Clinical trial NCT01375842: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Tumors
Hematologic Malignancies
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2011-06-17
Enrollment: 661
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Day 1 up to Day 21
measure: Maximum Tolerated Dose (MTD) of Atezolizumab
timeFrame: Day 1 up to Day 21
measure: Recommended Phase 2 Dose (RP2D) of Atezolizumab
timeFrame: Baseline up to time of determination of MTD (up to Day 21)
measure: Percentage of Participants With Adverse Events
timeFrame: 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])
Secondary outcomes:
measure: Percentage of Participants With Anti-Therapeutic Antibodies (ATAs)
timeFrame: 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)
measure: Area Under the Concentration-Time Curve (AUC) of Atezolizumab
timeFrame: 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)
measure: Maximum Serum Concentration (Cmax) of Atezolizumab
timeFrame: 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)
measure: Minimum Serum Concentration (Cmin) of Atezolizumab
timeFrame: 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)
measure: Clearance (CL) of Atezolizumab
timeFrame: 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)
measure: Volume at Steady State (Vss) of Atezolizumab
timeFrame: 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)
measure: Percentage of Participants With Best Overall Response, Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
timeFrame: From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs)
measure: Percentage of Participants With Best Overall Response, Assessed by Immune-Related Response Criteria (irRC)
timeFrame: From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs)
measure: Percentage of Participants With Objective Response (Complete Response [CR] or Partial Response [PR]), Assessed by RECIST v1.1
timeFrame: From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs)
measure: Percentage of Participants With Objective Response (CR or PR), Assessed by irRC
timeFrame: From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs)
measure: Duration of Objective Response, Assessed by RECIST v1.1
timeFrame: 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)
measure: Duration of Objective Response, Assessed by irRC
timeFrame: 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)
measure: Progression-Free Survival (PFS), Assessed by RECIST v1.1
timeFrame: From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs)
measure: PFS, Assessed by irRC
timeFrame: From Baseline up to the first occurrence of progression or death, whichever occurs first (up to approx 7 yrs)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute - Pima Center
state: Arizona
city: Los Angeles
country: United States
facility: The Angeles Clinic
state: California
city: Stanford
country: United States
facility: Stanford Univ Medical Center; Dept Central Pharmacy
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: Uni of Chicago
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Univ Med Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital.
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Med Ctr
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Can Ins
state: Massachusetts
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada - Eastern Avenue
state: Nevada
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: Huntersville
country: United States
facility: Carolina BioOncology Institute; Can Therapy & Res Ctr
state: North Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Inst.
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt
state: Tennessee
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Lyon
country: France
facility: Centre Leon Berard
city: Toulouse
country: France
facility: Institut Claudius Regaud; Departement Oncologie Medicale
city: Villejuif
country: France
facility: Institut Gustave Roussy; Drct
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: London
country: United Kingdom
facility: Barts & London School of Med; Medical Oncology
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
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