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A Study to Assess Pharmacokinetics and Safety of Atezolizumab Administered Intravenously (IV) as a Single Agent or in Combination With Chemotherapy to Chinese Participants With Locally Advanced or Metastatic Solid Tumors (IMYO29233)

This study is currently recruiting participants.
See Contacts and Locations
Verified August 2017 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02825940
First received: July 5, 2016
Last updated: August 30, 2017
Last verified: August 2017
  Purpose
This Phase I, open-label, multicenter study will evaluate the pharmacokinetics, safety, and preliminary anti-tumor activity of atezolizumab as monotherapy in Chinese participants with locally advanced or metastatic gastric cancer, nasopharyngeal cancer, esophageal cancer, and hepatocellular carcinoma (HCC) that are refractory to standard therapeutic modalities and for whom no further standard therapy is available or who have refused standard therapy; and the safety and preliminary anti-tumor activity of atezolizumab in combination with gemcitabine and cisplatin in Chinese participants with Stage IV, treatment-naive non−small cell lung cancer (NSCLC). The study will consist of a pharmacokinetic (PK) phase and an extension phase.

Condition Intervention Phase
Neoplasms Drug: Atezolizumab Drug: Gemcitabine Drug: Cisplatin Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label Study to Assess the Pharmacokinetics and Safety of Atezolizumab Administered Intravenously as a Single Agent or in Combination With Chemotherapy to Chinese Patients With Locally Advanced or Metastatic Solid Tumors

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • PK Phase: Maximum Observed Plasma Concentration (Cmax) of Atezolizumab [ Time Frame: Pre-dose (0 hours [h]), 0.5h post-dose (PtD) at Day (D) 1; D2,4,8,15 of C1; pre-dose (-2h), 0.5h PtD at D1 of C2,3,4,8,12,16, thereafter every eight cycles until treatment discontinuation or 120 days after last dose (maximum up to 2 years) ]
  • PK Phase: Cmax of Gemcitabine [ Time Frame: Pre-dose (0h), 5-10 minutes before end of dose, 1h PtD on D1 of C1; Pre-dose (-2h), 5-10 minutes before end of dose, 1h PtD on D1 of C3 (maximum up to 2 years) ]
  • PK Phase: Cmax of Cisplatin [ Time Frame: Pre-dose (0h), 5-10 minutes before end of dose, 1h PtD on D1 of C1; Pre-dose (-2h), 5-10 minutes before end of dose, 1h PtD on D1 of C3 (maximum up to 2 years) ]
  • PK Phase: Minimum Observed Plasma Concentration (Cmin) of Atezolizumab [ Time Frame: Pre-dose (0h), 0.5h PtD at D1; D2,4,8,15 of C1; pre-dose (-2h), 0.5h PtD at D1 of C2,3,4,8,12,16, thereafter every eight cycles until treatment discontinuation or 120 days after last dose (maximum up to 2 years) ]
  • PK Phase: Cmin of Gemcitabine [ Time Frame: Pre-dose (0h), 5-10 minutes before end of dose, 1h PtD on D1 of C1; Pre-dose (-2h), 5-10 minutes before end of dose, 1h PtD on D1 of C3 (maximum up to 2 years) ]
  • PK Phase: Cmin of Cisplatin [ Time Frame: Pre-dose (0h), 5-10 minutes before end of dose, 1h PtD on D1 of C1; Pre-dose (-2h), 5-10 minutes before end of dose, 1h PtD on D1 of C3 (maximum up to 2 years) ]
  • PK Phase: Accumulation Ratio (Rac) of Atezolizumab Based on Concentrations After the First Dose and at Steady State [ Time Frame: Pre-dose (0h), 0.5h PtD at D 1; D2, 4, 8, 15 of C1; pre-dose (-2h), 0.5h PtD at D1 of C2,3,4,8,12,16, thereafter every eight cycles until treatment discontinuation or 120 days after last dose (maximum up to 2 years) ]
  • PK Phase: Rac of Gemcitabine Based on Concentrations After the First Dose and at Steady State [ Time Frame: Pre-dose (0h), 5-10 minutes before end of dose, 1h PtD on D1 of C1; Pre-dose (-2h), 5-10 minutes before end of dose, 1h PtD on D1 of C3 (maximum up to 2 years) ]
  • PK Phase: Rac of Cisplatin Based on Concentrations After the First Dose and at Steady State [ Time Frame: Pre-dose (0h), 5-10 minutes before end of dose, 1h PtD on D1 of C1; Pre-dose (-2h), 5-10 minutes before end of dose, 1h PtD on D1 of C3 (maximum up to 2 years) ]
  • PK Phase: Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of Atezolizumab [ Time Frame: Pre-dose (0h), 0.5h PtD at D 1; D2,4,8,15 of C1; pre-dose (-2h), 0.5h PtD at D1 of C2,3,4,8,12,16, thereafter every eight cycles until treatment discontinuation or 120 days after last dose (maximum up to 2 years) ]
  • PK Phase: AUC (0-inf) of Gemcitabine [ Time Frame: Pre-dose (0h), 5-10 minutes before end of dose, 1h PtD on D1 of C1; Pre-dose (-2h), 5-10 minutes before end of dose, 1h PtD on D1 of C3 (maximum up to 2 years) ]
  • PK Phase: AUC (0-inf) of Cisplatin [ Time Frame: Pre-dose (0h), 5-10 minutes before end of dose, 1h PtD on D1 of C1; Pre-dose (-2h), 5-10 minutes before end of dose, 1h PtD on D1 of C3 (maximum up to 2 years) ]
  • PK Phase: Systemic Clearance (CL) of Atezolizumab [ Time Frame: Pre-dose (0h), 0.5h PtD at D1; D2,4,8,15 of C1; pre-dose (-2h), 0.5h PtD at D1 of C2,3,4,8,12,16, thereafter every eight cycles until treatment discontinuation or 120 days after last dose (maximum up to 2 years) ]
  • PK Phase: CL of Gemcitabine [ Time Frame: Pre-dose (0h), 5-10 minutes before end of dose, 1h PtD on D1 of C1; Pre-dose (-2h), 5-10 minutes before end of dose, 1h PtD on D1 of C3 (maximum up to 2 years) ]
  • PK Phase: CL of Cisplatin [ Time Frame: Pre-dose (0h), 5-10 minutes before end of dose, 1h PtD on D1 of C1; Pre-dose (-2h), 5-10 minutes before end of dose, 1h PtD on D1 of C3 (maximum up to 2 years) ]
  • PK Phase: Volume of Distribution at Steady State (Vss) of Atezolizumab [ Time Frame: Pre-dose (0h), 0.5h PtD at D1; D2,4,8,15 of C1; pre-dose (-2h), 0.5h PtD at D1 of C2,3,4,8,12,16, thereafter every eight cycles until treatment discontinuation or 120 days after last dose (maximum up to 2 years) ]
  • PK Phase: Vss of Gemcitabine [ Time Frame: Pre-dose (0h), 5-10 minutes before end of dose, 1h PtD on D1 of C1; Pre-dose (-2h), 5-10 minutes before end of dose, 1h PtD on D1 of C3 (maximum up to 2 years) ]
  • PK Phase: Vss of Cisplatin [ Time Frame: Pre-dose (0h), 5-10 minutes before end of dose, 1h PtD on D1 of C1; Pre-dose (-2h), 5-10 minutes before end of dose, 1h PtD on D1 of C3 (maximum up to 2 years) ]
  • PK Phase: Plasma Half-Life (t1/2) of Atezolizumab [ Time Frame: Pre-dose (0h), 0.5h PtD at D1; D2,4,8,15 of C1; pre-dose (-2h), 0.5h PtD at D1 of C2,3,4,8,12,16, thereafter every eight cycles until treatment discontinuation or 120 days after last dose (maximum up to 2 years) ]
  • PK Phase: t1/2 of Gemcitabine [ Time Frame: Pre-dose (0h), 5-10 minutes before end of dose, 1h PtD on D1 of C1; Pre-dose (-2h), 5-10 minutes before end of dose, 1h PtD on D1 of C3 (maximum up to 2 years) ]
  • PK Phase: t1/2 of Cisplatin [ Time Frame: Pre-dose (0h), 5-10 minutes before end of dose, 1h PtD on D1 of C1; Pre-dose (-2h), 5-10 minutes before end of dose, 1h PtD on D1 of C3 (maximum up to 2 years) ]
  • Extension Phase: Cmax of Atezolizumab [ Time Frame: Pre-dose (0h), 0.5h PtD at D1; D2,4,8,15 of C1; pre-dose (-2h), 0.5h PtD at D1 of C2,3,4,8,12,16, thereafter every eight cycles until treatment discontinuation or 120 days after last dose (maximum up to 2 years) ]
  • Extension Phase: Cmax of Gemcitabine [ Time Frame: Pre-dose (0h), 5-10 minutes before end of dose, 1h PtD on D1 of C1; Pre-dose (-2h), 5-10 minutes before end of dose, 1h PtD on D1 of C3 (maximum up to 2 years) ]
  • Extension Phase: Cmax of Cisplatin [ Time Frame: Pre-dose (0h), 5-10 minutes before end of dose, 1h PtD on D1 of C1; Pre-dose (-2h), 5-10 minutes before end of dose, 1h PtD on D1 of C3 (maximum up to 2 years) ]
  • Extension Phase: Cmin of Atezolizumab [ Time Frame: Pre-dose (0h), 0.5h PtD at D1; D2,4,8,15 of C1; pre-dose (-2h), 0.5h PtD at D1 of C2,3,4,8,12,16, thereafter every eight cycles until treatment discontinuation or 120 days after last dose (maximum up to 2 years) ]
  • Extension Phase: Cmin of Gemcitabine [ Time Frame: Pre-dose (0h), 5-10 minutes before end of dose, 1h PtD on D1 of C1; Pre-dose (-2h), 5-10 minutes before end of dose, 1h PtD on D1 of C3 (maximum up to 2 years) ]
  • Extension Phase: Cmin of Cisplatin [ Time Frame: Pre-dose (0h), 5-10 minutes before end of dose, 1h PtD on D1 of C1; Pre-dose (-2h), 5-10 minutes before end of dose, 1h PtD on D1 of C3 (maximum up to 2 years) ]
  • Extension Phase: Rac of Atezolizumab Based on Concentrations After the First Dose and at Steady State [ Time Frame: Pre-dose (0h), 0.5h PtD at D1; D2,4,8,15 of C1; pre-dose (-2h), 0.5h PtD at D1 of C2,3,4,8,12,16, thereafter every eight cycles until treatment discontinuation or 120 days after last dose (maximum up to 2 years) ]
  • Extension Phase: Rac of Gemcitabine Based on Concentrations After the First Dose and at Steady State [ Time Frame: Pre-dose (0h), 5-10 minutes before end of dose, 1h PtD on D1 of C1; Pre-dose (-2h), 5-10 minutes before end of dose, 1h PtD on D1 of C3 (maximum up to 2 years) ]
  • Extension Phase: Rac of Cisplatin Based on Concentrations After the First Dose and at Steady State [ Time Frame: Pre-dose (0h), 5-10 minutes before end of dose, 1h PtD on D1 of C1; Pre-dose (-2h), 5-10 minutes before end of dose, 1h PtD on D1 of C3 (maximum up to 2 years) ]
  • PK Phase: Number of Participants With Anti-therapeutic Antibody (ATA) Response [ Time Frame: Baseline up to treatment discontinuation (maximum up to 2 years) ]
  • Extension Phase: Number of Participants With Anti-Therapeutic Antibody Response [ Time Frame: Baseline up to treatment discontinuation (maximum up to 2 years) ]
  • Extension Phase: Number 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 (maximum up to 2 years) ]

Secondary Outcome Measures:
  • Extension Phase: Percentage of Participants With Best Overall Response Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or modified Response Evaluation Criteria in Solid Tumors (mRECIST) [ Time Frame: From Baseline, thereafter every 6 weeks until disease progression, death, or loss to follow-up (maximum up to 2 years) ]
  • Extension Phase: Percentage of Participants With Objective Response, Defined as a Confirmed Complete or Partial Response Based on RECIST v1.1 or mRECIST [ Time Frame: From Baseline, thereafter every 6 weeks until disease progression, death, or loss to follow-up (maximum up to 2 years) ]
  • Extension Phase: Duration of Response Based on RECIST v1.1 or mRECIST [ Time Frame: From Baseline, thereafter every 6 weeks until disease progression, death, or loss to follow-up (maximum up to 2 years) ]
  • Extension Phase: Percentage of Participants With Disease Progression Based on RECIST v1.1 or mRECIST [ Time Frame: From Baseline, thereafter every 6 weeks until disease progression, death, or loss to follow-up (maximum up to 2 years) ]
  • Extension Phase: Time to Disease Progression Based on RECIST v1.1 or mRECIST [ Time Frame: From Baseline, thereafter every 6 weeks until disease progression, death, or loss to follow-up (maximum up to 2 years) ]
  • Extension Phase: Percentage of Participants With Progression-free Survival (PFS) Based on RECIST v1.1 or mRECIST [ Time Frame: From Baseline, thereafter every 6 weeks until disease progression, death, or loss to follow-up (maximum up to 2 years) ]
  • Extension Phase: PFS Based on RECIST v1.1 or mRECIST [ Time Frame: From Baseline, thereafter every 6 weeks until disease progression, death, or loss to follow-up (maximum up to 2 years) ]
  • Extension Phase: Percentage of Participants who Died [ Time Frame: From Baseline, thereafter every 6 weeks until disease progression, death, or loss to follow-up (maximum up to 2 years) ]
  • Extension Phase: Overall survival [ Time Frame: From Baseline, thereafter every 6 weeks until disease progression, death, or loss to follow-up (maximum up to 2 years) ]
  • Extension Phase: Percentage of Participants Who Were Alive at 6 Months and 1 Year [ Time Frame: 6 Months and 1 Year ]

Estimated Enrollment: 120
Actual Study Start Date: August 4, 2016
Estimated Study Completion Date: July 10, 2020
Estimated Primary Completion Date: May 28, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atezolizumab Monotherapy: PK and Extension Phases
Participants during the PK and extension phases of the study will receive atezolizumab alone at a dose of 1200 milligrams (mg) IV every 3 weeks (q3w) (in 21-day cycles) continuously until loss of clinical benefit, disease progression, unacceptable toxicity, participant or physician decision to discontinue, or death. Study treatment may continue beyond disease progression based on the investigator's discretion.
Drug: Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg IV q3w (in 21-day cycles), except for participants with NSCLC who will be administered atezolizumab at a dose of 1200 mg IV on Day 1.
Other Names:
  • MPDL3280A
  • RO5541267
Experimental: Atezolizumab and Chemotherapy: Extension Phase
Participants during the extension phase of the study will receive atezolizumab at a dose of 1200 mg IV on Day 1 in combination with gemcitabine at a dose of 1250 milligrams per square meter (mg/m^2) on Days 1 and 8 and cisplatin at a dose of 75 mg/m^2 on Day 1 (four or six 21-day cycles at the discretion of the investigator), followed by atezolizumab as a single agent at a dose of 1200 mg IV q3w on Day 1 of a 21-day cycle) as maintenance treatment continuously until loss of clinical benefit, disease progression, unacceptable toxicity, participant or physician decision to discontinue, or death. Study treatment may continue beyond disease progression based on the investigator's discretion.
Drug: Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg IV q3w (in 21-day cycles), except for participants with NSCLC who will be administered atezolizumab at a dose of 1200 mg IV on Day 1.
Other Names:
  • MPDL3280A
  • RO5541267
Drug: Gemcitabine
Gemcitabine will be administered to participants with NSCLC at a dose of 1250 mg/m^2 on Days 1 and 8.
Drug: Cisplatin
Cisplatin will be administered to participants with NSCLC at a dose of 75 mg/m^2 on Day 1.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically documented, incurable or metastatic solid tumor that is advanced (non-resectable) or recurrent and progressing since the last the anti-tumor therapy and for which no recognized standard curative therapy exists or who have refused the standard therapy
  • Adequate hematologic and end organ function
  • Measurable disease per RECIST v1.1 or mRECIST
  • Eastern Cooperative Oncology Group Performance Status of 0 or 1
  • Women who are not postmenopausal (greater than or equal to (>=) 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment
  • Women of childbearing potential must agree to remain abstinent or use contraceptive methods specified in the study
  • For enrollment into the China extension cohort, residence in the People's Republic of China
  • A representative formalin-fixed paraffin-embedded (FFPE) tumor specimen in paraffin block (preferred) or 15 or more unstained, freshly cut, serial sections (on slides) from an FFPE tumor specimen is required for participation in this study. This specimen must be accompanied by the pathology report
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of less than (<) 1% per year during the treatment period and for at least 90 days 5 months after the last dose of atezolizumab, or 6 months after the last dose of cisplatin or gemcitabine, whichever is longer, if combined
  • For men in the NSCLC cohort only: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm
  • For participants in the NSCLC Cohort: Histologically or cytologically confirmed Stage IV NSCLC (per the Union Internationale contre le Cancer/American Joint Committee on Cancer staging system)
  • For participants in the NSCLC Cohort: No prior treatment for Stage IV NSCLC
  • For participants in the NSCLC Cohort: Participants who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last chemotherapy, radiotherapy, or chemoradiotherapy cycle

Exclusion Criteria:

  • Any approved anti-cancer therapy, including chemotherapy, targeted therapy or hormonal therapy less than (<) 5 half-lives prior to initiation of study treatment
  • Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment
  • Uncontrolled hypercalcemia (greater than (>) 1.5 millimoles per liter (mmol/L) ionized calcium or calcium >12 milligram per deciliter (mg/dL) or corrected serum calcium greater than the upper limit of normal) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, fatty liver, and inherited liver disease
  • Participants with acute leukemia, accelerated/blast-phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma
  • Active or untreated central nervous system metastases as determined by computed tomography or magnetic resonance imaging evaluation during screening and prior radiographic assessments
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the participant at high risk from treatment complications
  • History of human immunodeficiency virus, hepatitis B (except the HCC cohort), or hepatitis C infection
  • For participants in the NSCLC Cohort: Known tumor programmed death-ligand 1 (PD-L1) expression status as determined by an immunohistochemistry assay during participation in other clinical studies (e.g., participants whose PD-L1 expression status was determined during screening for entry into a study with anti−programmed death 1 or anti−PD-L1 antibodies but were not eligible are excluded)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02825940

Contacts
Contact: Reference Study ID Number: YO29233 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
China
Beijing Cancer Hospital Recruiting
Beijing, China, 100142
Cancer Center, Sun Yat-sen University of Medical Sciences; Department of Medical Oncology Recruiting
Guangzhou, China, 510060
Sir Run Run Shaw Hospital Recruiting
Hangzhou, China, 310016
Harbin Medical University Cancer Hospital Recruiting
Harbin, China, 150081
Harbin Medical University Cancer Hospital Not yet recruiting
Harbin, China, 150081
Fudan University Shanghai Cancer Center Recruiting
Shanghai, China, 200032
Zhongshan Hospital Fudan University Recruiting
Shanghai, China, 200032
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02825940     History of Changes
Other Study ID Numbers: YO29233
Study First Received: July 5, 2016
Last Updated: August 30, 2017

Additional relevant MeSH terms:
Gemcitabine
Cisplatin
Antibodies, Monoclonal
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 21, 2017