZD5069 in combination with MEDI4736; vital signs (blood pressure, pulse, weight); laboratory parameters (clinical chemistry, haematology, urinalysis); physical examination; electrocardiograms (ECGs)


Original Secondary Outcome:

  • Duration of response [ Time Frame: From date of first treatment until confirmed disease progression or death for up to 2 years ]
    To assess the efficacy of MEDI4736 in combination with chemotherapy and AZD5069, and to investigate the relationship between PD-L1 expression
  • Disease control rate [ Time Frame: From date of first treatment until confirmed disease progression or death for up to 2 years ]
    To assess the efficacy of MEDI4736 in combination with chemotherapy and AZD5069, and to investigate the relationship between PD-L1 expression
  • Progression-free survival [ Time Frame: From date of first treatment until confirmed disease progression or death for up to 2 years ]
    To assess the efficacy of MEDI4736 in combination with chemotherapy and AZD5069, and to investigate the relationship between PD-L1 expression
  • Presence of antidrug antibodies(ADAs) for MEDI4736 [ Time Frame: Up to 1 year ]
    To investigate the immunogenicity of MEDI4736 in combination with chemotherapy and AZD5069
  • Pharmacokinetics of MEDI4736: Peak concentration (Cmax) [ Time Frame: Up to 1 year ]
    Peak concentration in MEDI4736 +chemotherapy or MEDI4736+AZD5069
  • Pharmacokinetics of MEDI4736: Trough concentration (Ctrough) [ Time Frame: Up to 1 year ]
    Through concentration in MEDI4736 +chemotherapy or MEDI4736+AZD5069


Information By: AstraZeneca

Dates:
Date Received: October 20, 2015
Date Started: March 25, 2016
Date Completion: February 14, 2018
Last Updated: March 2, 2017
Last Verified: March 2017