Biosimilar Study on Lung Cancer

• Register: CTRI
• Last refreshed on: 24 November 2021
• Main ID: CTRI/2016/06/007041
• Date of registration: 27-06-2016
• Prospective Registration: Yes
• Primary sponsor: Boehringer Ingelheim India Pvt Ltd
• Public title: Biosimilar Study on Lung Cancer
• Scientific title: 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
• Date of first enrolment: 07-10-2016
• Target sample size: 660
• Recruitment status: Suspended
• URL: http://www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=14136
• Study type: Interventional
• Study design: Randomized, Parallel Group, Active Controlled Trial; Method of generating randomization sequence:Computer generated randomization Method of allocation concealment:Centralized Blinding and masking:Participant and Investigator Blinded
• Phase: Phase 3

Countries of recruitment

Argentina, Brazil, Bulgaria, Chile, Croatia, Egypt, Germany, Greece, Hungary, India, Indonesia, 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

Contacts

• Name: Dr Partha Gokhale
• Affiliation: Boehringer Ingelheim India Pvt Ltd

• Name: Dr Partha Gokhale
• Affiliation: Boehringer Ingelheim India Pvt Ltd

Key inclusion & exclusion criteria

Inclusion criteria: 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.
Exclusion criteria: 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 investigatorâ??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 investigatorâ??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

Age minimum:
Age maximum:
Gender:

Health Condition(s) or Problem(s) studied

Health Condition 1: null- Non-Squamous Non-Small Cell Lung Cancer

Intervention(s)

Intervention1: BI 695502; Biosimilar to Avastin.: IV Administration available in two doses (100mg/kg and 400mg/kg)
Control Intervention1: Avastin: IV Administration available in two doses (100mg/kg and 400mg/kg)

Primary Outcome(s)

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®.Timepoint: 18 weeks

Secondary Outcome(s)

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®.Timepoint: End of Trial

Secondary ID(s)

1302.5 version 4.0 dated 19 Feb 2016

Source(s) of Monetary Support

Boehringer Ingelheim

Secondary Sponsor(s)

Quintiles Research India Pvt Ltd

Ethics review

Status: Approved
Approval date: 16/01/2016
Contact:

Ethical Committee

Status: Approved
Approval date: 23/01/2016
Contact:

Nirmal Hospital Private Ethics Committee

Status: Approved
Approval date: 03/02/2016
Contact:

Institutional Ethics Committee

Status: Not Approved
Approval date:
Contact:

Action Cancer Hospital Ethics Committee

Status: Not Approved
Approval date:
Contact:

Apple Hospital Ethics Committee

Status: Not Approved
Approval date:
Contact:

Ethics Committee All India Institute of Medical Sciences

Status: Not Approved
Approval date:
Contact:

Human Ethics Committee

Status: Not Approved
Approval date:
Contact:

Institutional Ethics Committee

Status: Not Approved
Approval date:
Contact:

IPGME&R Research Oversight Committee