Lung cancer clinical study comparing efficacy, safety and immunogenicity of CBT124 (Bevacizumab Candidate Biosimilar) with EU-sourced Avastin®.

Phase 3

Not yet recruiting

• Conditions: non-squamous Non-Small-Cell Lung Cancer (nsNSCLC)

• Registration Number: CTRI/2017/02/007805
• Lead Sponsor: Cipla BioTec Pvt Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-02-20
• Last Update Posted: 2017-04-04

Recruitment & Eligibility

• Status: Not Yet Recruiting
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Adult subjects aged ≥ 18 to 75 years (≥ 18 to 65 years for India) with histologically or cytologically confirmed advanced non-squamous NSCLC.
• Mixed tumors should be categorized according to the predominant histology 2.
• Epidermal growth factor receptor (EGFR) negative (for example, deletion exon 19 or exon 21 point mutation L858R) or wild type mutations 3.
• No Kirsten rat sarcoma viral oncogene homolog (KRAS) and anaplastic lymphoma receptor tyrosine kinase (ALK) positive subjects 4.
• Stage IV (Unresectable recurrent disease or metastatic) NSCLC 5.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Evaluable disease status or measurable tumor 7.
• Life expectancy > 6 months.
• Adequate hepatic, renal, and bone marrow function (alanine aminotransferase [ALT] and aspartate aminotransferase [AST] < 2.5 × upper limit of normal [ULN], or ALT and AST < 5 × ULN, if liver function abnormalities are due to underlying malignancy; total bilirubin ≤ 1.5 × ULN; serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance ≥ 60 mL/min; urine dipstick < 1+ [i.e., 0 or traces]; international normalized ratio (INR) ≤ 1.5, and partial thromboplastin time ≤ ULN; absolute neutrophil count ≥ 1500/mm3; platelet count ≥ 105/mm3; hemoglobin ≥ 9 g/dL).
• Subjects with a 1+ or greater urine dipstick reading should undergo further assessment as per the clinical judgement of the Investigator, including 24 hours urine collection or a laboratory protein/creatinine index in urine (with quantitative protein determination in a full sized sample even if not necessarily a 24 hours collection), as needed.
• Urinary protein should be < 100 mg/24 hours or protein/creatinine index of less than 0.2 mg/mgCreatinine or 15 mg/mmol Creatinine.
• Subjects with pre-existing hypertension must be well controlled on a stable regimen of antihypertensive therapy.
• Have systolic blood pressure ≤ 140 and ≥ 90 mmHg, diastolic blood pressure ≤ 90 and ≥ 50 mmHg and heart rate ≥ 40 and ≤ 90 bpm at screening and admission.
• For single measurements in the 141 to 160 mmHg range (systolic) or in the 91 to 100 mmHg range (diastolic), a single repetition after resting for a few minutes (e.g. 5 minutes) on a supine position on the same day is allowed and, in this case, the mean of both measurements will guide eligibility.
• The mean of both the measurements should be ≤ 140 mmHg (systolic) and ≤ 90 mmHg (diastolic).
• Ability to understand risks of participation in the study and willingness provide informed consent.

Exclusion Criteria

• Small cell lung cancer (SCLC) or combination of SCLC and NSCLC.
• Squamous-cell tumors and mixed adenosquamous carcinomas of predominantly squamous nature 2.
• Known sensitizing EGFR mutations (for example, deletion exon 19 or exon 21 point-mutation L858R) or EML4-ALK translocation-positive mutations.
• Subjects with KRAS mutations 3.
• Prior therapy with monoclonal antibodies or small molecule inhibitors against VEGF or VEGF receptors, including bevacizumab 4.
• Prior therapy with carboplatin or paclitaxel 5.
• Prior systemic therapy for metastatic disease.
• Prior systemic anticancer therapy or radiotherapy for locally-advanced NSCLC if completed < 12 months prior to screening 6.
• Evidence of a tumor that compresses or invades major blood vessels or tumor cavitation that in the opinion of the Investigator is likely to bleed 7.
• Symptomatic brain metastasis (head computed tomography [CT]/magnetic resonance imaging [MRI] is required within 6 weeks of study randomization) 8.
• Any unresolved toxicity > Common Toxicity Criteria Grade 1 (except alopecia) from previous anticancer therapy (including radiotherapy) 10.
• History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding.
• Thrombotic or hemorrhagic event ≤ 6 months prior to screening 11.
• History of hemoptysis greater than ½ teaspoon of bright red (fresh) blood in the past 4 weeks 12.
• Subjects receiving long-term aspirin (> 325 mg/day), or other non-steroidal anti-inflammatory agents, or other drugs known to inhibit platelet function, treatment with dipyridamole, ticlopidine, or clopidogrel 13.
• Subjects receiving anticoagulants 14.
• Subjects who plan to undergo surgery during the study period 15.
• Subjects who have undergone a major surgery, or have had a significant traumatic injury within 4 weeks prior to randomization 16.
• Subjects who have a significant non-healing wound, or bone fracture within 4 weeks prior to randomization 17.
• Subjects with history of gastrointestinal perforation or fistula formation 18.
• Female subjects who are pregnant, breast-feeding, planning to be pregnant during the study, or women of child-bearing potential (any woman who is not surgically sterile i.e., bilateral tubal ligation, total hysterectomy or < 2 years post menopause) not using a reliable method of double contraception (e.g. condom plus diaphragm, condom or diaphragm plus spermicidal gel/foam, tubal ligation, or stable dose of hormonal contraception) throughout the study period 20.
• Male subject with a partner of childbearing potential (as mentioned in exclusion criteria 19) who does not consent to the use of a reliable method of double contraception (as mentioned in exclusion criteria 19) 21.
• Subjects with uncontrolled hypertension 22.
• Subjects with active infection assessed to be clinically significant by Investigator 23.
• Known history of, or positive test result for human immunodeficiency virus (HIV), hepatitis C virus (test for hepatitis C virus antibody [HCVAb]) or hepatitis B virus (test for Hepatitis B surface Antigen [HBsAg]) 24.
• History of alcohol or substance abuse 25.
• Prior treatment with any investigational drug within the 30 days prior to screening, or within 5 half-lives of the drug, whichever is longer 26.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) per RECIST criteria version 1.1.Objective response rate is defined as the proportion of subjects whose best confirmed overall	19 Weeks
response over Week 1 to Week 19 is either complete response (CR) or partial response (PR).	19 Weeks
Confirmed best overall response (complete or partial response) may be claimed only if the	19 Weeks
criteria for each are met after a repeat radiologic tumor assessment (using RECIST criteria	19 Weeks
version 1.1) 6 weeks later.	19 Weeks

Secondary Outcome Measures

Name	Time	Method
Efficacy: Progression-free survival (PFS) rate	Overall Survival (OS) rate
Pharmacokinetics: Secondary PK parameters	Cycle 1 (Cmax)
Safety (Proportion of subjects with selected adverse events (AE) of gastrointestinal perforation, hypertension, proteinuria, and pulmonary hemorrhage)	19 weeks and EoS

Trial Locations

Locations (21)

Acharya Tulsi Regional Cancer Treatment & Research Institute; 🇮🇳 Bikaner, RAJASTHAN, India

All India Institute Of Medical Sciences; 🇮🇳 Raipur, CHHATTISGARH, India

All Indian Institute of Medical Sciences (AIIMS); 🇮🇳 Delhi, DELHI, India

Amrita Enterprises and Pvt Ltd.; 🇮🇳 Ernakulam, KERALA, India

Artemis Hospital; 🇮🇳 Gurgaon, HARYANA, India

B. J. Govt. Medical College and Sassoon General Hospital; 🇮🇳 Pune, MAHARASHTRA, India

City Cancer Centre; 🇮🇳 Krishna, ANDHRA PRADESH, India

Curie Manavata Cancer Centre; 🇮🇳 Nashik, MAHARASHTRA, India

Dayanand Medical College & Hospital (DMCH),; 🇮🇳 Ludhiana, PUNJAB, India

Deenanath Mangeshkar Hospital & Research Center; 🇮🇳 Pune, MAHARASHTRA, India

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Acharya Tulsi Regional Cancer Treatment & Research Institute

🇮🇳Bikaner, RAJASTHAN, India

Dr SatyanarayanDr Neeti Sharma

Principal investigator

9782300231

neetisharma@rediffmail.com