| CTRI Number |
CTRI/2016/06/007041 [Registered on: 27/06/2016] Trial Registered Prospectively |
| Last Modified On: |
30/12/2016 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Biological |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
Biosimilar Study on Lung Cancer |
|
Scientific Title of Study
|
A multicenter, randomized, double-blind Phase III trial to evaluate
efficacy and safety of BI 695502 plus chemotherapy versus Avastin®
plus chemotherapy in patients with advanced nonsquamous Non-Small
Cell Lung Cancer |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| 1302.5 version 4.0 dated 19 Feb 2016 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Sumedh Bondal |
| Designation |
Project Manager |
| Affiliation |
Boehringer Ingelheim India Pvt Ltd |
| Address |
Boehringer Ingelheim India Pvt Ltd. 1102, Hallmark Business Plaza, Near Gurunanak Hospital, Gurunanak Hospital Road, Bandra East, Mumbai
Mumbai
MAHARASHTRA
400051
India |
| Phone |
919769419237 |
| Fax |
912226456163 |
| Email |
sumedh.bondal@boehringer-ingelheim.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Partha Gokhale |
| Designation |
Head Clinical Operations |
| Affiliation |
Boehringer Ingelheim India Pvt Ltd |
| Address |
Boehringer Ingelheim India Pvt Ltd. 1102, Hallmark Business Plaza, Near Gurunanak Hospital, Gurunanak Hospital Road, Bandra East, Mumbai
Mumbai
MAHARASHTRA
400051
India |
| Phone |
919769045215 |
| Fax |
912226456163 |
| Email |
partha.gokhale@boehringer-ingelheim.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Partha Gokhale |
| Designation |
Head Clinical Operations |
| Affiliation |
Boehringer Ingelheim India Pvt Ltd |
| Address |
Boehringer Ingelheim India Pvt Ltd. 1102, Hallmark Business Plaza, Near Gurunanak Hospital, Gurunanak Hospital Road, Bandra East, Mumbai
MAHARASHTRA
400051
India |
| Phone |
919769045215 |
| Fax |
912226456163 |
| Email |
partha.gokhale@boehringer-ingelheim.com |
|
|
Source of Monetary or Material Support
|
|
|
Primary Sponsor
|
| Name |
Boehringer Ingelheim India Pvt Ltd |
| Address |
1102, Hallmark Business Plaza, Near Gurunanak Hospital, Gurunanak Hospital Road, Bandra East, Mumbai-400051 |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Quintiles Research India Pvt Ltd |
|
|
|
Countries of Recruitment
|
Argentina
Brazil
Bulgaria
Chile
Croatia
Egypt
Germany
Greece
Hungary
Italy
Japan
Malaysia
Mexico
Philippines
Poland
Portugal
Republic of Korea
Romania
Russian Federation
Serbia
South Africa
Spain
Thailand
Turkey
Ukraine
United Kingdom
United States of America
Viet Nam
India
Indonesia |
|
Sites of Study
|
| No of Sites = 11 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Anish Maru |
Action Cancer Hospital |
Department of Medical Oncology A-4, Paschim Vihar, New Delhi- 110063
New Delhi
DELHI |
91-9811254969
anishmaru@yahoo.com |
| Dr Dillip Kumar Parida |
All India Institute of Medical Sciences, Bhubaneshwar |
Department of Radiation Oncology, Village Sijua, Patrapada, PO Dumduma, Bhubaneshwar-751019, Odisha, India
Khordha
ORISSA |
91-9438884060
drdkparida@gmail.com |
| Dr Patel Jayantilal Govindji |
Apple Hospital |
Department of Oncology, Udhna Darwaja, Ring Road, Surat – 395002, Gujarat, India
Surat
GUJARAT |
91-9825121347
pateldrjayanti@gmail.com |
| Dr Vivek S Radhakrishnan |
Aster Medcity, Aster DM Healthcare Pvt Ltd. |
Department of Oncology, Kuttisahib Road, Near Kothad Bridge,
South Chittoor P.O, Cheranalloor, Kochi 682027, Kerala, India
Ernakulam
KERALA |
91-9731130444
drvivek.radhakrishnan@dmhealthcare.com |
| Dr Chanchal Goswami |
B.P. Poddar Hospital & Medical Research Ltd. |
Department of Medical Oncology, 71/1 Humayun Kabir Sarani, Block – G, New Alipore, Kolkata – 700053, India
Kolkata
WEST BENGAL |
91-9830055035
drcgoswami@gmail.com |
| Dr Ayyagari Santa |
Basvatarakam Indo-American Cancer Hospital & Research Institute |
Department of Medical Oncology, Road No. 14, Banjara Hills, Hyderabad 500034, Andhra Pradesh, India
Hyderabad
ANDHRA PRADESH |
91-9848125174
santa_a2002@yahoo.com |
| Dr Abdul Majeed K |
Government Medical College |
Department of General Medicine, Kozhikode, Calicut-673008, Kerala
Kozhikode
KERALA |
91-9447311247
majeedonco@gmail.com |
| Dr Koushik Chatterjee |
Institute of Post graduate medical Education and Research |
Department of Radiotherapy, 244 J.C Bose Road, Kolkata -700020
Kolkata
WEST BENGAL |
91-9874357580
drkoushik.chatterjee@gmail.com |
| Dr Meenu Walia |
Max Super speciality Hospital |
Department of Medical Oncology, Patparganj
108 A, Indraprastha Extension Patparganj, New Delhi 110 092.
New Delhi
DELHI |
91-9818994001
meenu.walia@maxhealthcare.com |
| Dr Patel Kaushalkumar Babubhai |
Nirmal Hospital Private Pvt Ltd |
Department of Oncology, Ring Road, Surat 395002
Surat
GUJARAT |
91-9723431102
drkaushalbpatel@gmail.com |
| Dr CD Sivanandan |
Regional Cancer Centre |
Department of Radiation Oncology Regional Cancer Centre  PO Box No. 2417 Medical College Campus Thiruvananthpuram 695011 Kerala
Thiruvananthapuram
KERALA |
91-9447882149
sivanandancd@hotmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 12 |
| Name of Committee |
Approval Status |
| Action Cancer Hospital Ethics Committee |
Submittted/Under Review |
| Apple Hospital Ethics Committee |
Submittted/Under Review |
| Ethical Committee |
Approved |
| Ethics Committee All India Institute of Medical Sciences |
Submittted/Under Review |
| Human Ethics Committee |
Submittted/Under Review |
| Institutional Ethics Committee |
Approved |
| Institutional Ethics Committee |
Submittted/Under Review |
| Institutional Ethics Committee |
Submittted/Under Review |
| Institutional Ethics Committee |
Submittted/Under Review |
| Institutional Ethics Committee |
Submittted/Under Review |
| IPGME&R Research Oversight Committee |
Submittted/Under Review |
| Nirmal Hospital Private Ethics Committee |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
Non-Squamous Non-Small Cell Lung Cancer, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
Avastin |
IV Administration available in two doses (100mg/kg and 400mg/kg) |
| Intervention |
BI 695502; Biosimilar to Avastin. |
IV Administration available in two doses (100mg/kg and 400mg/kg) |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
Males and females aged more than equal to 18 years, for Japan only Age more than equal to 20 years at Visit 1, with histologically or cytologically confirmed nsNSCLC. Mixed tumors should be categorized according to the predominant histology.
Recurrent or metastatic disease Stage IV with an indication for therapy with paclitaxel + carboplatin + Avastin®.
All patients must sign and date an Informed Consent Form consistent with ICH GCP
guidelines and local legislation prior to participation in the trial i.e., prior to any trial procedures, which include medication washout and restrictions and be willing to
follow the CTP.
Patients harboring tumors without activating EGFR mutation. Patients with unknown or activating EGFR mutation may be included provided chemotherapy is the site standard of care.
Patients harboring tumors without activating ALK mutation. Patients with unknown or activating ALK mutation may be included provided chemotherapy is the site standard of care.
At least one measurable lesion according to RECIST 1.1 based on independent central review.
ECOG PS 0 or 1.
Adequate hepatic, renal, and bone marrow function
a. Serum creatinine less than equal to 1.5 x upper limit of normal ULN or a creatinine clearance of more than equal to 50 mL/min calculated by Cockroft-Gault formula.
b. Absolute neutrophil count more than 1.5 x109/L.
c. Platelet count more than 100 x109/L.
d. Hemoglobin more than equal to 9 g/dL without transfusion within 2 weeks prior to
randomization.
e.Alanine aminotransferase ALT or aspartate aminotransferase AST less than equal to 2.5 x
ULN. If liver metastases are present, ALT or AST less than equal to 5 x ULN.
f. Alkaline phosphatase less than equal to 2.5 x ULN less than equal to 5 x ULN in the presence of hepatic and/or bone metastases.
g.Serum bilirubin less than equal to 1.5 x ULN, except in the case of known Gilberts syndrome.
h. International normalized ratio and partial thromboplastin time within normal limits.
i. Proteinuria less than 2 g in 24 hours or an equivalent protein/creatinine ratio of
less than 2000 mg/g creatinine or less than 226.0 mg/mmol creatinine.
9. Life expectancy more than 6 months based on clinical judgment.
10. For participants of reproductive potential (males and females), use of a medically
acceptable method of contraception during the trial, i.e., a combination of two forms
of effective contraception (defined as hormonal contraception, intrauterine device,
condom with spermicide, etc). All subjects (males and females of childbearing
potential) must also agree to use an acceptable method of contraception (see above)
for 6 months following completion or discontinuation from the trial medication.
Females will be defined as of childbearing potential if they have not undergone a
permanent contraceptive operation or they are not postmenopausal. Permanent contraceptive operation is defined as: hysterectomy, hysterosalpingectomy, or bilateral oophorectomy. The status of a female should be considered as postmenopausal when she has not had a period for 12 consecutive months without an alternative medical cause. |
|
| ExclusionCriteria |
| Details |
1. Prior therapy with monoclonal antibodies or small molecule inhibitors against VEGF or VEGF receptors, including Avastin®.
2. Prior systemic therapy for metastatic disease.
3.Prior systemic anticancer therapy or radiotherapy for locally advanced nsNSCLC if
completed <12 months prior to Screening.
4.Patients who have results pending for EGFR/ALK mutation status, to the investigator’s knowledge.
5. Previous malignancy other than NSCLC in the last 5 years except for basal cell cancer of the skin or pre-invasive cancer of the cervix.
6. Symptomatic brain metastasis.
7. Diagnosis of small cell carcinoma of the lung, squamous cell carcinoma of the lung,
NSCLC NS (not specified) or NSCLC NOS (not otherwise specified).
8. Patients with tumor/metastases cavitation, or invading into large blood vessels.
9. Patients with tumor/metastases close to large blood vessels that may have an increased risk of bleeding, according to investigator’s judgment.
10. Any unresolved toxicity >Common Toxicity Criteria Grade 1 (except alopecia) from
previous anticancer therapy (including radiotherapy).
11. History or evidence of inherited bleeding diathesis or coagulopathy with the risk of
bleeding. Clinically non-significant minor bleeding is acceptable.
12. A thrombotic or hemorrhagic event ≤6 months prior to Screening (includes
hemoptysis, GI bleeding, hematemesis, central nervous system hemorrhage, epistaxis, vaginal bleeding, cerebral infarction, transient ischemic attacks, myocardial infarction, angina, and coronary artery disease).
13. Current or recent (within 10 days of first dose of BI 695502/US-licensed Avastin®)
regular use of aspirin (>325 mg/day) or other non-steroidal anti-inflammatory drugs (NSAIDs) with antiplatelet activity or treatment with dipyramidole, ticlopidine, clopidogrel or cilostazol.
14. Current treatment with oral, inhaled or topical corticosteroids; the dose must not
exceed 10 mg/day prednisolone or equivalent. During the 4 weeks prior to Day 1, the
dose must be stable.
15. Intravenous, intramuscular, intra-articular, or parenteral corticosteroids within
6 weeks prior to Day 1 or throughout the trial, unless used for paclitaxel infusion premedication, according to regular institutional practice.
16. Current or recent (within 10 days of first dose of BI 695502/US-licensed Avastin®)
use of full-dose oral or parenteral anticoagulants or other thrombolytic agents for
therapeutic (as opposed to prophylactic) purposes, clinically serious (as judged by the
investigator) nonhealing wounds, or incompletely healed bone fracture.
17. Live/attenuated vaccine within 12 weeks prior to the Screening Visit.
18. History of myocardial infarction (≤6 months prior to Screening), unstable angina, New York Heart Association Grade II or greater, congestive heart failure, or serious cardiac arrhythmia requiring medication.
19. Patients with a history of poorly controlled hypertension or with resting blood
pressure >150/100 mmHg in the presence or absence of a stable regimen of
antihypertensive therapy.
20. Any surgical procedure within 28 days prior to the first dose of BI 695502/US-licensed Avastin® or anticipated elective surgery during the trial.
21. History of active gastroduodenal ulcer(s).
22. History of abdominal fistula as well as non-GI fistula, GI perforation or intra-abdominal abscess within 6 months prior to Screening.
23. Active or chronic hepatitis B or C, ongoing human immunodeficiency virus (HIV) infection, or tuberculosis (TB). Screening for HIV and TB to be performed according to local practice and local regulatory guidance.
24. Treatment within a clinical trial within 4 weeks prior to initiation of trial treatment.
Patients who have received treatment with a drug that has not received regulatory approval for any indication within 4 weeks or a minimum of 5 half-lives, whichever is longer, of the initial dose of trial medication.
25. Patient considered unsuitable for inclusion by the investigator (e.g., inability to
understand and/or comply with study requirements or presence of any condition which, in the opinion of the investigator, would not allow safe participation in the
trial).
26. Pregnant or lactating women.
27. Known hypersensitivity to any of the trial drugs or their excipients. |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Participant and Investigator Blinded |
|
Primary Outcome
|
| Outcome |
TimePoints |
The primary objective of this trial is to establish statistical equivalence in terms of
efficacy (best overall response rate [ORR], proportion of patients with complete
response [CR] plus partial response [PR]) until 18 weeks of first-line treatment
with BI 695502 plus chemotherapy versus United States (US)-licensed Avastin®
plus chemotherapy followed by maintenance monotherapy with either BI 695502
or US-licensed Avastin®. |
18 weeks |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
The secondary objectives of the trial are to evaluate further efficacy parameters
(progression-free survival [PFS], overall survival [OS], duration of response) and
the safety and tolerability of BI 695502 versus US-licensed Avastin®. |
End of Trial |
|
|
Target Sample Size
|
Total Sample Size="660"
Sample Size from India="60"
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)
|
07/10/2016 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
21/07/2015 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="3"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Suspended |
|
Publication Details
|
|
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
This is a Phase III, randomized, double-blind, multicenter, active comparator, parallel two-arm trial to compare BI 695502 plus paclitaxel and carboplatin (Arm B) versus US-licensed Avastin® plus paclitaxel and carboplatin (Arm A). After 4 to 6 induction cycles are given, all patients who do not have disease progression (i.e., patients with CR, PR or stable disease) will receive maintenance with BI 695502 or US-licensed Avastin® alone, per the original randomization. |