Biosimilar Study on Lung Cancer

Phase 3

Suspended

• Conditions: Non-Squamous Non-Small Cell Lung Cancer

• Registration Number: CTRI/2016/06/007041
• Lead Sponsor: Boehringer Ingelheim India Pvt Ltd

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-07-10
• Last Update Posted: 2016-12-30

Recruitment & Eligibility

• Status: Suspended
• Sex: All
• Target Recruitment: 660

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.
• Absolute neutrophil count more than 1.5 x109/L.
• Platelet count more than 100 x109/L.
• 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.
• 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.
• International normalized ratio and partial thromboplastin time within normal limits.
• 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.
• Life expectancy more than 6 months based on clinical judgment.
• 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

• Prior therapy with monoclonal antibodies or small molecule inhibitors against VEGF or VEGF receptors, including Avastin®.
• 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.
• 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.
• Symptomatic brain metastasis.
• Diagnosis of small cell carcinoma of the lung, squamous cell carcinoma of the lung, NSCLC NS (not specified) or NSCLC NOS (not otherwise specified).
• Patients with tumor/metastases cavitation, or invading into large blood vessels.
• Patients with tumor/metastases close to large blood vessels that may have an increased risk of bleeding, according to investigator’s judgment.
• Any unresolved toxicity >Common Toxicity Criteria Grade 1 (except alopecia) from previous anticancer therapy (including radiotherapy).
• History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding.
• Clinically non-significant minor bleeding is acceptable.
• 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).
• 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.
• 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.
• 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.
• 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.
• Live/attenuated vaccine within 12 weeks prior to the Screening Visit.
• 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.
• 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.
• Any surgical procedure within 28 days prior to the first dose of BI 695502/US-licensed Avastin® or anticipated elective surgery during the trial.
• History of active gastroduodenal ulcer(s).
• History of abdominal fistula as well as non-GI fistula, GI perforation or intra-abdominal abscess within 6 months prior to Screening.
• 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.
• 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.
• 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).
• Pregnant or lactating women.
• Known hypersensitivity to any of the trial drugs or their excipients.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The primary objective of this trial is to establish statistical equivalence in terms of	18 weeks
with BI 695502 plus chemotherapy versus United States (US)-licensed Avastin®	18 weeks
plus chemotherapy followed by maintenance monotherapy with either BI 695502	18 weeks
or US-licensed Avastin®.	18 weeks
efficacy (best overall response rate [ORR], proportion of patients with complete	18 weeks
response [CR] plus partial response [PR]) until 18 weeks of first-line treatment	18 weeks

Secondary Outcome Measures

Name	Time	Method
The secondary objectives of the trial are to evaluate further efficacy parameters	(progression-free survival [PFS], overall survival [OS], duration of response) and

Trial Locations

Locations (11)

Action Cancer Hospital; 🇮🇳 Delhi, DELHI, India

All India Institute of Medical Sciences, Bhubaneshwar; 🇮🇳 Khordha, ORISSA, India

Apple Hospital; 🇮🇳 Surat, GUJARAT, India

Aster Medcity, Aster DM Healthcare Pvt Ltd.; 🇮🇳 Ernakulam, KERALA, India

B.P. Poddar Hospital & Medical Research Ltd.; 🇮🇳 Kolkata, WEST BENGAL, India

Basvatarakam Indo-American Cancer Hospital & Research Institute; 🇮🇳 Hyderabad, ANDHRA PRADESH, India

Government Medical College; 🇮🇳 Kozhikode, KERALA, India

Institute of Post graduate medical Education and Research; 🇮🇳 Kolkata, WEST BENGAL, India

Max Super speciality Hospital; 🇮🇳 Delhi, DELHI, India

Nirmal Hospital Private Pvt Ltd; 🇮🇳 Surat, GUJARAT, India

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Action Cancer Hospital

🇮🇳Delhi, DELHI, India

Dr Anish Maru

Principal investigator

91-9811254969

anishmaru@yahoo.com