A Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Docetaxel in Patients with Non-Small Cell Lung Cancer After Platinum Failure

• Register: EUCTR
• Last refreshed on: 24 September 2018
• Main ID: EUCTR2013-001142-34-BE
• Date of registration: 06/08/2013
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche. Ltd.
• Public title: A Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Docetaxel in Patients with Non-Small Cell Lung Cancer After Platinum Failure
• Scientific title: A PHASE II, OPEN-LABEL, MULTICENTER, RANDOMIZED STUDY TO INVESTIGATE THE EFFICACY AND SAFETY OF ATEZOLIZUMAB (ANTI-PD-L1 ANTIBODY) COMPARED WITH DOCETAXEL IN PATIENTS WITH NON-SMALL CELL LUNG CANCER AFTER PLATINUM FAILURE
• Date of first enrolment: 14/10/2013
• Target sample size: 180
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-001142-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: yes; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, France, Germany, Hungary, Italy, Poland, Spain, Sweden, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TSIL
• Affiliation: F. Hoffmann-La Roche Ltd.

• Name: Trial Information Support Line-TSIL
• Affiliation: F. Hoffmann-La Roche Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
- Aged >= 18 years
- Histologically or cytologically documented locally advanced or metastatic NSCLC; pathological characterization must be sufficient to define patients as having either squamous or non-squamous histology
- Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks (preferred) or at least 15 unstained slides, with an associated pathology report, for central testing and determined to be evaluable for tumor programmed death-ligand 1 (PD-L1) expression prior to study enrollment; patients with fewer than 15 unstained slides available at baseline (but no fewer than 10) may be eligible following discussion with Medical Monitor
- Disease progression during or following treatment with a prior platinum-containing regimen for locally advanced, unresectable/inoperable or metastatic NSCLC or disease recurrence within 6 months of treatment with a platinum-based adjuvant/neoadjuvant regimen
- Measurable disease, as defined by RECIST v1.1
- Eastern Cooperative Oncology Group performance status of 0 or 1
- Life expectancy >= 12 weeks
- Adequate hematologic and end organ function
- For female patients of childbearing potential agreement (by patient) remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of < 1% per year during the treatment period and for 5 months after the last dose of atezolizumab
- Patients must have recovered from all acute toxicities from previous therapy, excluding alopecia
For patients in the docetaxel arm to cross over to receive atezolizumab:
- Patients must have recovered from acute toxicities (Grade <= 1) associated with prior cancer treatment with the exception of higher grade limits associated with specific laboratory result inclusion criteria listed for organ function tests

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 95
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 85

Exclusion criteria:
Cancer-specific exclusions:
- Active or untreated central nervous system metastases as determined by Computerized tomography (CT) or Magnetic resonance imaging evaluation during screening and prior radiographic assessments
- Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >= 2 weeks prior to randomization
- Leptomeningeal disease
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- Uncontrolled tumor-related pain
- Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
- Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome
General medical exclusions:
- Pregnant and lactating women
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- Known hypersensitivity or allergy to Chinese hamster ovary cell-products or any component of the atezolizumab formulation
- History of autoimmune disease
- Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation
- History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan
- Serum albumin < 2.5 g/dL
- Positive test for HIV
- Patients with active hepatitis B or hepatitis C
- Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease
- Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina
- Active tuberculosis
- Severe infections within 4 weeks prior to randomization
- Major surgical procedure within 4 weeks prior to randomization or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis
- Administration of a live, attenuated vaccine within 4 weeks prior to randomization or anticipation that such a live attenuated vaccine will be required during the study
Exclusion criteria related to docetaxel:
- Prior treatment with docetaxel
- History of severe hypersensitivity to docetaxel or to other drugs formulated with polysorbate 80
- Grade >= 2 peripheral neuropathy as defined by National Cancer Institute Common Terminology Criteria
for Adverse Events (NCI CTC AE) v4.0 criteria
- Inability to discontinue use of strong CYP3A4 inhibitors
Exclusion criteria related to atezolizumab:
- Prior treatment with CD137 agonists, anti-CTLA4, anti- programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents
- Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug, whichever is shorter, prior to randomization
- Treatment with systemic immunosuppressive medications within 2 weeks prior to randomization



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

NON-SMALL CELL LUNG CANCER AFTER PLATINUM FAILURE
MedDRA version: 20.0 Level: LLT Classification code 10029514 Term: Non-small cell lung cancer NOS System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Not Applicable
Product Code: MPDL3280A-RO5541267
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not Applicable
Current Sponsor code: MPDL3280A
Other descriptive name: RO5541267
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 125-

Trade Name: Docetaxel
Pharmaceutical Form: Concentrate and solvent for concentrate for solution for infusion
Other descriptive name: DOCETAXEL
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Secondary Objective: •To evaluate the efficacy of atezolizumab compared with docetaxel with respect to anti-tumor effects measured by overall response, duration of response (DOR), and progression free survival (PFS) per Response evaluation criteria in solid tumors (RECIST) v1.1
•To evaluate the efficacy of atezolizumab with respect to anti-tumor effects measured by overall response, DOR, and PFS per modified RECIST
•To characterize the pharmacokinetics of atezolizumab
•To evaluate and compare the patient reported outcomes (PROs) of lung cancer symptoms, patient functioning, and health-related quality of life (HRQoL) between treatment arms as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) and its Lung Cancer Module (LC13)

Main Objective: •To estimate the efficacy of atezolizumab compared with docetaxel as measured by overall survival (OS)
•To evaluate the safety and tolerability of atezolizumab compared with docetaxel
•To evaluate the incidence of anti-therapeutic antibodies (ATAs) against atezolizumab and to explore the potential relationship of the immunogenicity response with pharmacokinetics (PK), safety, and efficacy

Primary end point(s): 1. Overall Survival
2. Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.0
3. Changes in vital signs, physical findings, and clinical laboratory results
4. Incidence of ATA response to atezolizumab and potential correlation with PK, pharmacodynamics, safety, and efficacy parameters

Timepoint(s) of evaluation of this end point: 1. The time from randomization to death from any cause
2. Up to 90 days after last dose of atezolizumab
3. Up to 30 days after last dose of atezolizumab
4. Day 1 of Cycles 1, 2, 3, 4, 8 and 16; at treatment discontinuation visit; and 120 days after last dose of atezolizumab

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: . At partial plus complete response
2. Up to first occurrence of disease progression or death from any cause
3. Time from first occurrence of documented objective response to the time of relapse
4. Day 1 of Cycle 1 (after infusion)
5. Day 1 (prior to infusion) of Cycles 1, 2, 3, 4, 8 and 16; at treatment discontinuation visit; and 120 days after last dose of atezolizumab
6. Up to 30 days after last dose of atezolizumab

Secondary end point(s): 1. Overall response assessed by investigator using RECIST criteria v1.1 and modified RECIST criteria
2. Progression free survival assessed by investigator using RECIST criteria v1.1 and modified RECIST criteria
3. Duration of response assessed by investigator using RECIST criteria v1.1 and modified RECIST criteria
4. Maximum serum atezolizumab concentration
5. Minimum serum atezolizumab concentration
6. HRQoL and lung cancer symptoms as measured by the EORTC QLQ-C30 and QLQ-LC13

Secondary ID(s)

GO28753

Source(s) of Monetary Support

F. Hoffman-La Roche Ltd.