A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Preliminary Efficacy of Atezolizumab (Anti-Programmed Death-Ligand 1 [PD-L1] Antibody) in Pediatric and Young Adult Participants With Solid Tumors

February 24, 2020 updated by: Hoffmann-La Roche

An Early-Phase, Multicenter, Open-Label Study of the Safety and Pharmacokinetics of Atezolizumab (MPDL3280A) In Pediatric and Young Adult Patients With Previously Treated Solid Tumors

This early phase, multicenter, open-label, single-arm study evaluated the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary efficacy of atezolizumab in pediatric and young adult participants with solid tumors for which prior treatment was proven to be ineffective.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

87

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Alberta
      • Calgary, Alberta, Canada, T3B 6A8
        • Alberta Children's Hospital
      • København Ø, Denmark, 2100
        • Rigshospitalet; BØRNEUNGEKLINIKKEN, Ambulatoriet for kræft- og Blodsygdomme hos børn og unge
      • Lyon, France, 69373
        • Centre Léon Bérard, Institut d'Hémato-Oncologie Pédiatrique
      • Paris, France, 75231
        • Institut Curie, Oncologie Pédiatrique
      • Villejuif, France, 94805
        • Institut Gustave Roussy; Service Pediatrique
      • Frankfurt, Germany, 60590
        • Klinik Johann Wolfgang von Goethe Uni
      • Petach-Tikva, Israel, 49100
        • Schneider Children's Medical Center
    • Lazio
      • Roma, Lazio, Italy, 00165
        • Ospedale Pediatrico Bambino Gesù - IRCCS; Dipartimento di Onco-Ematologia Pediatrica
    • Liguria
      • Genova, Liguria, Italy, 16147
        • IRCCS Istituto Giannina Gaslini; Unità Operativa Oncologica Pediatrica
    • Lombardia
      • Milano, Lombardia, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale dei Tumori; Struttura Complessa di Pediatria Oncologica
    • Piemonte
      • Torino, Piemonte, Italy, 10126
        • Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino
    • Veneto
      • Padova, Veneto, Italy, 35128
        • Azienda Ospedaliera di Padova; Clinica di Onco-ematologia pediatrica
      • Rotterdam, Netherlands, 3015 GJ
        • Erasmus MC / location Sophia Kinderziekenhuis
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebrón
      • Madrid, Spain, 28009
        • Hospital Infantil Universitario Niño Jesús
      • Valencia, Spain, 46026
        • Hospital Universitari i Politecnic La Fe de Valencia
    • Barcelona
      • Esplugues De Llobregas, Barcelona, Spain, 08950
        • Hospital Sant Joan de Deu
      • Zürich, Switzerland, 8032
        • Universitäts-Kinderspital; Abteilung für Onkologie
      • Birmingham, United Kingdom, B4 6NH
        • Birmingham Children's Hospital
      • Bristol, United Kingdom, BS2 8BJ
        • Bristol Royal Hospital for Children
      • Leeds, United Kingdom, LS1 3EX
        • Leeds General Infirmary; Paediatric Oncology & Haematology
      • Newcastle Upon Tyne, United Kingdom, NE1 4LP
        • The Royal Victoria Infirmary; Paediatric and Adolescent Oncology Unit
      • Surrey, United Kingdom, SM2 5PT
        • Royal Marsden Hospital; Pediatric Unit
    • Arkansas
      • Little Rock, Arkansas, United States, 72202
        • Arkansas Children's Hospital
    • California
      • Palo Alto, California, United States, 94304
        • Stanford University/Lucile Packard Children's Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Penn State Milton S. Hershey Medical Center
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center at San Antonio

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 30 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Pediatric solid tumor (including Hodgkin's and Non-Hodgkin's lymphoma), for which prior treatment had proven to be ineffective (that is, relapsed or refractory) or intolerable
  • Disease that is measurable as defined by RECIST v1.1, mINRC, Revised Response Criteria for Malignant Lymphoma, RANO criteria (as appropriate) or evaluable by nuclear medicine techniques, immunocytochemistry techniques, tumor markers, or other reliable measures
  • Archival tumor tissue block or 15 freshly cut, unstained, serial slides available for submission, or willingness to undergo a core or excisional biopsy prior to enrollment (fine-needle aspiration, brush biopsy, and lavage samples are not acceptable).

Participants with fewer than 15 slides available may be eligible for study entry following discussion with Medical Monitor

  • Lansky Performance Status (participants less than [<] 16 years old) or Karnofsky Performance Status (participants greater than or equal to [>=] 16 years old) >=50
  • Life expectancy >=3 months, in the investigator's judgment
  • Adequate hematologic and end organ function, confirmed by laboratory results obtained within 28 days prior to initiation of study drug

Exclusion Criteria:

  • Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases, except ATRT
  • Treatment with high-dose chemotherapy and hematopoietic stem-cell rescue within 3 months prior to initiation of study drug
  • Prior allogeneic hematopoietic stem-cell transplantation or prior solid-organ transplantation
  • Treatment with chemotherapy (other than high-dose chemotherapy as described above) or differentiation therapy (such as retinoic acid) or immunotherapy (such as anti-GD2 antibody treatment) within 3 weeks prior to initiation of study drug or, if treatment included nitrosoureas, within 6 weeks prior to initiation of study drug
  • Treatment with thoracic or mediastinal radiotherapy within 3 weeks prior to initiation of study drug
  • Treatment with hormonal therapy (except hormone replacement therapy or oral contraceptives) or biologic therapy within 4 weeks or 5 half-lives, whichever is shorter, prior to initiation of study drug. This requirement may be waived at the investigator's request if the participant has recovered from therapeutic toxicity to the degree specified in the protocol, with approval of the Medical Monitor
  • Treatment with a long-acting hematopoietic growth factor within 2 weeks prior to initiation of study drug or a short-acting hematopoietic growth factor within 1 week prior to initiation of study drug
  • Treatment with investigational therapy (with the exception of cancer therapies as described above) within 4 weeks prior to initiation of study drug
  • Treatment with a live vaccine or a live, attenuated vaccine (e.g., nasal spray of live attenuated influenza vaccine or FluMist®) within 4 weeks prior to initiation of study drug or anticipation that such treatment will be required during the study or within 5 months after the final dose of study drug
  • Treatment with herbal cancer therapy within 1 week prior to initiation of study drug
  • Prior treatment with cluster of differentiation 137 (CD137) agonists or immune checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4), anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibodies
  • Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin 2 [IL-2]) within 6 weeks or five drug elimination half-lives prior to Day 1 of Cycle 1, whichever is longer
  • Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents) at the time of initiation of study drug, or anticipated requirement for systemic immunosuppressive medications during the study
  • Current treatment with therapeutic anticoagulants
  • Any non-hematologic toxicity (excluding alopecia) from prior treatment that has not resolved to Grade less than or equal to (<=) 1 (per National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.0) at screening
  • Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Atezolizumab
Participants received intravenous (IV) infusion of atezolizumab (maximum 1200 milligrams [mg]) on Day 1 of each 21-day cycle.
Atezolizumab was administered as IV infusion (maximum 1200 mg) on Day 1 of each 21-day cycle.
Other Names:
  • RO5541267; MPDL3280A; Tecentriq

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With an Objective Response (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Participants With Solid Tumors
Time Frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Note: In Cohort 5, the response was observed in a rhabdoid tumor. Participant was erroneously enrolled in the Non-rhabdomyosarcoma soft tissue sarcoma cohort.
Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Modified International Neuroblastoma Response Criteria (mINRC) in Participants With Neuroblastoma
Time Frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma
Time Frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Response Assessment in Neuro-Oncology (RANO) Criteria in Participants With Atypical Teratoid Rhabdoid Tumor (ATRT)
Time Frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Percentage of Participants With Clinical Benefit as Determined by the Investigator According to RECIST v1.1 Criteria in Participants With Osteosarcoma
Time Frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Progression-Free Survival (PFS) as Determined by the Investigator Using RECIST v1.1 in Participants With Solid Tumors
Time Frame: Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)
Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)
PFS as Determined by the Investigator Using mINRC in Participants With Neuroblastoma
Time Frame: Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)
Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)
PFS as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma
Time Frame: Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)
Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)
PFS as Determined by the Investigator Using RANO Criteria in Participants With ATRT
Time Frame: Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)
Baseline until first documented occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 42 months)
Percentage of Participants Adverse Events, Serious Adverse Events and Adverse Events of Special Interest
Time Frame: From baseline up to approximately 42 months
From baseline up to approximately 42 months
Maximum Serum Concentration (Cmax) of Atezolizumab
Time Frame: Predose (PRD; 0 hours [hr]), 0.5 hr post-infusion (P-I; infusion duration=30-60 minutes) on Day (D) 1 of Cycle (Cy) 1 and 4 (1 Cy=21 days)
Predose (PRD; 0 hours [hr]), 0.5 hr post-infusion (P-I; infusion duration=30-60 minutes) on Day (D) 1 of Cycle (Cy) 1 and 4 (1 Cy=21 days)
Minimum Serum Concentration (Cmin) of Atezolizumab
Time Frame: PRD (0 hr) on D1 of Cy2,3,4,8, 12, 16 (1 Cy=21 days) and every 8 cycles thereafter; at any time during visit at study drug discontinuation visit, at least 90 days (maximum 150 days) after the last dose of study drug (up to approximately 42 months)
PRD (0 hr) on D1 of Cy2,3,4,8, 12, 16 (1 Cy=21 days) and every 8 cycles thereafter; at any time during visit at study drug discontinuation visit, at least 90 days (maximum 150 days) after the last dose of study drug (up to approximately 42 months)
Atezolizumab Serum Concentration at Washout
Time Frame: At least 90 days (maximum 150 days) after last dose of study drug (up to approximately 42 months)
At least 90 days (maximum 150 days) after last dose of study drug (up to approximately 42 months)
Area Under the Concentration-Time Curve (AUC) of Atezolizumab
Time Frame: PRD (0 hr), 0.5 hr P-I (infusion duration=30-60 minutes) on D1 of Cy1; at any time during visit on Cy1D8 (1 Cy=21 days)
PRD (0 hr), 0.5 hr P-I (infusion duration=30-60 minutes) on D1 of Cy1; at any time during visit on Cy1D8 (1 Cy=21 days)
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
Time Frame: PRD (0 hr) on D1 of Cy1,2,3,4,8,12,16 (1 Cy=21 days) & every 8 cycles thereafter; at any time during visit on Cy1D8, study drug discontinuation, at least 90 days (maximum 150 days) after last dose of study drug (up to approximately 42 months)
PRD (0 hr) on D1 of Cy1,2,3,4,8,12,16 (1 Cy=21 days) & every 8 cycles thereafter; at any time during visit on Cy1D8, study drug discontinuation, at least 90 days (maximum 150 days) after last dose of study drug (up to approximately 42 months)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 Criteria in Participants With Solid Tumors
Time Frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
DOR as Determined by the Investigator Using mINRC in Participants With Neuroblastoma
Time Frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
DOR as Determined by the Investigator Using Revised Response Criteria for Malignant Lymphoma for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma
Time Frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
DOR as Determined by the Investigator Using RANO Criteria in Participants With ATRT
Time Frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Overall Survival (OS)
Time Frame: Baseline until death (up to approximately 42 months)
Baseline until death (up to approximately 42 months)
Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors
Time Frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using Immune-Related Response Criteria (irRC) for Participants With Neuroblastoma
Time Frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Percentage of Participants With an Objective Response (CR or PR) as Determined by the Investigator Using irRC for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma
Time Frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
PFS as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors
Time Frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
PFS as Determined by the Investigator Using irRC for Participants With Neuroblastoma
Time Frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
PFS as Determined by the Investigator Using irRC for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma
Time Frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
DOR as Determined by the Investigator Using Immune-Modified RECIST v1.1 for Participants With Other Solid Tumors
Time Frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
DOR as Determined by the Investigator Using irRC for Participants With Neuroblastoma
Time Frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
DOR as Determined by the Investigator Using irRC for Participants With Hodgkin's Lymphoma or Non-Hodgkin's Lymphoma
Time Frame: Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Baseline until disease progression, or death from any cause, whichever occurs first (up to approximately 42 months)
Optimal Dose of Atezolizumab in Pediatric Adult Participants
Time Frame: From baseline up to approximately 42 months
Atezolizumab was administered on Day 1 only for a cycle duration of 3 weeks.
From baseline up to approximately 42 months
Optimal Dose of Atezolizumab in Young Adult Participants
Time Frame: From baseline up to approximately 42 months
Atezolizumab was administered on Day 1 only for a cycle duration of 3 weeks.
From baseline up to approximately 42 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 30, 2015

Primary Completion (Actual)

June 6, 2019

Study Completion (Actual)

June 6, 2019

Study Registration Dates

First Submitted

August 18, 2015

First Submitted That Met QC Criteria

September 3, 2015

First Posted (Estimate)

September 4, 2015

Study Record Updates

Last Update Posted (Actual)

February 25, 2020

Last Update Submitted That Met QC Criteria

February 24, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GO29664
  • 2014-004697-41 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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