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A Study of Atezolizumab (an Engineered Anti-Programmed Death-Ligand 1 [PDL1] Antibody) to Evaluate Safety, Tolerability and Pharmacokinetics in Participants With Locally Advanced or Metastatic Solid Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01375842
First received: June 16, 2011
Last updated: August 1, 2017
Last verified: August 2017
June 16, 2011
August 1, 2017
June 21, 2011
May 7, 2018   (Final data collection date for primary outcome measure)
  • Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Day 1 up to Day 21 ]
  • Maximum Tolerated Dose (MTD) of Atezolizumab [ Time Frame: Day 1 up to Day 21 ]
  • Recommended Phase 2 Dose (RP2D) of Atezolizumab [ Time Frame: Baseline up to time of determination of MTD (up to Day 21) ]
  • Percentage of Participants With Adverse Events [ Time Frame: Baseline up to 90 days after the last dose of study treatment or until initiation of another anti-cancer therapy, whichever occurs first (up to approximately [approx] 7 years [yrs]) ]
  • Incidence of dose limiting toxicities (DLTs) [ Time Frame: Up to day 21 ]
  • Nature of dose limiting toxicities (DLTs) [ Time Frame: Up to day 21 ]
Complete list of historical versions of study NCT01375842 on ClinicalTrials.gov Archive Site
  • Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) [ Time Frame: Predose(0 hour[hr])on Day 1 of Cycles 1,2,4,8,16,17,20(Cycle length=21 days), every 8 cycles thereafter, at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure(up to approx 7 yrs) ]
  • Area Under the Concentration-Time Curve (AUC) of Atezolizumab [ Time Frame: Predose (0 hr) on Day 1 of Cycle 1 up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) (Detailed timeframe provided in outcome measure description) ]
    Dose-Escalation Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 minutes [min]) on Day 1 of Cycles 1-5, 7 (Cycle length=21 days); Days 2, 4, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 8, 10, 12, 14, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) Expansion Cohort: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 min) on Day 1 of Cycles 1-4 (Cycle length=21 days); Days 2, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 2-5, 7, 8, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs)
  • Maximum Serum Concentration (Cmax) of Atezolizumab [ Time Frame: Predose (0 hr) on Day 1 of Cycle 1 up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) (Detailed timeframe provided in outcome measure description) ]
    Dose-Escalation Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 minutes [min]) on Day 1 of Cycles 1-5, 7 (Cycle length=21 days); Days 2, 4, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 8, 10, 12, 14, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) Expansion Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 min) on Day 1 of Cycles 1-4 (Cycle length=21 days); Days 2, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 2-5, 7, 8, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs)
  • Minimum Serum Concentration (Cmin) of Atezolizumab [ Time Frame: Predose (0 hr) on Day 1 of Cycle 1 up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) (Detailed timeframe provided in outcome measure description) ]
    Dose-Escalation Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 minutes [min]) on Day 1 of Cycles 1-5, 7 (Cycle length=21 days); Days 2, 4, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 8, 10, 12, 14, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) Expansion Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 min) on Day 1 of Cycles 1-4 (Cycle length=21 days); Days 2, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 2-5, 7, 8, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs)
  • Clearance (CL) of Atezolizumab [ Time Frame: Predose (0 hr) on Day 1 of Cycle 1 up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) (Detailed timeframe provided in outcome measure description) ]
    Dose-Escalation Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 minutes [min]) on Day 1 of Cycles 1-5, 7 (Cycle length=21 days); Days 2, 4, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 8, 10, 12, 14, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) Expansion Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 min) on Day 1 of Cycles 1-4 (Cycle length=21 days); Days 2, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 2-5, 7, 8, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs)
  • Volume at Steady State (Vss) of Atezolizumab [ Time Frame: Predose (0 hr) on Day 1 of Cycle 1 up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) (Detailed timeframe provided in outcome measure description) ]
    Dose-Escalation Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 minutes [min]) on Day 1 of Cycles 1-5, 7 (Cycle length=21 days); Days 2, 4, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 8, 10, 12, 14, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs) Expansion Cohorts: Predose (0 hr), 0.5 hr post-infusion (infusion duration=60 min) on Day 1 of Cycles 1-4 (Cycle length=21 days); Days 2, 8, 15 of Cycle 1; predose (0 hr) on Day 1 of Cycles 2-5, 7, 8, 16, 17, 20, every 8 cycles thereafter (up to approx 7 yrs), at treatment discontinuation & then every 30 days for up to 120 days after last dose of study treatment until death/study closure (up to approx 7 yrs)
  • Percentage of Participants With Best Overall Response, Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [ Time Frame: From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs) ]
  • Percentage of Participants With Best Overall Response, Assessed by Immune-Related Response Criteria (irRC) [ Time Frame: From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs) ]
  • Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]), Assessed by RECIST v1.1 [ Time Frame: From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs) ]
  • Percentage of Participants With Objective Response (CR or PR), Assessed by irRC [ Time Frame: From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs) ]
  • Duration of Objective Response, Assessed by RECIST v1.1 [ Time Frame: Time from the first occurrence of a documented objective response to the time of relapse or death from any cause (up to approx 7 yrs) ]
  • Duration of Objective Response, Assessed by irRC [ Time Frame: Time from the first occurrence of a documented objective response to the time of relapse or death from any cause (up to approx 7 yrs) ]
  • Progression-Free Survival (PFS), Assessed by RECIST v1.1 [ Time Frame: From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs) ]
  • PFS, Assessed by irRC [ Time Frame: From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs) ]
  • Incidence of adverse events graded according to NCI CTCAE v4.0 [ Time Frame: Up to 90 days after the last dose of study treatment or until initiation of another anti cancer therapy, whichever occurs first ]
  • Nature of adverse events graded according to NCI CTCAE v4.0 [ Time Frame: Up to 90 days after the last dose of study treatment or until initiation of another anti cancer therapy, whichever occurs first ]
  • Severity of adverse events graded according to NCI CTCAE v4.0 [ Time Frame: Up to 90 days after the last dose of study treatment or until initiation of another anti cancer therapy, whichever occurs first ]
Not Provided
Not Provided
 
A Study of Atezolizumab (an Engineered Anti-Programmed Death-Ligand 1 [PDL1] Antibody) to Evaluate Safety, Tolerability and Pharmacokinetics in Participants With Locally Advanced or Metastatic Solid Tumors
A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of Atezolizumab (MPDL3280A) Administered Intravenously as a Single Agent to Patients With Locally Advanced or Metastatic Solid Tumors or Hematologic Malignancies
This Phase I, multicenter, first-in-human, open-label, dose-escalation study will evaluate the safety, tolerability, and pharmacokinetics of atezolizumab (MPDL3280A) administered as single agent to participants with locally advanced or metastatic solid malignancies or hematologic malignancies. The study will be conducted in two cohorts: Dose-escalation cohort and Expansion cohort.
Not Provided
Interventional
Phase 1
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Tumors
  • Hematologic Malignancies
Drug: Atezolizumab
Atezolizumab will be administered as IV infusion at eight dose levels (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 20 mg/kg) in dose escalation cohort and at a dose which result in total drug exposure </= exposures achieved at the MTD or MAD, will be selected for expansion cohort.
Other Name: MPDL3280A
  • Experimental: Dose Escalation Cohort: Atezolizumab 0.01 mg/kg
    Participants will receive intravenous (IV) infusion of atezolizumab 0.01 milligrams per kilogram (mg/kg) every 3 weeks (q3w) until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
    Intervention: Drug: Atezolizumab
  • Experimental: Dose Escalation Cohort: Atezolizumab 0.03 mg/kg
    Participants will receive IV infusion of atezolizumab 0.03 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
    Intervention: Drug: Atezolizumab
  • Experimental: Dose Escalation Cohort: Atezolizumab 0.1 mg/kg
    Participants will receive IV infusion of atezolizumab 0.1 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
    Intervention: Drug: Atezolizumab
  • Experimental: Dose Escalation Cohort: Atezolizumab 0.3 mg/kg
    Participants will receive IV infusion of atezolizumab 0.3 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
    Intervention: Drug: Atezolizumab
  • Experimental: Dose Escalation Cohort: Atezolizumab 1 mg/kg
    Participants will receive IV infusion of atezolizumab 1 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
    Intervention: Drug: Atezolizumab
  • Experimental: Dose Escalation Cohort: Atezolizumab 3 mg/kg
    Participants will receive IV infusion of atezolizumab 3 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
    Intervention: Drug: Atezolizumab
  • Experimental: Dose Escalation Cohort: Atezolizumab 10 mg/kg
    Participants will receive IV infusion of atezolizumab 10 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
    Intervention: Drug: Atezolizumab
  • Experimental: Dose Escalation Cohort: Atezolizumab 20 mg/kg
    Participants will receive IV infusion of atezolizumab 20 mg/kg q3w until DLT is reached or up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first.
    Intervention: Drug: Atezolizumab
  • Experimental: Expansion Cohort (Atezolizumab)
    Participants will receive IV infusion of atezolizumab q3w up to end of study or treatment discontinuation or death or until initiation of another anti cancer therapy, whichever occurs first. The dose which result in total drug exposure less than or equal to (</=) exposures achieved at the MTD or maximum administered dose (MAD), will be selected for expansion cohort.
    Intervention: Drug: Atezolizumab

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
661
May 7, 2018
May 7, 2018   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Participants who are 16 to 17 years old would be enrolled after consultation with the Medical Monitor
  • Histologically or cytologically documented, incurable or metastatic solid tumor or hematologic malignancy that is advanced (non-resectable) or recurrent and progressing since the last anti-tumor therapy and for which no recognized standard curative therapy exists
  • Representative tumor specimens in paraffin blocks (preferred) or at least 15 unstained slides, with an associated pathology report
  • Adequate hematologic and end organ function
  • Measurable disease per RECIST v1.1 for participants with solid malignancies. Disease-specific criteria for participants with prostate cancer, glioblastoma multiforme (GBM), malignant lymphoma, or multiple myeloma
  • For women of childbearing potential: agreement to remain abstinent or use contraceptive methods
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • For participants who will undergo serial biopsy in dose-escalation cohort, baseline tumor tissue samples should be of core needle biopsies for deep tumor tissue or organs or excisional or punch biopsies for cutaneous or subcutaneous lesions (>/=5 millimeter [mm] in diameter amenable to serial biopsy)

Exclusion Criteria:

  • Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases
  • Known hypersensitivity to pharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
  • History or risk of autoimmune disease (for example, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis)
  • History of human immunodeficiency virus (HIV) infection, active hepatitis B (chronic or acute), or hepatitis C infection
  • Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1
  • Malignancies other than disease under study within 5 years prior to Cycle 1, Day 1
  • Participants with prior allogeneic bone marrow transplantation or prior solid organ transplantation
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
France,   Spain,   United Kingdom,   United States
 
 
NCT01375842
PCD4989g
2011-001422-23 ( EudraCT Number )
GO27831 ( Other Identifier: Hoffmann-La Roche )
Not Provided
Not Provided
Not Provided
Genentech, Inc.
Genentech, Inc.
Not Provided
Study Director: Clinical Trials Genentech, Inc.
Genentech, Inc.
August 2017

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