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A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer)

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ClinicalTrials.gov Identifier: NCT03193190
Recruitment Status : Recruiting
First Posted : June 20, 2017
Last Update Posted : December 6, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE June 9, 2017
First Posted Date  ICMJE June 20, 2017
Last Update Posted Date December 6, 2019
Actual Study Start Date  ICMJE July 5, 2017
Estimated Primary Completion Date February 15, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 16, 2017)
  • Percentage of Participants With Objective Response, as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) [ Time Frame: From randomization until disease progression or loss of clinical benefit (up to approximately 3-5 years) ]
  • Percentage of Participants With Adverse Events (AEs) [ Time Frame: From first study treatment administration until 30 days after the last dose or until initiation of new systemic anti-cancer therapy, whichever occurs first (up to approximately 3-5 years) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03193190 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 29, 2018)
  • Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1 [ Time Frame: From randomization up to the first occurrence of disease (up to approximately 3-5 years) ]
  • Overall Survival [ Time Frame: From randomization up to death from any cause (up to approximately 3-5 years) ]
  • Percentage of Participants who are Alive at Month 6 [ Time Frame: Month 6 ]
  • Duration of Response, as Determined by Investigator According to RECIST v1.1 [ Time Frame: From the date of first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 3-5 years) ]
  • Percentage of Participants With Disease Control, as Determined by Investigator According to RECIST v1.1 [ Time Frame: From randomization until disease progression or loss of clinical benefit (up to approximately 3-5 years) ]
  • Serum Concentration of Atezolizumab [ Time Frame: Pre-infusion (0 hour [hr]) on Day 1 of Cycle 1 up to 30 days and 120 days after last dose (up to approximately 3-5 years)(Detailed timeframe is provided in outcome measure description) ]
    Pre-infusion (0 hour [hr]), 30 minutes (min) post-infusion (infusion duration=60 min) on Day 1 of Cycle 1; pre-infusion (0 hr) on Day 1 of Cycles 2, 3, 4, 8, 12, 16 (21 or 28 day cycles); 30 days and 120 days after last dose (up to approximately 3-5 years)
  • Plasma Concentration of Cobimetinib [ Time Frame: Pre-dose (0 hr) and 2-4 hrs post-dose on Day 15 of Cycle 1 (cycle length=28 days)(up to approximately 3-5 years). ]
  • Plasma Concentration of PEGPH20 [ Time Frame: Pre-infusion (0 hr) on Day 1 of Cycle 1 up to 30 days and 120 days after last dose (up to approximately 3-5 years) (Detailed timeframe is provided in outcome measure description) ]
    Pre-infusion (0 hr), 5 min and 1-3 hrs post infusion (infusion duration=10-12 min) on Day 1 of Cycle 1; pre-infusion (0 hr) on Days 8 and 15 of Cycle 1, and Day 1 of Cycles 3, 4, 8, 12, 16; pre-infusion (0 hr) and 5 min post-infusion on Day 1 of Cycle 2 (each cycle=21 days); 30 days and 120 days after last dose (up to approximately 3-5 years)
  • Plasma Concentration of BL-8040 [ Time Frame: Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Day 1 of Cycle 1) up to 30 days after last dose (up to approximately 3-5 years) (Detailed timeframe is provided in outcome measure description) ]
    Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Day 1 of Cycle 1); 1 hr post-dose on Days 1, 5 of priming period; pre-dose (0 hr), 1 hour post-dose on Day 15 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 8, 12, 16; pre-dose (0 hr) on Day 1 of Cycle 20 and every 4 cycles thereafter (each cycle=21 days); 30 days after last dose (up to approximately 3-5 years).
  • Percentage of Participants With Anti-Drug Antibody (ADA) to Atezolizumab [ Time Frame: Pre-infusion (0 hr) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 (21 or 28 day cycles); 30 days and 120 days after last dose (up to approximately 3-5 years) ]
  • Percentage of Participants With ADA to PEGPH20 [ Time Frame: Pre-infusion (0 hr) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 (each cycle=21 days); 30 days and 120 days after last dose (up to approximately 3-5 years) ]
  • Percentage of Participants With ADA to BL-8040 [ Time Frame: Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Day 1 of Cycle 1) up to 30 days after last dose (up to approximately 3-5 years) (Detailed timeframe is provided in outcome measure description) ]
    Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Cycle 1 Day 1), Day 15 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 8, 12, 16, 20 and every 4 cycles thereafter (each cycle=21 days) (up to approximately 3-5 years); 30 days after last dose (up to approximately 3-5 years)
  • Serum Concentration of RO6874281 [ Time Frame: Pre-infusion (0 hr) on Day 1 of Cycle 1 up to 30 days after last dose (up to approximately 3-5 years) (Detailed timeframe is provided in outcome measure description) ]
    For RO6874281 Q2W: Pre-infusion (0 hour [hr]), at end of infusion, and 4 hours after infusion on Day 1 of Cycle 1; pre-infusion (0 hr) and at end of infusion on Day 15 of Cycle 1; pre-infusion (0 hr) and at end of infusion on day 1 of Cycles 2, 3, 4, 6, 8, 10, 12, 15 and 18 and every third cycle thereafter (each cycle=28 days); and 30 days after last dose (up to approximately 3-5 years). For RO6874281 Q3W: Pre-infusion (0 hour [hr]), at end of infusion, 2 hours after infusion and 4 hours after infusion on Day 1 of Cycles 1 and 3; 24 hours after the Day 1 infusion for Cycles 1 and 3; 48 hours after the Day 1 infusion for Cycles 1 and 3; 168 hours after the Day 1 infusion for Cycles 1 and 3; 1 hour after initiation of infusion on Day 1 of Cycle 1; pre-infusion (0 hr) and at end of infusion on day 1 of Cycles 2, 4, 6, 8, 10, 12, 14, 16 and 19 and every third cycle thereafter (each cycle=21 days); and 30 days after last dose (up to approximately 3-5 years).
  • Serum Concentration of Emactuzumab [ Time Frame: Pre-dose (0 hour [hr]) on Day 1 of Cycle 1 up to 30 days after last dose (up to approximately 3-5 years)(Detailed timeframe is provided in outcome measure description) ]
    Cohort 1: Pre-dose (0 hour [hr]) on Day 1 and 8 of Cycle 1; pre-dose (0 hr) and at end of Emactuzumab infusion on day 1 of Cycles 2, 3, 4, 8, 12 and 16 (each cycle = 28 days); and 30 days after last dose (up to approximately 3-5 years). Cohort 2: Pre-dose (0 hour [hr]) on Day 1 of Cycle 1; on Day 15 of Cycle 1; pre-dose (0 hr) and at end of Emactuzumab infusion on day 1 of Cycles 2, 3, 4, 8, 12 and 16 (each cycle = 21 days); and 30 days after last dose (up to approximately 3-5 years).
  • Serum Concentration of Selicrelumab [ Time Frame: Pre-dose (0 hour [hr]) on Days 1 and 8 of Cycle 1, 4, 8, 12 and 16; pre-dose (0 hr) on day 1 of Cycle 2 (each cycle = 28 days); and 30 days after last dose (up to approximately 3-5 years). ]
  • Serum Concentration of Bevacizumab [ Time Frame: Pre-dose (0 hour [hr]) on Days 1 of Cycle 1 and 4 (each cycle = 28 days); and 30 days after last dose (up to approximately 3-5 years). ]
  • Percentage of Participants With ADA to RO6874281 [ Time Frame: Pre-infusion (0 hr) on Day 1 of Cycle 1 up to 30 days after last dose (up to approximately 3-5 years) (Detailed timeframe is provided in outcome measure description). ]
    RO6874281 Q2W arm: Pre-infusion (0 hour [hr]) on Days 1 and 15 of Cycle 1; pre-infusion (0 hour [hr]) on Day 1 of Cycles 2, 3, 4, 6, 8, 10, 12, 15 and 18 and every third cycle thereafter (each cycle=28 days); and 30 days after last dose (up to approximately 3-5 years). RO6874281 Q3W arm: Pre-infusion (0 hour [hr]) on Day 1 of cycles 1, 2, 3, 4, 6, 8, 10, 12, 14, 16 and 19 and every third cycle thereafter (each cycle=21 days); and 30 days after last dose (up to approximately 3-5 years).
  • Percentage of Participants With ADA to Emactuzumab [ Time Frame: Pre-dose (0 hour [hr]) on Day 1 up to 30 days after last dose (up to approximately 3-5 years)(Detailed timeframe is provided in outcome measure description). ]
    Cohort 1: Pre-dose (0 hour [hr]) on Day 1 and 8 of Cycle 1; pre-dose (0 hr) on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (each cycle = 28 days); and 30 days after last dose (up to approximately 3-5 years). Cohort 2: Pre-dose (0 hour [hr]) on Day 1 of Cycle 1; on Day 15 of Cycle 1; pre-dose (0 hr) on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (each cycle = 21 days); and 30 days after last dose (up to approximately 3-5 years).
  • Percentage of Participants With ADA to Selicrelumab [ Time Frame: Pre-dose (0 hour [hr]) on Day 1 of cycles 1, 2, 4, 8, 12 and 16 (each cycle = 28 days); and 30 days after last dose (up to approximately 3-5 years). ]
  • Percentage of Participants With ADA to Bevacizumab [ Time Frame: Pre-dose (0 hour [hr]) on Day 1 of Cycles 1 and 4 (each cycle = 28 days); and 30 days after last dose (up to approximately 3-5 years). ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2017)
  • Progression-Free Survival (PFS), as Determined by Investigator According to RECIST v1.1 [ Time Frame: From randomization up to the first occurrence of disease (up to approximately 3-5 years) ]
  • Overall Survival [ Time Frame: From randomization up to death from any cause (up to approximately 3-5 years) ]
  • Percentage of Participants who are Alive at Month 6 [ Time Frame: Month 6 ]
  • Duration of Response, as Determined by Investigator According to RECIST v1.1 [ Time Frame: From the date of first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 3-5 years) ]
  • Percentage of Participants With Disease Control, as Determined by Investigator According to RECIST v1.1 [ Time Frame: From randomization until disease progression or loss of clinical benefit (up to approximately 3-5 years) ]
  • Serum Concentration of Atezolizumab [ Time Frame: Pre-infusion (0 hour [hr]), 30 minutes (min) post-infusion (infusion duration=60 min) on Day 1 of Cycle 1; pre-infusion (0 hr) on Day 1 of Cycles 2, 3, 4, 8, 12, 16 (each cycle=28 days); 30 days and 120 days after last dose(up to approximately 3-5 years) ]
  • Plasma Concentration of Cobimetinib [ Time Frame: Pre-dose (0 hr) and 2-4 hrs post-dose on Day 15 of Cycle 1 (cycle length=28 days) ]
  • Plasma Concentration of PEGPH20 [ Time Frame: Pre-infusion (0 hr) on Day 1 of Cycle 1 up to 30 days and 120 days after last dose (up to approximately 3-5 years) (Detailed timeframe is provided in outcome measure description) ]
    Pre-infusion (0 hr), 5 min and 1-3 hrs post infusion (infusion duration=10-12 min) on Day 1 of Cycle 1; pre-infusion (0 hr) on Days 8 and 15 of Cycle 1, Day 1 of Cycles 3, 4, 8, 12, 16; pre-infusion (0 hr) and 5 min post-infusion on Day 1 of Cycle 2 (each cycle=21 days); 30 days and 120 days after last dose (up to approximately 3-5 years)
  • Plasma Concentration of BL-8040 [ Time Frame: Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Day 1 of Cycle 1) up to 30 days after last dose (up to approximately 3-5 years) (Detailed timeframe is provided in outcome measure description) ]
    Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Day 1 of Cycle 1); 1 hr post-dose on Days 1, 5 of priming period; pre-dose (0 hr), 1 hour post-dose on Day 15 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 8, 12, 16; pre-dose (0 hr) on Day 1 of Cycle 20 and every 4 cycles thereafter (each cycle=21 days) (up to approximately 3-5 years); 30 days after last dose (up to approximately 3-5 years)
  • Percentage of Participants With Anti-Drug Antibody (ADA) to Atezolizumab [ Time Frame: Pre-infusion (0 hr) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 (each cycle=28 days); 30 days and 120 days after last dose (up to approximately 3-5 years) ]
  • Percentage of Participants With ADA to PEGPH20 [ Time Frame: Pre-infusion (0 hr) on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 (each cycle=21 days); 30 days and 120 days after last dose (up to approximately 3-5 years) ]
  • Percentage of Participants With ADA to BL-8040 [ Time Frame: Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Day 1 of Cycle 1) up to 30 days after last dose (up to approximately 3-5 years) (Detailed timeframe is provided in outcome measure description) ]
    Pre-dose (0 hr) on Day 1 of priming period (1 week prior to Cycle 1 Day 1), Day 15 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 8, 12, 16, 20 and every 4 cycles thereafter (each cycle=21 days) (up to approximately 3-5 years); 30 days after last dose (up to approximately 3-5 years)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Multiple Immunotherapy-Based Treatment Combinations in Participants With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer)
Official Title  ICMJE A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic Pancreatic Ductal Adenocarcinoma (Morpheus-Pancreatic Cancer)
Brief Summary

A Phase Ib/II, open-label, multicenter, randomized study designed to assess the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of immunotherapy-based treatment combinations in participants with metastatic Pancreatic Ductal Adenocarcinoma (PDAC).

Two cohorts will be enrolled in parallel in this study: Cohort 1 will consist of patients who have received no prior systemic therapy for metastatic PDAC, and Cohort 2 will consist of patients who have received one line of prior systemic therapy for PDAC. In each cohort, eligible patients will be assigned to one of several treatment arms.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pancreatic Adenocarcinoma
Intervention  ICMJE
  • Drug: Nab-Paclitaxel
    Nab-Paclitaxel will be administered as per the schedule specified in the respective arm.
  • Drug: Gemcitabine
    Gemcitabine will be administered as per the schedule specified in the respective arm.
  • Drug: Oxaliplatin
    Oxaliplatin will be administered as per the schedule specified in the respective arm.
  • Drug: Leucovorin
    Leucovorin will be administered as per the schedule specified in the respective arm.
  • Drug: Fluorouracil
    Fluorouracil will be administered as per the schedule specified in the respective arm.
  • Drug: Atezolizumab
    Atezolizumab will be administered as per the schedule specified in the respective arm.
  • Drug: Cobimetinib
    Cobimetinib will be administered as per the schedule specified in the respective arm.
  • Drug: PEGPH20
    PEGPH20 will be administered as per the schedule specified in the respective arm.
  • Drug: BL-8040
    BL-8040 will be administered as per the schedule specified in the respective arm.
  • Drug: Selicrelumab
    Selicrelumab will be administered as per the schedule specified in the respective arm.
  • Drug: Bevacizumab
    Bevacizumab will be administered as per the schedule specified in the respective arm.
  • Drug: Emactuzumab
    Emactuzumab will be administered as per the schedule specified in the respective arm.
  • Drug: RO6874281
    RO6874281 will be administered as per the schedule specified in the respective arm
Study Arms  ICMJE
  • Active Comparator: Cohort 1: Control (Nab-Paclitaxel and Gemcitabine)

    Cohort 1: Participants will receive Nab-Paclitaxel 125 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; and Gemcitabine 1000 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle.

    Participants in the Cohort 1 control arm who experience disease progression will be given the option of enrolling into Cohort 2 (if open for enrollment), provided they meet eligibility criteria.

    Interventions:
    • Drug: Nab-Paclitaxel
    • Drug: Gemcitabine
  • Experimental: Cohort 1: Atezolizumab + Chemotherapy + Selicrelumab
    Cohort 1: Participants will receive Atezolizumab 840 mg IV infusion on Days 1 and 15 of each 28 day cycle; Nab-paclitaxel 125 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; Gemcitabine 1000 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; and Selicrelumab 16 mg subcutaneous injection on Day 1 of Cycles 1−4 and every third cycle thereafter (i.e. Cycles 7, 10, 13 etc.) of each 28-day cycle.
    Interventions:
    • Drug: Nab-Paclitaxel
    • Drug: Gemcitabine
    • Drug: Atezolizumab
    • Drug: Selicrelumab
  • Experimental: Cohort 1: Atezolizumab + Chemo + Selicrelumab + Bevacizumab
    Cohort 1: Participants will receive Atezolizumab 840 mg IV infusion on Days 1 and 15 of each 28 day cycle; Bevacizumab 10 mg/kg IV infusion on Days 1 and 15 of each 28 day cycle; Nab-paclitaxel 125 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; Gemcitabine 1000 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; and Selicrelumab 16 mg subcutaneous on Day 1 of Cycles 1−4 and every third cycle thereafter (i.e. Cycles 7, 10, 13 etc.) of each 28-day cycle.
    Interventions:
    • Drug: Nab-Paclitaxel
    • Drug: Gemcitabine
    • Drug: Atezolizumab
    • Drug: Selicrelumab
    • Drug: Bevacizumab
  • Experimental: Cohort 1: Atezolizumab + Chemotherapy + Bevacizumab
    Cohort 1: Participants will receive Atezolizumab 840 mg IV infusion on Days 1 and 15 of each 28 day cycle; Bevacizumab 10 mg/kg IV infusion on Days 1 and 15 of each 28 day cycle; Nab-paclitaxel 125 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; Gemcitabine 1000 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle.
    Interventions:
    • Drug: Nab-Paclitaxel
    • Drug: Gemcitabine
    • Drug: Atezolizumab
    • Drug: Bevacizumab
  • Experimental: Cohort 1: Atezolizumab + Chemotherapy + Emactuzumab
    Cohort 1: Participants will receive Emactuzumab 1000 mg IV infusion on Days 1 and 15 of each 28 day cycle; Atezolizumab 840 mg IV infusion on Days 1 and 15 of each 28 day cycle; Nab-paclitaxel 125 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; Gemcitabine 1000 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle.
    Interventions:
    • Drug: Nab-Paclitaxel
    • Drug: Gemcitabine
    • Drug: Atezolizumab
    • Drug: Emactuzumab
  • Experimental: Cohort 2: Atezolizumab + Cobimetinib

    Cohort 2: Participants will receive Cobimetinib 60 milligrams (mg) once daily orally on Days 1-21 of each 28-day cycle; and Atezolizumab 840 mg IV infusion on Days 1 and 15 of each 28-day cycle.

    Participants who progressed on treatment may have the option of receiving Atezolizumab + RO6874281 treatment, provided they meet the eligibility criteria and the arm is open for enrollment.

    Interventions:
    • Drug: Atezolizumab
    • Drug: Cobimetinib
  • Experimental: Cohort 2: Atezolizumab + PEGPH20

    Cohort 2: Participants will receive PEGPH20 3 micrograms per kilogram (mcg/kg) IV infusion on Days 1, 8 and 15 of each 21-day cycle; and Atezolizumab 1200 mg IV infusion on Day 1 of each 21-day cycle.

    Participants who progressed on treatment, may have the option of receiving Atezolizumab + Cobimetinib or Atezolizumab + RO6874281 treatment, provided they meet the eligibility criteria and the arms are open for enrollment.

    Interventions:
    • Drug: Atezolizumab
    • Drug: PEGPH20
  • Experimental: Cohort 2: Atezolizumab + BL-8040

    Cohort 2: Participants will receive BL-8040 1.25 milligrams per kilogram (mg/kg) subcutaneously (SC) on Days 1-5 of the first week, followed by combination treatment consisting of BL-8040 1.25 mg/kg SC three times a week on non-consecutive days and Atezolizumab 1200 mg IV infusion on Day 1 of each 21-day cycle.

    Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib or Atezolizumab + RO6874281 treatment, provided they meet the eligibility criteria and the arms are open for enrollment.

    Interventions:
    • Drug: Atezolizumab
    • Drug: BL-8040
  • Experimental: Cohort 2: Atezolizumab + RO6874281 every 2 weeks

    Cohort 2: Participants will receive Atezolizumab 840 mg IV infusion on days 1 and 15 of each 28 day cycle; RO6874281 will be administered 10 mg by IV infusion on day 1 and 15 mg on days 8, 15, and 22 for cycle 1 (28 day cycle). RO6874281 will be administered 15 mg by IV infusion on days 1 and 15 of each subsequent 28 day cycle.

    Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib, provided they meet the eligibility criteria and the arm is open for enrollment.

    Interventions:
    • Drug: Atezolizumab
    • Drug: RO6874281
  • Experimental: Cohort 2: Atezolizumab + RO6874281 every 3 weeks

    Cohort 2: Participants will receive Atezolizumab 1200 mg IV infusion on Day 1 of each 21 day cycle; and RO6874281 10 mg by IV infusion on day 1 of each 21 day cycle.

    Participants who progressed on treatment may have the option of receiving Atezolizumab + Cobimetinib, provided they meet the eligibility criteria and the arm is open for enrollment.

    Interventions:
    • Drug: Atezolizumab
    • Drug: RO6874281
  • Experimental: Cohort 2: Atezolizumab + Emactuzumab

    Cohort 2: Participants will receive Emactuzumab 1000 mg IV infusion on day 1 of each 21 day cycle; and Atezolizumab 1200 mg IV infusion on Day 1 of each 21 day cycle.

    Participants who progressed on treatment, may have the option of receiving Atezolizumab + Cobimetinib or Atezolizumab + RO6874281 treatment, provided they meet the eligibility criteria and the arms are open for enrollment.

    Interventions:
    • Drug: Atezolizumab
    • Drug: Emactuzumab
  • Active Comparator: Cohort 2: Control (Nab-Paclitaxel and Gemcitabine or mFOLFOX6)

    Cohort 2: Participants who progressed on a prior fluoropyrimidine-based regimen will receive Nab-paclitaxel 125 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle; and Gemcitabine 1000 mg/m2 IV infusion on Days 1, 8, and 15 of each 28 day cycle.

    Participants who progressed on a prior gemcitabine-based regimen will receive 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6). Participants will receive Oxaliplatin 85 mg/m2 IV on Days 1 and 15 of each 28 day cycle; Leucovorin 400 mg/m2 IV on Days 1 and 15 of each 28 day cycle; Fluorouracil 400 mg/m2 IV push on Days 1 and 15 of each 28 day cycle; and Fluorouracil 2400 mg/m2 IV continuous infusion over 46 hours on Days 1 and 2 and on Days 15 and 16 of each 28 day cycle.

    Participants who progressed on treatment, may have the option of receiving Atezolizumab + Cobimetinib or Atezolizumab + RO6874281 treatment, provided they meet the eligibility criteria and the arms are open for enrollment.

    Interventions:
    • Drug: Nab-Paclitaxel
    • Drug: Gemcitabine
    • Drug: Oxaliplatin
    • Drug: Leucovorin
    • Drug: Fluorouracil
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 29, 2018)
205
Original Estimated Enrollment  ICMJE
 (submitted: June 16, 2017)
185
Estimated Study Completion Date  ICMJE February 15, 2022
Estimated Primary Completion Date February 15, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma
  • For patients in Cohort 1: no prior systemic treatment for PDAC
  • For patients in Cohort 2: disease progression during administration of either 5-FU− or gemcitabine-based first-line chemotherapy
  • Life expectancy greater than or equal to 3 months
  • Availability of a representative tumor specimen that is suitable for determination of programmed death-ligand 1 (PD-L1) and/or additional biomarker status via central testing
  • Measurable disease (at least one target lesion) according to RECIST v1.1
  • Adequate hematologic and end-organ function test results
  • Tumor accessible for biopsy
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating eggs, as outlined for each specific treatment arm
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm

Exclusion Criteria:

  • Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
  • History of leptomeningeal disease
  • Active or history of autoimmune disease or immune deficiency
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Positive human immunodeficiency (HIV) test at screening or at any time prior to screening
  • Active hepatitis B or C virus infection or active tuberculosis
  • Severe infection within 4 weeks prior to initiation of study treatment
  • Prior allogeneic stem cell or solid organ transplantation
  • History of malignancy other than pancreatic carcinoma within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Reference Study ID Number: WO39608 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com
Listed Location Countries  ICMJE Germany,   Korea, Republic of,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03193190
Other Study ID Numbers  ICMJE WO39608
2016-004126-42 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP