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 - Full Text View

Purpose

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.

Condition	Intervention	Phase
Non-small Cell Lung Cancer	Drug: Bevacizumab Drug: Paclitaxel Drug: Carboplatin	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

Genetics Home Reference related topics: lung cancer

MedlinePlus related topics: Lung Cancer

Drug Information available for: Paclitaxel Carboplatin Bevacizumab

U.S. FDA Resources

Further study details as provided by Biocad:

Primary Outcome Measures:

Overall response rate [ Time Frame: Day 127 ] [ Designated as safety issue: No ]
primary outcome measure for efficacy evaluation
Area under the curve after the first test drug administration [ Time Frame: 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) ] [ Designated as safety issue: No ]
primary outcome measure for pharmacokinetics (PK) substudy

Secondary Outcome Measures:

Complete response rate [ Time Frame: Day 127 ] [ Designated as safety issue: No ]
secondary outcome measure for efficacy evaluation
Partial response rate [ Time Frame: Day 127 ] [ Designated as safety issue: No ]
secondary outcome measure for efficacy evaluation
Stabilization rate [ Time Frame: Day 127 ] [ Designated as safety issue: No ]
secondary outcome measure for efficacy evaluation
Progression rate [ Time Frame: Day 127 ] [ Designated as safety issue: No ]
secondary outcome measure for efficacy evaluation
Relative number (%) of chemotherapy cycles, postponed due to adverse events (AE) [ Time Frame: Day 127 ] [ Designated as safety issue: Yes ]
secondary outcome measure for safety evaluation
Treatment discontinuation rate due to AE [ Time Frame: Day 127 ] [ Designated as safety issue: Yes ]
secondary outcome measure for safety evaluation
Occurrence and titer of anti-bevacizumab antibodies [ Time Frame: Day 1 (before the drug administration), Day 15, 64 and 127 ] [ Designated as safety issue: Yes ]
Secondary outcome measure for immunogenicity assessment
Cmax [ Time Frame: Up to Day 22 ] [ Designated as safety issue: No ]
secondary outcome measure for PK substudy
Tmax [ Time Frame: Up to Day 22 ] [ Designated as safety issue: No ]
secondary outcome measure for PK substudy
T1/2 [ Time Frame: Up to Day 22 ] [ Designated as safety issue: No ]
secondary outcome measure for PK substudy
AE incidence and severity [ Time Frame: Up to Day 148 ] [ Designated as safety issue: Yes ]
secondary outcome measure for safety evaluation
AEs grade 3-4 incidence [ Time Frame: Up to Day 148 ] [ Designated as safety issue: Yes ]
secondary outcome measure for safety evaluation
minimal serum bevacizumab concentration [ Time Frame: Day 22, Day 43, Day 64, Day 85, Day 106, Day 127 ] [ Designated as safety issue: No ]
Secondary outcome measure for pharmacokinetics analysis


Estimated Enrollment:	214
Study Start Date:	October 2012
Estimated Study Completion Date:	November 2015
Estimated Primary Completion Date:	November 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: BCD-021 (CISC BIOCAD) BCD-021 is a product code for bevacizumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-021 in combination with carboplatin and paclitaxel. BCD-021 will be administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks (on Day 1 of each course). Paclitaxel will be administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.	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). Other Names: Avastin BCD-021 Drug: 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) Other Name: Taxacad Drug: 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).
Active Comparator: Avastin (F. Hoffmann-La Roche Ltd) In this arm patients will receive 6 courses of treatment with Avastin in combination with carboplatin and paclitaxel. Avastin will be administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks on Day 1. Paclitaxel will be administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.	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). Other Names: Avastin BCD-021 Drug: 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) Other Name: Taxacad Drug: 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).

Arms

Assigned Interventions

Experimental: BCD-021 (CISC BIOCAD)

BCD-021 is a product code for bevacizumab biosimilar manufactured by CJSC BIOCAD, Russia. In this arm patients will receive 6 courses of treatment with BCD-021 in combination with carboplatin and paclitaxel. BCD-021 will be administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks (on Day 1 of each course). Paclitaxel will be administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.

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).

Other Names:

Avastin
BCD-021

Drug: 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)

Other Name: Taxacad

Drug: 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).

Active Comparator: Avastin (F. Hoffmann-La Roche Ltd)

In this arm patients will receive 6 courses of treatment with Avastin in combination with carboplatin and paclitaxel. Avastin will be administered at a dose of 15 mg/kg as 90 min intravenous infusion every 3 weeks on Day 1. Paclitaxel will be administered at a dose of 175 mg/m2 as 3 hour intravenous infusion every 3 weeks on Day 1 and carboplatin (AUC 6 mg/ml×min) as 15 - 30 min intravenous infusion just after paclitaxel every 3 weeks on Day 1.

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).

Other Names:

Avastin
BCD-021

Drug: 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)

Other Name: Taxacad

Drug: 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).

Eligibility


Ages Eligible for Study:	18 Years to 75 Years (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 metastatc 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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01763645

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Sponsors and Collaborators

Biocad

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site


Responsible Party:	Biocad
ClinicalTrials.gov Identifier:	NCT01763645 History of Changes
Other Study ID Numbers:	BCD-021-02
Study First Received:	December 27, 2012
Last Updated:	February 2, 2015
Health Authority:	Russia: Ministry of Health of the Russian Federation

Keywords provided by Biocad:


NSCLC bevacizumab pharmacokinetics

Additional relevant MeSH terms:


Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Paclitaxel Albumin-Bound Paclitaxel Bevacizumab	Carboplatin Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors

ClinicalTrials.gov processed this record on September 28, 2016