Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Investigate the Pharmacokinetics, Efficacy, and Safety of Atezolizumab Subcutaneous in Patients With Stage IV Non-Small Cell Lung Cancer

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03735121
Recruitment Status : Recruiting
First Posted : November 8, 2018
Last Update Posted : April 10, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE November 7, 2018
First Posted Date  ICMJE November 8, 2018
Last Update Posted Date April 10, 2019
Actual Study Start Date  ICMJE December 27, 2018
Estimated Primary Completion Date April 22, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 7, 2018)
  • Observed Concentration of Atezolizumab in Serum at Cycle 1 in Part 1 [ Time Frame: Predose of Cycle 2. Cycle length is 21 days. ]
  • Observed Concentration of Atezolizumab in Serum at Cycle 1 in Part 2 [ Time Frame: Predose of Cycle 2. Cycle length is 21 days. ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03735121 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 7, 2018)
  • Area Under the Concentration-Time Curve from Time Zero to Infinity (AUC0-inf) of Atezolizumab in Part 1 [ Time Frame: At Cycle 1. Cycle length is 21 days. ]
  • Concentration at the End of a Dosing Interval (Ctrough) of Atezolizumab in Part 1 [ Time Frame: At Cycles 1-3, 7, 11 and 15 and at treatment discontinuation visit. Each cycle is 21 days. ]
  • Maximum Observed Serum Concentration (Cmax) of Atezolizumab in Part 1 [ Time Frame: At Cycles 1-4, 8, 12 and 16. Each cycle is 21 days. ]
  • Time to Maximum Plasma Concentration (Tmax) of Atezolizumab in Part 1 [ Time Frame: At Cycles 1-4, 8, 12 and 16. Each cycle is 21 days. ]
  • Percentage of Participants with Adverse Events in Part 1 and Part 2 [ Time Frame: Up to 4.6 years ]
  • Objective Response Rate (ORR) in Part 2 [ Time Frame: Up to 4.6 years ]
    ORR is defined as the proportion of patients with a partial response (PR) or complete response (CR) as determined by the investigator according to RECIST v1.1.
  • Progression-Free Survival (PFS) in Part 2 [ Time Frame: Up to 4.6 years ]
    PFS is defined as the time from the date of study entry to the date of documented disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever is earlier.
  • Overall Survival (OS) in Part 2 [ Time Frame: Up to 4.6 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Investigate the Pharmacokinetics, Efficacy, and Safety of Atezolizumab Subcutaneous in Patients With Stage IV Non-Small Cell Lung Cancer
Official Title  ICMJE A Two-Part Phase Ib/II Study to Investigate the Pharmacokinetics, Efficacy, and Safety of Atezolizumab Subcutaneous in Patients With Stage IV Non-Small Cell Lung Cancer
Brief Summary This study will evaluate the pharmacokinetics, safety, and efficacy of atezolizumab subcutaneous (SC) in patients with Non-Small Cell Lung Cancer (NSCLC). A dose-finding part (Part 1) will aim to identify the dose of atezolizumab SC that yields drug exposure that is comparable to that of atezolizumab IV. A dose-confirmation part (Part 2) will aim to demonstrate the non inferiority of observed drug exposure following treatment with atezolizumab SC at the identified dose compared with historical drug exposure following treatment with atezolizumab IV.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Sequential Assignment
Intervention Model Description:
Intervention study model can be sequential or in parallel.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-Small Cell Lung Cancer
Intervention  ICMJE
  • Drug: Atezolizumab
    Atezolizumab will be administered as per the schedule specified in arm or cohort.
    Other Name: Tecentriq
  • Drug: Bevacizumab
    Bevacizumab will be administered as per the schedule specified in the arm.
    Other Name: Avastin
  • Drug: Carboplatin
    Carboplatin will be administered as per the schedule specified in the arm.
  • Drug: Paclitaxel
    Paclitaxel will be administered as per the schedule specified in the arm.
  • Drug: rHuPH20
    rHuPH20 will be administered as per the scheduled specified in the cohort for Part 1.
    Other Name: ENHANZE
Study Arms  ICMJE
  • Experimental: Atezolizumab+Bevacizumab+Chemotherapy (Part 2)
    Interventions:
    • Drug: Atezolizumab
    • Drug: Bevacizumab
    • Drug: Carboplatin
    • Drug: Paclitaxel
  • Experimental: Cohort 1: Atezolizumab+rHuPH20 (Part 1)
    Atezolizumab+rHuPH20, followed by Atezolizumab
    Interventions:
    • Drug: Atezolizumab
    • Drug: rHuPH20
  • Experimental: Cohort 2: Atezolizumab+rHuPH20 (Part 1)
    Atezolizumab+rHuPH20, followed by Atezolizumab
    Interventions:
    • Drug: Atezolizumab
    • Drug: rHuPH20
  • Experimental: Cohort 3: Atezolizumab+rHuPH20(Part 1)
    Atezolizumab+rHuPH20, followed by Atezolizumab
    Interventions:
    • Drug: Atezolizumab
    • Drug: rHuPH20
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: November 7, 2018)
245
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 30, 2022
Estimated Primary Completion Date April 22, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically documented locally advanced or metastatic NSCLC
  • Prior platinum-containing regimen or disease recurrence ≤ 6 months since prior platinum-based adjuvant/neoadjuvant regimen.
  • Measurable disease as defined by RECIST v1.1
  • ECOG Performance Status of 0 or 1
  • Life expectancy ≥12 weeks
  • Adequate hematologic and end-organ function

Exclusion Criteria:

  • Symptomatic, untreated, or actively progressing CNS metastases
  • Uncontrolled or symptomatic hypercalcemia
  • Pregnancy or breastfeeding
  • 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
  • Severe infection ≤ 4 weeks
  • Treatment with therapeutic oral or IV antibiotics ≤ 2 weeks prior to study treatment
  • Significant cardiovascular disease
  • Prior allogeneic stem cell or solid organ transplantation
  • Treatment with a live, attenuated vaccine ≤ 4 weeks
  • Treatment with systemic immunostimulatory agents ≤ 4 weeks or 5 half-lives of the drug
  • Treatment with systemic immunosuppressive medication ≤ 2 weeks

Additional Exclusion Criteria (Part 2 Only)

  • No prior anticancer treatment for NSCLC, CD137 agonists or immune checkpoint inhibitors
  • Uncontrolled hypertension, history of hypertensive crisis or hypertensive encephalopathy
  • Significant vascular disease ≤ 6 months
  • History of hemoptysis ≤ 1 month
  • Evidence of active bleeding, bleeding diathesis or coagulopathy
  • Current or recent use of aspirin or with dipyramidole, ticlopidine, clopidogrel, and cilostazol
  • Current use of anticoagulants or thrombolytic agents for therapeutic purposes unstable for > 2 weeks prior to enrollment
  • History of abdominal or tracheosphageal fistula or gastrointestinal perforation ≤ 6 months
  • Clinical signs of gastrointestinal obstruction or requirement for routine treatment
  • Evidence of abdominal free air not explained by paracentesis or recent surgical procedure
  • Serious, non-healing wound, active ulcer, or untreated bone fracture
  • Proteinuria
  • Clear tumor infiltration into the thoracic great vessels or cavitation of pulmonary lesions
  • Grade ≥ 2 peripheral neuropathy
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: BP40657 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 Chile,   France,   Italy,   Korea, Republic of,   Latvia,   New Zealand,   Poland,   Spain,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03735121
Other Study ID Numbers  ICMJE BP40657
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 April 2019

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