A Safety and Efficacy Study of BCD-021 With Paclitaxel and Carboplatin Compared to Avastin With Paclitaxel and Carboplatin in Non-Small Cell Lung Cancer

Non-small Cell Lung Cancer Clinical Trial

Official title:

International Multicenter Randomized Double Blind Phase III Trial Comparing Safety and Efficacy of BCD-021 (CJSC BIOCAD, Russia) and Paclitaxel + Carboplatin to Avastin® (F. Hoffmann-La Roche Ltd, Switzerland) and Paclitaxel + Carboplatin in Inoperable or Advanced Non-squamous Non-small-cell Lung Cancer (NSCLC) Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01763645
• Other study ID #: BCD-021-02
• Status: Completed
• Phase: Phase 3
• Start date: October 2012
• Est. completion date: November 2014

Study information

• Verified date: April 2023
• Source: Biocad
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

BCD-021-02 is a double-blind randomized clinical trial comparing efficacy of BCD-021 (INN: bevacizumab) and paclitaxel + carboplatin to Avastin and paclitaxel + carboplatin in inoperable or advanced non-squamous NSCLC patients with pharmacokinetics substudy. The purpose of the study is to demonstrate the non-inferiority of efficacy and safety of BCD-021 compared to Avastin. Also study includes pharmacokinetics assessment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 353
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Written informed consent;

• Newly diagnosed histologically or cytologically confirmed NSCLC excluding squamous NSCLC (mixed cancer types should be classified according to the prevalent cell type);

• IIIb or IV stage of NSCLC (TNM classification version 6);

• Age = 18 years and age = 75 years (both inclusive);

• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2, (not declining within 2 weeks prior to the first dose of investigational product);

• Life expectancy - 12 weeks or more from the moment of randomization;

• Presence of at least 1 measurable tumour with a size not less than 1 cm (revealed with CT slice thickness not more than 5 mm), as defined by modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria (specifically, no ascites, pleural, or pericardial effusions, osteoblastic bone metastases, or carcinomatous lymphangitis of the lung as only lesion;

• Patients should be able to follow the Protocol procedures (according to Investigator's assessment);

• Patients must implement reliable contraceptive measures during all the study treatment, starting 4 weeks prior to the administration of the first dose of investigational product until 6 months after the last dose of investigational product. This requirement does not apply to participants who have undergone surgical sterilization, or patients who are postmenopausal (documented) for the past 2 years. Reliable contraceptive measures include two methods of contraception, including one barrier method

Exclusion Criteria:

• Squamous NSCLC;

• Proven coagulopathy, clinically significant hemorrhage in the past including nasal hemorrhage;

• absolute neutrophil count <1500/mm3;

• Platelets <100 000/mm3;

• Hemoglobin < 90 g/L;

• Creatinine level =1.5 mg/dL;

• Bilirubin level =1.5 × upper limit of normal (ULN);

• Aspartate-aminotransferase(AST) and alanine-aminotransferase (ALT) levels =2.5 × ULN (=5 × ULN for patients with liver metastases);

• Alkaline phosphatase level =5 × ULN;

• Current therapeutic anticoagulation treatment, aspirin (more than 325 mg/day), nonsteroidal anti-inflammatory drugs, antiplatelet agents or protracted treatment with these drugs less than 1 month before entering the study;

• Uncontrolled hypertension comprising all cases of arterial hypertension when no decrease in blood pressure could be achieved despite treatment with a combination of 3 antihypertensive drugs including one diuretic and non-medical correction methods (low salt diet, physical exercise);

• Any previous anticancer therapy (chemotherapy, radiation therapy , surgery etc.) of metastatic NSCLC;

• Radiation or hormone therapy within 21 days prior to randomization;

• Major surgery 28 days before inclusion into the study;

• Previous antiangiogenic therapy;

• Hypersensitivity to taxanes, platinum agents, recombinant murine proteins, contrast agents, premedication agents specified by Protocol (dexamethasone, diphenhydramine, ranitidine) or excipients of investigational products;

• NSCLC metastases in central nervous system excluding metastases non-progressing without glucocorticosteroids within 4 weeks before inclusion into the trial;

• Cardiovascular system pathology (CHF stage III-IV according to New York Heart Association (NYHA) classification);

• Pregnancy or lactation;

• Conditions limiting patient's adherence to Protocol requirements (dementia, neurologic or psychiatric disorders, drug addiction, alcoholism and others);

• Stage II-IV neuropathy according to Common Terminology Criteria for Adverse Events (CTCAE) v.4.0;

• Simultaneous participation in other clinical trials, previous participation in other clinical trials within 30 days before entering into the trial, previous participation in the same trial;

• Any other concomitant cancer revealed within 5 years prior to screening, except curatively treated intraductal carcinoma in situ, curatively treated cervical carcinoma in situ or curatively treated basal cell or squamous cell carcinoma;

• Acute or active chronic infections;

• Hepatitis C virus, hepatitis B virus, HIV, or syphilis infections;

• Obstacles in intravenous administration of study drugs

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Bevacizumab
Patients will receive 6 courses of bevacizumab in combination with carboplatin and paclitaxel. Bevacizumab will be administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks (on Day 1 of each cycle).
• Paclitaxel
Paclitaxel will be administered at a dose of 175 mg/m2 as 3 hour intravenous infusion on Day 1 of each 3-week course (6 courses totally)
• Carboplatin
Carboplatin will be administered (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel on Day 1 of each 3-week course (6 courses totally).

Locations

Country	Name	City	State
Belarus	Brest Regional Clinical Dispensary	Brest
Belarus	Gomel Regional Clinical Oncology Dispensary	Gomel
Belarus	Grodno Regional Clinical Hospital	Grodno
Belarus	Vitebsk Regional Clinical Oncology Dispensary	Vitebsk
India	HCG Bangalore Institute of Oncology	Bangalore
India	M.S.Ramaiah Memorial Hospital	Bangalore
India	Narayana Hrudayalaya Hospitals	Bangalore
Russian Federation	Arkhangelsk District Clinical Oncology Dispensary	Arkhangelsk
Russian Federation	Non-governmental Healthcare Institution "Railway Clinical hospital on the Chelyabinsk Station of JSC Russian Railways"	Chelyabinsk
Russian Federation	State-financed Health Institution "Chelyabinsk Region Clinical Oncology Dispansary"	Chelyabinsk
Russian Federation	State Healthcare Facility "Kursk Regional Oncology Dispensary"	Kursk
Russian Federation	Federal State Institution "Moscow Institute of Cancer Research named after P.A. Hertsen" Ministry of Health of Russian Federation	Moscow
Russian Federation	Institution of Russian Academy of Medical Sciences "Russian Cancer Research Center named after N.N. Blokhin"	Moscow
Russian Federation	State Health Institution of Moscow "Moscow City Oncology Hospital #62 of Moscow Board of Health"	Moscow Region
Russian Federation	Murmansk Regional Oncology Dispensary	Murmansk
Russian Federation	Nizhny Novgorod Region State Budgetary Healthcare Facility "Clinical Diagnostics Center"	Nizhny Novgorod
Russian Federation	State Healthcare Facility "Nizhny Novgorod Regional Oncology Dispensary"	Nizhny Novgorod
Russian Federation	City Clinical Hospital ?1	Novosibirsk
Russian Federation	Regional State Health Institution "Orlov Oncology Dispansary"	Orel
Russian Federation	State Health Institution "Region Oncology Dispansary"	Penza
Russian Federation	Perm Region Oncology Dispensary	Perm
Russian Federation	Federal Government Budgetary Institution "Rostov Institute of Cancer Research" of Ministry of Health of Russian Federation	Rostov-on-Don
Russian Federation	Saint Petersburg City Clinical Oncology Center	Saint Petersburg
Russian Federation	State-financed Health Institution "Samara Region Clinical Oncology Dispansary"	Samara
Russian Federation	Oncology Dispensary 2	Sochi
Russian Federation	St. Petersburg Research and Practice Center for Secondary Care in Oncology	St. Petersburg
Russian Federation	St. Petersburg State Medical University n.a. I. P. Pavlov	St. Petersburg
Russian Federation	Military Medical Academy named after S.M. Kirov	St.Petersburg
Russian Federation	N.N.Petrov Oncology Research Center	St.Petersburg
Russian Federation	Russian scientific center of radiology and surgery technologies	St.Petersburg
Russian Federation	State-financed Health Institution "Stavropol Region Clinical Oncology Dispansary"	Stavropol
Russian Federation	Volgograd District Oncology Dispensary ?1	Volgograd
Russian Federation	Volgograd Regional Oncology Dispensary ?3	Volgograd
Russian Federation	State Health Institution "Voronezh Region Clinical Oncology Dispansary"	Voronezh
Ukraine	Donetsk City Oncology Dispensary	Donetsk
Ukraine	Donetsk Regional Antitumor Center	Donetsk
Ukraine	Kharkiv Regional Clinical Oncology Center	Kharkiv
Ukraine	Kryvyi Rih Oncology Dispensary	Kryvyi Rih
Ukraine	Lviv State Regional Cancer Diagnostic and Treatment Center	Lviv
Ukraine	City Hospital ? 2	Makiivka
Ukraine	Poltava Regional Clinical Oncology Dispensary	Poltava
Ukraine	Zakarpatskyi Clinical Oncology Dispensary	Uzhhorod
Ukraine	Vinnytsia Regional Clinical Oncology Dispensary	Vinnytsia
Ukraine	Zaporizhia Regional Clinical Oncology Dispensary	Zaporizhia

Sponsors (1)

Lead Sponsor	Collaborator
Biocad

Countries where clinical trial is conducted

Belarus,  India,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Day 127
Primary	Area Under the Curve After the First Test Drug Administration	primary outcome measure for pharmacokinetics (PK) substudy	up to Day 22, after the first bevacizumab administration (time points for blood samples: 0 h 1.5 h, 3 h, 4.5 h, 6 h, 24 h, 96 h, 168 h, 336 h and 504 h)
Secondary	Complete Response Rate	secondary outcome measure for efficacy evaluation	Day 127
Secondary	Partial Response Rate	secondary outcome measure for efficacy evaluation	Day 127
Secondary	Stabilization Rate	secondary outcome measure for efficacy evaluation	Day 127
Secondary	Progression Rate	secondary outcome measure for efficacy evaluation	Day 127
Secondary	Occurrence of Anti-bevacizumab Antibodies	Secondary outcome measure for immunogenicity assessment	Day 1 (before the drug administration), Day 15, 64 and 127

External Links

•   Stroyakovskiy, D.L., Fadeeva, N.V., Matrosova, M.P. et al. Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-021 with reference bevacizumab. BMC Cancer 22, 129 (2022). https://doi.org/10.1186/s12885-022-09243-7