Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Evaluation of FKB238 and Avastin in Patients With Advanced/Recurrent Non-squamous Non-small Cell Lung Cancer (AVANA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02810457
Recruitment Status : Active, not recruiting
First Posted : June 23, 2016
Results First Posted : March 19, 2020
Last Update Posted : March 19, 2020
Sponsor:
Information provided by (Responsible Party):
Centus Biotherapeutics Limited

Brief Summary:
The purpose of this research study is to compare the effectiveness and safety of FKB238 against Avastin® in men and women with advanced/recurrent non squamous non-small cell lung cancer

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: FKB238 (bevacizumab) Drug: Avastin (bevacizumab) Drug: Paclitaxel Drug: Carboplatin Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 731 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised, Parallel, Double Blinded Study to Compare the Efficacy and Safety of FKB238 to Avastin® In 1st Line Treatment for Patients With Advanced/Recurrent Non Squamous NSCLC in Combination of Paclitaxel and Carboplatin
Actual Study Start Date : September 7, 2016
Actual Primary Completion Date : January 24, 2019
Estimated Study Completion Date : February 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: FKB238 / paclitaxel / carboplatin

Drug: FKB238:

15 mg/kg IV infusion on Day 1 of each 21-day cycle.

Drug: Paclitaxel:

200 mg/m2 IV infusion on Day 1 of each 21-day cycle for at least 4 and no more than 6 cycles.

Drug: Carboplatin:

Area Under Curve (AUC) = 6.0 IV infusion on Day 1 of each 21-day cycle for at least 4 and no more than 6 cycles.

Drug: FKB238 (bevacizumab)
Drug: Paclitaxel
Drug: Carboplatin
Active Comparator: Avastin / paclitaxel / carboplatin

Drug: Avastin:

15 mg/kg IV infusion on Day 1 of each 21-day cycle.

Drug: Paclitaxel:

200 mg/m2 IV infusion on Day 1 of each 21-day cycle for at least 4 and no more than 6 cycles.

Drug: Carboplatin:

AUC = 6.0 IV infusion on Day 1 of each 21-day cycle for at least 4 and no more than 6 cycles.

Drug: Avastin (bevacizumab)
Drug: Paclitaxel
Drug: Carboplatin



Primary Outcome Measures :
  1. Overall Response Rate (ORR) Assessed as the Proportion of Patients With a Best Overall Response (BOR) of Either Complete Response (CR) or Partial Response (PR) [ Time Frame: Until data cut-off, which occurred 12 months after randomization of the last patient enrolled, for a total estimated period of time of up to approximately 30 months. ]
    The primary variable in this study was ORR, defined as the proportion of patients with a BOR of CR or PR (by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)). A BOR was defined as the best response (in the order of CR, PR, stable disease (SD), no evidence of disease (NED), progressive disease (PD), and not evaluable (NE)) among all post-baseline disease assessments that occurred until progression, or last evaluable assessment in the absence of progression prior to the initiation of subsequent anti-cancer therapy, irrespective of whether or not patients discontinued the study treatment. The 95% Pearson-Clopper confidence interval (CI) of ORR for each treatment arm was provided. Per RECIST v1.1 for target lesions and assessed by computed tomography (CT) or, if contraindicated, magnetic resonance imaging (MRI): CR=disappearance of all target lesions; PR=at least 30% decrease from baseline in the sum of diameters of target lesions. Overall Response=CR+PR.


Secondary Outcome Measures :
  1. ORR at Week 19 [ Time Frame: From the date of randomization up to Week 19. ]
    ORR (by RECIST v1.1) at Week 19 was defined as the proportion of patients with a BOR of CR or PR assessed at Week 19. Only tumor assessments performed up until 19 weeks (i.e. Week 18 assessment + 7 day assessment window) from randomization were considered in this analysis. Per RECIST v1.1 for target lesions and assessed by CT or, if contraindicated, MRI: CR=disappearance of all target lesions; PR=at least 30% decrease from baseline in the sum of diameters of target lesions. Overall Response=CR+PR.

  2. Progression-free Survival (PFS) [ Time Frame: Until data cut-off, which occurred 12 months after randomization of the last patient enrolled, for a total estimated period of time of up to approximately 30 months. ]
    The event of interest for PFS was defined as the interval from the date of randomization until first documented disease progression or death from any cause, whichever occurs first. Disease progression was based on tumor assessments according to RECIST v1.1 criteria. The items of the overall response CR, PR, SD and NED were taken as progression-free whereas PD denoted disease progression. PFS was summarized using Kaplan-Meier estimates of the quartiles for each treatment arm, and 95% CIs for the medians were calculated. Per RECIST v1.1 for target lesions and assessed by CT or, if contraindicated, MRI: PD=at least a 20% increase in the sum of the longest diameter of target lesions, unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions.

  3. Overall Survival (OS) [ Time Frame: Until data cut-off, which occurred 12 months after randomization of the last patient enrolled, for a total estimated period of time of up to approximately 30 months. ]
    The event of interest was defined as death from any cause. OS was defined as the interval from date of randomization until the date of death due to any cause. OS was summarized using Kaplan-Meier estimates of the quartiles for each treatment arm, and 95% CIs for the medians were calculated.

  4. Duration Of Response (DOR) [ Time Frame: Until data cut-off, which occurred 12 months after randomization of the last patient enrolled, for a total estimated period of time of up to approximately 30 months. ]
    DOR was evaluated in this study as a secondary efficacy endpoint. Only the patients defined as responders in the primary analysis of ORR were taken into account for the analysis of DOR. The event of interest was defined as first documented disease progression or death due to any reason, whichever occurred first. DOR was defined as the interval from the first documented response (as defined per RECIST v1.1) until the earlier date of the first documented disease progression or death due to any reason. The date of first documented response was taken as the date of the first tumor assessment with an overall visit response of CR or PR. Per RECIST v1.1 for target lesions and assessed by CT or, if contraindicated, MRI: CR=disappearance of all target lesions; PR=at least 30% decrease from baseline in the sum of diameters of target lesions. DOR was calculated in units of months.

  5. Disease Control Rate (DCR) Assessed as the Proportion of Patients With a BOR of Either CR, PR, SD or NED [ Time Frame: Until data cut-off, which occurred 12 months after randomization of the last patient enrolled, for a total estimated period of time of up to approximately 30 months. ]
    The DCR was defined as the proportion of patients defined as responders. The number and percentage of responders and non-responders and the 95% Pearson-Clopper CI of DCR for each treatment arm was provided. The odds ratio for treatment (FKB238 arm versus Avastin arm) and the corresponding 95% Wald CI were produced based on a logistic regression analysis of DCR. Per RECIST v1.1 for target lesions and assessed by CT or, if contraindicated, MRI: CR=disappearance of all target lesions; PR=at least 30% decrease from baseline in the sum of diameters of target lesions; SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. DCR=CR+PR+SD (≥ 6 weeks).


Other Outcome Measures:
  1. Serum Trough Concentration (Ctrough) [ Time Frame: Cycle 1 Day 1 (pre- and post-infusion), Cycle 2 Day 1 (pre), Cycle 4 Day 1 (pre and post), Cycle 6 Day 1 (pre), discontinuation visit, and every 12 weeks (up to 1 year [±14 days] after randomisation) until death, or the patient was lost to follow-up. ]
    Ctrough (pre-infusion) and serum maximum concentration (Cmax; at completion of infusion) were compared between treatment arms and time points, and descriptive statistics provided. Ctrough and Cmax concentrations were summarized using the pharmacokinetics (PK) population for each visit at which samples were taken. The pre-dose serum concentrations at Cycles 2, 4, and 6 were considered as Ctrough values and the post-dose serum concentrations at Cycles 1 and 4 were considered as Cmax values. PK data at Cycle 1 Day 1 pre-infusion were not calculable and are therefore not presented in the outcome measure data table. Data are only provided for the time points at which the serum trough concentration was measured.

  2. Proportion of Patients Developing Anti-drug Antibodies (ADAs) [ Time Frame: Pre-dose at Cycles 1, 2, 4 and 6, discontinuation visit, and every 12 weeks (up to 1 year [±14 days] after randomisation) until death, or the patient was lost to follow-up, whichever occurred first. ]
    The ADA levels were summarized at baseline and post-baseline time points using descriptive statistics.

  3. Adverse Events (AEs) [ Time Frame: From the time of signature of informed consent, throughout the treatment period and up to and including the 30-days after the last dose of study treatment, for a total estimated period of time of up to approximately 30 months. ]
  4. Vital Signs [ Time Frame: Up to approximately 30 days after last dose of study treatment. ]
  5. Hematology [ Time Frame: Up to approximately 30 days after last dose of study treatment. ]
  6. Clinical Chemistry [ Time Frame: Up to approximately 30 days after last dose of study treatment. ]
  7. Urinalysis [ Time Frame: Up to approximately 30 days after last dose of study treatment. ]
  8. Electrocardiogram [ Time Frame: Up to approximately 30 days after last dose of study treatment. ]
  9. Eastern Collaborative Oncology Group Performance Status [ Time Frame: Up to approximately 30 days after last dose of study treatment. ]
  10. Physical Examination [ Time Frame: Up to approximately 30 days after last dose of study treatment. ]


Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients aged 18 years or older
  • Newly diagnosed advanced (stage IV) /recurrent non-squamous NSCLC for which they had not received any systemic anti-cancer therapy for metastatic disease
  • Histologically or cytologically confirmed diagnosis of predominantly non-squamous NSCLC
  • Existence of at least 1 measurable lesion by RECIST v1.1
  • Adequate hematological, renal and liver function
  • Eastern Collaborative Oncology Group Performance Status (ECOG PS) 0 or 1
  • Life expectancy longer than 6 months

Exclusion Criteria:

  • Small cell lung cancer (SCLC) or combination SCLC and NSCLC. Squamous-cell tumors and mixed adenosquamous carcinomas of predominantly squamous nature
  • Any unresolved toxicities from prior systemic therapy
  • Known sensitizing epidermal growth factor receptor (EGFR) mutations or echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation positive mutations
  • Previous dosing with vascular endothelial growth factor (VEGF) inhibitor
  • Known hypersensitivity to any excipients of the Investigational Products (IPs) and combination chemotherapy
  • Use of prohibited concomitant medication
  • Known Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV) infection
  • Fertile men or women of childbearing potential not using adequate contraception.

Other inclusion/exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02810457


Locations
Show Show 147 study locations
Sponsors and Collaborators
Centus Biotherapeutics Limited
Investigators
Layout table for investigator information
Study Director: Centus Biotherapeutics Limited Centus Biotherapeutics Limited
  Study Documents (Full-Text)

Documents provided by Centus Biotherapeutics Limited:
Study Protocol  [PDF] May 22, 2018
Statistical Analysis Plan  [PDF] May 7, 2019

Layout table for additonal information
Responsible Party: Centus Biotherapeutics Limited
ClinicalTrials.gov Identifier: NCT02810457    
Other Study ID Numbers: FKB238-002
2015-004104-33 ( EudraCT Number )
First Posted: June 23, 2016    Key Record Dates
Results First Posted: March 19, 2020
Last Update Posted: March 19, 2020
Last Verified: March 2020
Keywords provided by Centus Biotherapeutics Limited:
Cancer
Bevacizumab
Carboplatin
Paclitaxel
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Paclitaxel
Bevacizumab
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors