| CTRI Number |
CTRI/2017/11/010690 [Registered on: 29/11/2017] Trial Registered Prospectively |
| Last Modified On: |
11/09/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
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Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
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Public Title of Study
|
A clinical trial to study the efficacy and safety of Atezolizumab compared with standard Chemotherapy in Non-Small Cell Lung Cancer patients with poor performance status. |
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Scientific Title of Study
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A Phase III, open-label, multicenter, randomized study to investigate the efficacy and safety of Atezolizumab compared with Chemotherapy in patients with treatment-naïve advanced or recurrent (Stage IIIb not amenable for multimodality treatment) or Metastatic (Stage IV) Non-small Cell Lung Cancer who are deemed unsuitable for platinum-containing Therapy |
| Trial Acronym |
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Secondary IDs if Any
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| Secondary ID |
Identifier |
| Version 1.0 dated 13 Feb 2017 |
Protocol Number |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Raju Titus Chacko |
| Designation |
Head & Professor - Medical Oncology |
| Affiliation |
|
| Address |
Department of Medical Oncology, Christian Medical College, Ida Scudder Road
Vellore
TAMIL NADU
632004
India |
| Phone |
914162283040 |
| Fax |
914163073410 |
| Email |
rchacko@cmcvellore.ac.in |
|
Details of Contact Person
Scientific Query
Modification(s)
|
| Name |
Dr Viraj Suvarna |
| Designation |
Chief Medical Officer |
| Affiliation |
Roche Products (India) Pvt. Ltd. |
| Address |
146-B, 166 A, Unit No. 7, 8, 9
8th Floor, R City Office, R City Mall, Lal Bahadur Shastri Marg, Ghatkopar, Mumbai - 400 086,
Maharashtra, India
Mumbai
MAHARASHTRA
400086
India |
| Phone |
9820006317 |
| Fax |
|
| Email |
viraj.suvarna@roche.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Amol Pawar |
| Designation |
Manager -Clinical Operations |
| Affiliation |
Roche Products (India) Pvt. Ltd. |
| Address |
146-B, 166 A, Unit No. 7, 8, 9
8th Floor, R City Office, R City Mall, Lal Bahadur Shastri Marg, Ghatkopar
Mumbai
MAHARASHTRA
400086
India |
| Phone |
8080780992 |
| Fax |
|
| Email |
amol.pawar@roche.com |
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Source of Monetary or Material Support
Modification(s)
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| F. Hoffmann-La Roche Ltd.
CH-4070, Basel, Switzerland
|
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Primary Sponsor
|
| Name |
F HoffmannLa Roche Ltd |
| Address |
CH-4070, Basel, Switzerland
|
| Type of Sponsor |
Pharmaceutical industry-Global |
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Details of Secondary Sponsor
Modification(s)
|
| Name |
Address |
| Roche Products India Pvt Ltd |
146-B, 166 A, Unit No. 7, 8, 9, 8th Floor, R City Office, R City Mall,
Lal Bahadur Shastri Marg,
Ghatkopar, Mumbai - 400 086, Maharashtra, India
India
|
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Countries of Recruitment
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Luxembourg
Peru
Poland
Portugal
Slovakia
Spain
Switzerland
United Kingdom
Viet Nam
Algeria
Belgium
Brazil
Bulgaria
Canada
China
Colombia
Czech Republic
Denmark
Germany
India
Ireland
Italy
Kazakhstan
Mexico
Romania |
Sites of Study
Modification(s)
|
| No of Sites = 7 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Ashish Kaushal |
HCG Cancer Center |
Sola Science City Road,Near Sola Bridge,S.G.Highway, Ahmedabad-380060, Gujarat
Ahmadabad
GUJARAT |
9978297842
drashish4@yahoo.co.in |
| Dr Rajnish Nagarkar |
HCG Manavata Cancer Center |
Behind Shivang Auto, Mumbai Naka,Nashik-422002,Maharashtra,India
Nashik
MAHARASHTRA |
9823061929
02536661111
drraj@manavatacancercentre.com |
| Dr Manish Kumar Singhal |
Indraprastha Apollo Hospitals |
Sarita Vihar, Delhi-Mathura Road, New Delhi 110076, India
New Delhi
DELHI |
9818736533
singhaloncocare@yahoo.co.in |
| Dr Rajesh Mistry |
Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute |
Department of Medical Oncology, Rao Saheb Achutrao, Patwardhan Marg, Four Bunglows, Andheri West, Mumbai, Maharashtra 400053, India
Mumbai
MAHARASHTRA |
919320361267
912230970177
mistryrc@gmail.com |
| Dr DC Doval |
Rajiv Gandhi Cancer Institute and Research Center |
Department of Medical Oncology, Sector 5, Rohini, New Delhi 110085
North West
DELHI |
911147022428
911127051037
dcdoval@gmail.com |
| Dr Moses Arunsingh S |
Tata Medical Center |
14 Major Arterial Road (EW), Newtown, Rajarhat,
Kolkata - 700160, West Bengal, India
Kolkata
WEST BENGAL |
9007395797
moses.arunsingh@tmckolkata.com |
| Dr Prabhash Kumar |
Tata Memorial Centre |
Department of Medical Oncology, Dr. E.Borges Road, Parel, Mumbai-400012, India.
Mumbai
MAHARASHTRA |
912224177214
912224171734
kprabhash1@gmail.com |
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Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 7 |
| Name of Committee |
Approval Status |
| Institutional Review Board, Tata Medical Center, Kolkata |
Approved |
| HCG Multi Speciality Ethics Committee |
Approved |
| Institutional Ethics Commi |
Approved |
| Institutional Ethics Committee, Tata Memorial Centre |
Approved |
| Institutional Review Board, Rajiv Gandhi Cancer Institute & Research Center |
Approved |
| Institutional Scientific and Ethics Board |
Approved |
| Manavata Clinical Research Institute Ethics Committee |
Approved |
|
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Regulatory Clearance Status from DCGI
|
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Health Condition / Problems Studied
Modification(s)
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Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Atezolizumab |
The dose of atezolizumab in this study will be 1200 mg administered by intravenous infusion on Day 1 of each 21-day cycle. |
| Comparator Agent |
Vinorelbine [oral or intravenous] or Gemcitabine |
Both these drugs will be administered as per the product label |
|
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Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
1. Signed Informed Consent Form
2. Women or men aged ≥18 years
3. Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC
4. No sensitizing epidermal growth factor receptor (EGFR) mutation (L858R or exon 19 deletions) or anaplastic lymphoma kinase (ALK) fusion oncogene detected
5. No prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC
6.Life expectancy ≥ 8 weeks
7.Deemed unsuitable for platinum-containing chemotherapy by the investigator due to poor performance status (ECOG PS of 2-3)
8. Measurable disease, as defined by RECIST v1.1.
9. For female patients of childbearing potential and male patients with partners of childbearing potential randomized to the treatment arm: agreement (by patient and/or partner) to remain abstinent (refrain from heterosexual intercourse) or to use highly effective form(s) of contraceptive methods that result in a failure rate of < 1% per year when used consistently and correctly during the treatment period and for 5 months after the last dose of atezolizumab.
|
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| ExclusionCriteria |
| Details |
1. Active or untreated CNS metastases
2. Uncontrolled tumor-related pain
3. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).
4. NCI CTCAE (v4.0) Grade 3 or higher toxicities due to any prior therapy (e.g., radiotherapy) (excluding alopecia), which have not shown improvement and are strictly considered to interfere with current study medication
5. Pregnant or lactating women, or intending to become pregnant during the study.
6.History of autoimmune disease
7.History of idiopathic pulmonary fibrosis (IPF), organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
8.Known positivity for human immunodeficiency virus (HIV)
9.Known active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or known active hepatitis C
10. Active tuberculosis
11.Severe infections within 4 weeks prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
12.Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina
13. Major surgical procedure other than for diagnosis within 4 weeks prior to randomization or anticipation of need for a major surgical procedure during the course of the study
14. Prior allogeneic bone marrow transplantation or solid organ transplant
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Method of Generating Random Sequence
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Permuted block randomization, fixed |
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Method of Concealment
|
Not Applicable |
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Blinding/Masking
|
Not Applicable |
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Primary Outcome
|
| Outcome |
TimePoints |
| The primary objective for this study is to evaluate the efficacy of atezolizumab compared with single agent chemotherapy in patients with treatment-naïve locally advanced or metastatic NSCLC who are deemed unsuitable for platinum-containing therapy. |
Measured by overall survival (OS). |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
Secondary Efficacy Objectives:
The secondary efficacy objectives for this study are to evaluate the efficacy of atezolizumab compared with single agent chemotherapy as measured by OS rates at 6, 12, 18 and 24 months, antitumor effects as measured by investigator assessed ORR , progression-free survival (PFS) and duration of response (DOR) using RECIST v1.1 |
a) OS at 6, 12, 18 & 24 months.
b) ORR
c) PFS
d) DoR
|
Safety Objectives
To evaluate the safety and tolerability of atezolizumab compared with single agent chemotherapy
|
Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v4.0.
Changes in vital signs, physical findings, and clinical laboratory results during and following study drug administration |
Patient-reported Outcome Objectives:
To evaluate and compare 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 (QLQ LC13)
|
Change from baseline in PROs of lung cancer symptoms, patient functioning, HRQoL as assessed by EORTC QLQ-C30 and its supplementary Lung Cancer module (LC13).
TTD in patient-reported lung cancer symptoms of cough, dyspnea (single-item and multi-item subscales), chest pain, arm/shoulder pain, or fatigue using EORTC QLQ-C30 and QLQ-LC13. |
Exploratory Objectives:
To evaluate the efficacy with respect to antitumor effects as measured by investigator-assessed ORR, PFS, DOR and disease control rates (DCR) according to modified RECIST.
To evaluate the relationship between
- the main efficacy endpoints and tumor tissue PD-L1 expression
- the main efficacy endpoints and exploratory biomarkers in tumor tissue and plasma
- the main efficacy endpoints and the expression of immune markers in PBMCs
|
ORR, PFS, DOR and DCR as determined per modified RECIST v1.1.
Tumor tissue PD-L1 expression
Exploratory biomarkers in tumor tissue and plasma
Expression of immune markers in PBMCs
Utility scores of the EQ-5D-5L questionnaire
|
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Target Sample Size
|
Total Sample Size="441"
Sample Size from India="40"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 3 |
|
Date of First Enrollment (India)
|
15/12/2017 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
25/07/2017 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="4"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Closed to Recruitment of Participants |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
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Publication Details
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None yet |
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
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Brief Summary
|
This is a Phase III, global, multicenter, open-label, randomized, controlled study designed to evaluate the efficacy and safety of atezolizumab compared with a single agent chemotherapy regimen by investigator choice (vinorelbine or gemcitabine) in treatment-naïve patients with locally advanced or metastatic NSCLC who are deemed unsuitable for platinum-containing therapy due to poor performance status (Eastern Cooperative Oncology Group performance status [ECOG PS] of 2-3). However, if patients do not meet this criterion, they may be included if deemed unsuitable for platinum-containing therapy by the investigator due to: a) substantial comorbidities b) contraindication(s) for platinum-based antineoplastic drugs. Eligible patients will be stratified by (a) histologic subtype (non-squamous vs squamous), (b) PD-L1 immunohistochemistry (IHC) status (positive/negative/unknown) and (c) brain metastases (yes/no) and then randomized at a 2:1 ratio to receive either atezolizumab or single agent chemotherapy.
Eligible patients must therefore provide a tumor tissue specimen for central assessment of PD-L1 expression by IHC at a central laboratory. The study will enroll all patients whose tissue is evaluable for PD-L1 analysis, regardless of PD-L1 expression status.
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