Clinical trial NCT01763645: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer
Keywords: NSCLC
bevacizumab
pharmacokinetics
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2013-01-09
Enrollment: 353
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Overall Response Rate
timeFrame: Day 127
measure: Area Under the Curve After the First Test Drug Administration
timeFrame: 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 outcomes:
measure: Complete Response Rate
timeFrame: Day 127
measure: Partial Response Rate
timeFrame: Day 127
measure: Stabilization Rate
timeFrame: Day 127
measure: Progression Rate
timeFrame: Day 127
measure: Occurrence of Anti-bevacizumab Antibodies
timeFrame: Day 1 (before the drug administration), Day 15, 64 and 127
Other outcomes:
Locations:
city: Brest
country: Belarus
facility: Brest Regional Clinical Dispensary
city: Gomel
country: Belarus
facility: Gomel Regional Clinical Oncology Dispensary
city: Grodno
country: Belarus
facility: Grodno Regional Clinical Hospital
city: Vitebsk
country: Belarus
facility: Vitebsk Regional Clinical Oncology Dispensary
city: Bangalore
country: India
facility: HCG Bangalore Institute of Oncology
city: Bangalore
country: India
facility: M.S.Ramaiah Memorial Hospital
city: Bangalore
country: India
facility: Narayana Hrudayalaya Hospitals
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk District Clinical Oncology Dispensary
city: Chelyabinsk
country: Russian Federation
facility: Non-governmental Healthcare Institution "Railway Clinical hospital on the Chelyabinsk Station of JSC Russian Railways"
city: Chelyabinsk
country: Russian Federation
facility: State-financed Health Institution "Chelyabinsk Region Clinical Oncology Dispansary"
city: Kursk
country: Russian Federation
facility: State Healthcare Facility "Kursk Regional Oncology Dispensary"
city: Moscow Region
country: Russian Federation
facility: State Health Institution of Moscow "Moscow City Oncology Hospital #62 of Moscow Board of Health"
city: Moscow
country: Russian Federation
facility: Institution of Russian Academy of Medical Sciences "Russian Cancer Research Center named after N.N. Blokhin"
city: Moscow
country: Russian Federation
facility: Federal State Institution "Moscow Institute of Cancer Research named after P.A. Hertsen" Ministry of Health of Russian Federation
city: Murmansk
country: Russian Federation
facility: Murmansk Regional Oncology Dispensary
city: Nizhny Novgorod
country: Russian Federation
facility: Nizhny Novgorod Region State Budgetary Healthcare Facility "Clinical Diagnostics Center"
city: Nizhny Novgorod
country: Russian Federation
facility: State Healthcare Facility "Nizhny Novgorod Regional Oncology Dispensary"
city: Novosibirsk
country: Russian Federation
facility: City Clinical Hospital №1
city: Orel
country: Russian Federation
facility: Regional State Health Institution "Orlov Oncology Dispansary"
city: Penza
country: Russian Federation
facility: State Health Institution "Region Oncology Dispansary"
city: Perm
country: Russian Federation
facility: Perm Region Oncology Dispensary
city: Rostov-on-Don
country: Russian Federation
facility: Federal Government Budgetary Institution "Rostov Institute of Cancer Research" of Ministry of Health of Russian Federation
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg City Clinical Oncology Center
city: Samara
country: Russian Federation
facility: State-financed Health Institution "Samara Region Clinical Oncology Dispansary"
city: Sochi
country: Russian Federation
facility: Oncology Dispensary 2
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg State Medical University n.a. I. P. Pavlov
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg Research and Practice Center for Secondary Care in Oncology
city: St.Petersburg
country: Russian Federation
facility: N.N.Petrov Oncology Research Center
city: St.Petersburg
country: Russian Federation
facility: Military Medical Academy named after S.M. Kirov
city: St.Petersburg
country: Russian Federation
facility: Russian scientific center of radiology and surgery technologies
city: Stavropol
country: Russian Federation
facility: State-financed Health Institution "Stavropol Region Clinical Oncology Dispansary"
city: Volgograd
country: Russian Federation
facility: Volgograd District Oncology Dispensary №1
city: Volgograd
country: Russian Federation
facility: Volgograd Regional Oncology Dispensary №3
city: Voronezh
country: Russian Federation
facility: State Health Institution "Voronezh Region Clinical Oncology Dispansary"
city: Donetsk
country: Ukraine
facility: Donetsk City Oncology Dispensary
city: Donetsk
country: Ukraine
facility: Donetsk Regional Antitumor Center
city: Kharkiv
country: Ukraine
facility: Kharkiv Regional Clinical Oncology Center
city: Kryvyi Rih
country: Ukraine
facility: Kryvyi Rih Oncology Dispensary
city: Lviv
country: Ukraine
facility: Lviv State Regional Cancer Diagnostic and Treatment Center
city: Makiivka
country: Ukraine
facility: City Hospital № 2
city: Poltava
country: Ukraine
facility: Poltava Regional Clinical Oncology Dispensary
city: Uzhhorod
country: Ukraine
facility: Zakarpatskyi Clinical Oncology Dispensary
city: Vinnytsia
country: Ukraine
facility: Vinnytsia Regional Clinical Oncology Dispensary
city: Zaporizhia
country: Ukraine
facility: Zaporizhia Regional Clinical Oncology Dispensary
Study officials:
affiliation: Director of Clinical Development Department, BIOCAD
name: Yulia Linkova, MD, PhD
role: STUDY_DIRECTOR
References:
citation: Stroyakovskiy DL, Fadeeva NV, Matrosova MP, Shelepen KG, Adamchuk GA, Roy B, Nagarkar R, Kalloli M, Zhuravleva D, Voevodin GD, Shustova MS, Kryukov F. Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-021 with reference bevacizumab. BMC Cancer. 2022 Feb 1;22(1):129. doi: 10.1186/s12885-022-09243-7.