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Trial details
A Randomized, Multicenter, Multinational, Double-Blind Study to Assess the Efficacy and Safety of MB02 (Bevacizumab Biosimilar Drug) Versus Avastin® in Combination With Carboplatin and Paclitaxel for the Treatment of Subjects With Stage IIIB/IV Non-squamous Non-Small Cell Lung Cancer (NSCLC)
Current status:
Approved
|
Date registered:
17/12/2020
|
Date last updated:
18/11/2020
Trial version(s)
History: 06/11/2018
Current: 06/11/2018
Click here to view the tips and fields' descriptions
Main Information
Primary registry identifying number
LBCTR2018120171
Protocol number
MB02-C-02-17
MOH registration number
2018/2/9597
Trial already registered with the MoPH
Study registered at the country of origin
Type of registration
Retrospective
Type of registration: Justify
LBCTR was not available
Date of registration in national regulatory agency
05/03/2018
Primary sponsor
mAbxience Research S.L.
Primary sponsor: Country of origin
Spain
Public title
A Randomized, Multicenter, Multinational, Double-Blind Study to Assess the Efficacy and Safety of MB02 (Bevacizumab Biosimilar Drug) Versus Avastin® in Combination With Carboplatin and Paclitaxel for the Treatment of Subjects With Stage IIIB/IV Non-squamous Non-Small Cell Lung Cancer (NSCLC)
Acronym
STELLA
Scientific title
A Randomized, Multicenter, Multinational, Double-Blind Study to Assess the Efficacy and Safety of MB02 (Bevacizumab Biosimilar Drug) Versus Avastin® in Combination With Carboplatin and Paclitaxel for the Treatment of Subjects With Stage IIIB/IV Non-squamous Non-Small Cell Lung Cancer (NSCLC)
Acronym
STELLA
Brief summary of the study: English
This is a multicenter, multinational, double-blind, 1:1 randomized, parallel-group, equivalence Phase 3 study to compare the efficacy and safety of MB02 versus Avastin® in subjects with Stage IIIB/IV non-squamous NSCLC in combination with Carboplatin and Paclitaxel. MB02/Avastin® plus chemotherapy will be repeated every 21 days for 6 cycles. After 6 cycles, subjects can continue to receive MB02/Avastin® monotherapy treatment every 3 weeks . Patients will stay on treatment until evidence of disease progression, intolerance or until unacceptable toxic effects develop. The study ends at Week 52; no further study assessments will be made after this time.
Brief summary of the study: Arabic
هذه الدراسة هي دراسة تكافؤ في المرحلة الثالثة وهي متعددة المراكز، متعددة الجنسيات، مزدوجة التعمية، بتوزيع عشوائي بنسبة ١:١، بمجموعتين متوازيتين، والغرض منها مقارنة فعالية وسلامة العقار MB02 بالمقارنة مع العقار أفاستین ® لدى المشاركين المُصابين بسرطان الرئة ذي الخلايا غير الصغيرة وغير الحرشفية (NSCLC) في المرحلة IIIB/IV مع العقارين كاربوبلاتین و باكلیتاكسیل. سيتم تكرار العلاج بواسطة /MB02أفاستین® بالإضافة إلى العلاج الكيميائي كل ٢١ يوم ولـ ٦ دورات. بعد ٦ دورات، بإمكان المشاركين الاستمرار بتلقي العلاج الأحادي بـ /MB02أفاستین ® كل ٣ أسابيع. وسيستمر المرضى على هذا العلاج إلى حين ظهور دليل على تطور المرض أو على عدم تحمل العلاج أو إلى حين تطور آثار سميّة غير مقبولة. وتنتهي الدراسة في الأسبوع رقم ٥٢؛ ولن يتم بعد ذلك الوقت إجراء أي تقييمات خاصة بالدراسة.
Health conditions/problem studied: Specify
Stage IIIB/IV Non-squamous Non-Small Cell Lung Cancer
Interventions: Specify
Cycle 1 through Cycle 6 (Monoclonal Immnuglobulin therapy in combination with chemotherapy administered on Day 1 of every 3 week treatment cycle) - Arm 1: MB02 (bevacizumab biosimilar) IV at an intended dose of 15 mg/ kg Paclitaxel IV at an intended dose of 200 mg/ m2 Carboplatin IV to achieve and AUC 6 - Arm 2: Avastin (bevacizumab) IV at an intended dose of 15 mg/ kg Paclitaxel IV at an intended dose of 200 mg/ m2 Carboplatin IV to achieve and AUC 6 From Cycle 7 onwards (Monoclonal Immnuglobulin monotherapy): Arm 1: MB02 (bevacizumab biosimilar) IV at an intended dose of 15 mg/ kg - Arm 2: Avastin (bevacizumab) IV at an intended dose of 15 mg/ kg
Key inclusion and exclusion criteria: Inclusion criteria
Inclusion Criteria To be eligible for study entry, subjects must satisfy all of the following criteria: 1. Males and female subjects aged ≥ 18 years to ≤ 80 years. 2. Signed informed consent must be obtained before initiation of any study-specific procedures or treatment as confirmation of the subject’s awareness and willingness to comply with the study requirements. 3. Subjects should have newly diagnosed or recurrent Stage IIIB/IV (defined by seventh edition of the TNM classification for Lung Cancer, 2010) non-squamous NSCLC not amenable to curative intent surgery, and not have received any systemic therapy for advanced disease (exclusion criteria 3 and 4). For subjects with recurrent disease, at least 6 months must have elapsed before randomization from previous adjuvant treatment. 4. Previous radiation therapy if completed >4 weeks before randomization. Palliative radiotherapy to bone lesions is allowed if completed >2 weeks of randomization. 5. Subjects must have at least 1 unidimensional measurable lesion per RECIST version 1.1 (assessed locally). 6. Subjects must have an ECOG performance status ≤1 at Screening. 7. Subjects must have adequate hepatic, renal and hematologic function defined as: Hepatic function: bilirubin level <1.5 ULN, ALT and AST levels<2.5×ULN. Renal function: serum creatinine level <1.5×ULN, calculated creatinine clearance (CrCl) >30 mL/min (Cockroft-Gault formula), urine protein to creatinine ratio <1. Subjects with urine protein-to-creatinine ratio >1 may be enrolled if they have <1 g of protein in 24-hour urine collection. Hematological function: Absolute neutrophil count >1.5×109 /L; platelets >100×109 /L, hemoglobin (Hb) >9 g/dL. Adequate coagulation parameters such as: INR ≤ 2.0 and aPTT ≤ 1.5 x ULN within 7 days prior to randomization for patients not receiving anticoagulation therapy. 8. Eligible subjects must have a systolic blood pressure of ≤ 140 mm Hg and a diastolic blood pressure of < 100 mm Hg at screening. 9. Women of childbearing potential, and their partners, must agree to adhere to pregnancy prevention methods throughout the duration of the study (including the Follow-up visits, where applicable). Women of childbearing potential are defined as those who are not surgically sterile (did not underwent bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) and not postmenopausal. Subjects and their partners must agree to use a highly effective method of contraception, to avoid women becoming pregnant throughout the course of the study. Medically acceptable forms of birth control can include the following, with approval of the treating physician: -Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner, sexual abstinence. 10. Non fertile women can be included, that is, those who are physiologically incapable of becoming pregnant, because of: Hysterectomy. Bilateral oophorectomy (ovariectomy). Bilateral tubal ligation or, Postmenopausal women defined as: Subjects not using HRT and have experienced total cessation of menses for 1 year and be greater than 45 years of age, OR, in questionable cases, have a follicle stimulating hormone >40 mIU/mL and an estradiol value <40 pg/mL (<140 pmol/L). Subjects must discontinue HRT before study enrolment because of the potential for inhibition of cytochrome enzymes that metabolize estrogens and progestins. For most forms of HRT, at least 2 to 4 weeks must elapse between the cessation of HRT and determination of menopausal status; the length of this interval depends on the type and dosage of HRT. If a female subject is determined not to be postmenopausal, that subject must use adequate contraception, as defined immediately above (inclusion 8).
Key inclusion and exclusion criteria: Gender
Both
Key inclusion and exclusion criteria: Age minimum
18
Key inclusion and exclusion criteria: Age maximum
80
Key inclusion and exclusion criteria: Exclusion criteria
Exclusion Criteria Subjects will be excluded from the study if 1 or more of the following criteria are applicable: 1. Inability to comply with protocol procedures. 2. Participation in another clinical trial or treatment with another investigational agent within 4 weeks or 5 half-lives of investigational agent before randomization, whichever is longer. 3. Subjects previously treated with monoclonal antibodies or small molecule inhibitors against VEGF or VEGF receptors, including Avastin®. 4. Subjects who have received previous chemotherapy, immunotherapy, targeted therapy, or biological therapy for their lung cancer. Note: Adjuvant and neoadjuvant therapy are permitted (see: inclusion criterion 3). 5. Subjects who have known central nervous system disease, with the exception of subjects with treated brain metastases who have completed treatment (radiation, surgery or stereotactic surgery) and have not received steroids for at least 4 weeks before randomization. Subjects with central nervous system metastases treated by neurosurgical resection or brain biopsy performed within 8 weeks before randomization will be excluded. Subjects with known or history of brain metastases must undergo brain imaging during screening. 6. Current or recent (within 10 days of the first dose of study treatment) use of aspirin (at least 325 mg/day) or other nonsteroidal anti-inflammatory drugs with antiplatelet activity or treatment with dipyridamole (Persantine®), ticlopidine (Ticlid®), clopidogrel (Plavix®), or cilostazol (Pletal®). 7. Current or recent (within 5 days) use of therapeutic anticoagulation or use of thrombolytic agent. Prophylactic use of low molecular weight heparin is allowed. 8. Subjects with an INR >2, unless receiving active anticoagulation treatment, will be excluded. 9. Subjects who have a diagnosis of small cell carcinoma of the lung or squamous cell carcinoma of the lung. Mixed tumors should be categorized according to the predominant histology. If small cell elements are present, the subject will be excluded. 10. Subjects with known tumors that harbor activating epidermal growth factor receptor and anaplastic lymphoma receptor tyrosine kinase (assessed locally). 11. Subjects who have a history of hypersensitivity to the active substance (bevacizumab, carboplatin, and/or paclitaxel) or any of the excipients (such as trehalose dehydrate, sodium phosphate, or polysorbate 20). 12. Subjects with known active viral infection: hepatitis B, hepatitis C, or HIV. 13. Subjects who are pregnant or breastfeeding. Women of child-bearing potential must have a negative pregnancy test at Screening. 14. Subjects with previous major surgery, open biopsy, open pleurodesis, or significant traumatic injury within 4 weeks before randomization or those anticipated to require major surgery during the study. 15. Subjects who have had a core biopsy taken or have had another minor surgical procedure, excluding placement of vascular access device, closed pleurodesis, thoracentesis, and mediastinoscopy, within 1 week of randomization. 16. Subjects with a history of abdominal fistula, GI perforation, intra-abdominal abscess within 6 months of randomization. 17. Subjects with a nonhealing wound, active ulcer, or untreated bone fracture. 18. Subjects with previous history of hypertensive crisis or hypertensive encephalopathy. 19. Subjects with New York Heart Association Grade II or greater congestive heart failure, or angina, myocardial infarction within 6 months before randomization; symptomatic arrhythmia or serious cardiac arrhythmia requiring medication; abnormal left ventricular ejection fraction < 50% assessed by ultrasound or multigated acquisition scan. 20. Subjects with a previous malignancy within 3 years of randomization (other than superficial basal cell and superficial squamous (skin) cell carcinoma, or carcinoma in situ of the uterine cervix, bladder, or prostate). 21. Subjects with history of a significant vascular event within 6 months before randomization (including, but not limited to myocardial infarction and stroke or transient ischemic attack). 22. Subjects with known bleeding diathesis or significant coagulopathy within 3 months before randomization. 23. Subjects with history of grade ≥2 hemoptysis within 6 months before randomization (≥0.5 teaspoons of bright red blood per event). 24. Subjects with a tumor(s) invading or compressing major blood vessels.
Type of Study
Type
Interventional
Type of intervention
Pharmaceutical
Trial scope
Therapy
Trial scope: Specify scope
Study design: Allocation
Randomized controlled trial
Study design: Masking
Blinded (masking used)
Study design: Control
Active
Study phase
3
Study design: Purpose
Treatment
Study design: Assignment
Parallel
IMP has market authorization
No
Name of IMP
MB02
Type of IMP
Others
Type of IMP: Specify
recombinant humanized monoclonal antibody that specifically binds to the human vascular endothelial growth factor
Pharmaceutical class
Monoclonal immunoglobulin G1 antibody
Therapeutic indication
Stage IIIB/IV Non-squamous Non-Small Cell Lung Cancer
Therapeutic benefit
The study population will comprise subjects with Stage IIIB/IV non-squamous NSCLC not amenable to curative intent surgery and, who have not received any systemic therapy for advanced disease.
Biospecimen retention
None retained
Biospecimen description
Hematology, clinical chemistry, coagulation and urine laboratory analyses will be performed at a central laboratory. Blood samples will be taken to determine serum biomarkers (antidrug antibodies) through 52 weeks after first study drug administration. Analysis of immunogenicity endpoints will be conducted by an external provider.
Target sample size
576
Actual enrollment target size
576
Date of first enrollment: Type
Actual
Date of first enrollment: Date
06/02/2018
Date of study closure: Type
Actual
Date of study closure: Date
03/06/2020
Recruitment status
Complete
Date of completion
14/07/2020
IPD sharing statement plan
No
IPD sharing statement description
Not Applicable
Additional data URL
https://clinicaltrials.gov/ct2/show/NCT03296163
Summary Results
Secondary Identifying Numbers
Full name of issuing authority
Secondary identifying number
Sources of Monetary or Material Support
Name
mAbxience
Secondary Sponsors
Name
One sponsor only
Contact for Public/Scientific Queries
Contact type
First name
Last name
Address
Country
Telephone
Email
Affiliation
Public
Dr. Pavel
Tyan
Germany
Germany
+4989993913302
pavel.tyan2@syn
INC Research
Scientific
Dr. Fadi
Farhat
Ghassan Hammoud street, Saida
Lebanon
009613753155
dr.fadi.trials@gmail.com
Hammoud Hospital University Medical Center
Scientific
Dr. Hady
Ghanem
Zahar Street Achrafieh
Lebanon
0096176477647
hady.ghanem@laumcrh.com
Lebanese American University Medical Center- Rizk Hospital
Scientific
Dr. Jawad
Makarem
Ain Wazein, El Chouf
Lebanon
009613484288
jawad.makarem@awmedicalvillage.org
Ain Wazein Medical Village
Scientific
Dr. Paul
Khoueiry
Jbeil
Lebanon
009613887995
drpaulkhoueiry@yahoo.com
Centre Hospitalier Universitaire Notre Dame de Secours
Centers/Hospitals Involved in the Study
Center/Hospital name
Name of principles investigator
Principles investigator speciality
Ethical approval
Hammoud Hospital University Medical Center
Dr. Fadi Farhat
on
Approved
Lebanese American University- University Medical Center Rizk Hospital
Dr. Hady Ghanem
on
Approved
Ain w Zein Medical Village
Dr. Jawad Makarem
on
Approved
Notre Dame des Secours Centre Hospitalier Universitaire
Dr. Paul Khouery
on
Approved
Ethics Review
Ethics approval obtained
Approval date
Contact name
Contact email
Contact phone
Hammoud Hospital University Medical Center
25/09/2017
Ghada Aoun
medical@hammoudhospital.org
009613408947
Lebanese American University- University Medical Center Rizk Hospital
09/01/2018
Christine Chalhoub
christine.chalhoub@lau.edu.lb
009613212 327
Ain w Zein Medical Village
23/12/2017
Hayat Kamaleddine
Hayat Kamaleddine
009613853 017
Notre Dame des Secours Centre Hospitalier Universitaire
19/02/2018
Sally Nassour
dm@chu-nds.org
009619940 413
Countries of Recruitment
Name
Ukraine
Thailand
Republic of Serbia
Russian Federation
Philippines
Mexico
Malaysia
Lebanon
India
Hungary
Greece
Georgia
Chile
Bulgaria
Brazil
Peru
South Africa
Spain
Turkey
Health Conditions or Problems Studied
Condition
Code
Keyword
Stage IIIB/IV Non-squamous Non-Small Cell Lung Cancer
Malignant neoplasm of bronchus and lung (C34)
Lung Cancer
Interventions
Intervention
Description
Keyword
Arm 1
MB02 + Paclitaxel + Carboplatin
MB02
Arm 2
Avastin + Paclitaxel + Carboplatin
Avastin
Primary Outcomes
Name
Time points
Measure
Objective Response Rate
Week 18 after intiation of treatment
Recist 1.1 tumor assessment
Key Secondary Outcomes
Name
Time points
Measure
Safety profile of MB02 compared with Avastin®
During study
NCI-CTCAE; v4.03
Potential immunogenicity of MB02 compared with that of Avastin®
During study
Antidrug antibodies
Progression-free survival and Overall survival
Week 18 and Week 52
Recist 1.1 tumor assessment
Trial Results
Summary results in Lebanon
Study results globally
Date of posting of results summaries
Date of first journal publication of results
Results URL link
Baseline characteristics
Participant flow
Adverse events
Outcome measures
URL to protocol files
Link(s) to publications related to the study
Changes History
Change
Date
Recruitment status updated and date of closure and date of completion and closure entered
Download as PDF
Save a PDF copy of the summary of the trial