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Safety and Efficacy Study of Avastin in Locally Advanced Metastatic or Recurrent Non-small Lung Cancer (NSLC) Participants

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ClinicalTrials.gov Identifier: NCT02596958
Recruitment Status : Completed
First Posted : November 4, 2015
Results First Posted : March 4, 2016
Last Update Posted : April 4, 2016
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Observational
Study Design Observational Model: Case Control;   Time Perspective: Cross-Sectional
Condition Non-Squamous Non-Small Cell Lung Cancer
Intervention Drug: Bevacizumab
Enrollment 996

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Bevacizumab
Hide Arm/Group Description Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current summary of product characteristics (SmPC).
Period Title: Overall Study
Started 996
Completed 0
Not Completed 996
Reason Not Completed
Serious Adverse Drug Reactions             44
Cancer Progression             441
Death From Cancer             112
Death From Other Cause             33
Refusal of Treatment/Poor Cooperation             61
Administrative Reasons/Other             231
Lost to Follow-up             33
Missing             32
Excluded Due to Second Line Treatment             9
Arm/Group Title Bevacizumab
Hide Arm/Group Description Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Overall Number of Baseline Participants 987
Hide Baseline Analysis Population Description
Analysis population was defined as all participants included in the observational study, regardless of whether they finished it or not. Nine hundred and ninety six (996) participants were documented but only 987 participants were included in the analysis population as 9 participants were excluded due to documented second line treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 987 participants
61.5  (9.8)
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 987 participants
Female 396
Male 590
Missing 1
1.Primary Outcome
Title Percentage of Participants With Adverse Drug Reactions (ADRs), Toxicities, Avastin-Related ADRs, and Serious ADRs
Hide Description ADRs were defined as any response to a drug which was noxious and unintended, and which occurred at dose normally used related to the pharmacological properties. Serious ADRs were defined as any untoward medical occurrence or effect that at any dose resulted in death or life-threatening conditions or required hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, congenital anomaly or birth defect or medically important condition. Toxicity was defined as an adverse event that had an attribution (the relationship to investigational agent) of possible, probable or definite. Avastin-related ADRs (an adverse event with a possible relationship or a relationship to the treatment with AVASTIN) were due to Avastin. ADRs includes serious as well as non-serious ADRs.
Time Frame Up to 74 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis population was defined as all participants included in the observational study, regardless of whether they finished it or not.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Overall Number of Participants Analyzed 987
Measure Type: Number
Unit of Measure: percentage of participants
ADRs 88.6
Toxicities 88.2
Avastin-related ADR 27.0
Serious ADR 11.1
2.Secondary Outcome
Title Percentage of Participants Who Withdrew or Modified Treatment
Hide Description Percentage of participants who withdrew treatment or experienced at least 1 dose deviation in relation to the planned Avastin therapy were reported.
Time Frame Up to 74 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis population was defined as all participants included in the observational study, regardless of whether they finished it.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Overall Number of Participants Analyzed 987
Measure Type: Number
Unit of Measure: percentage of participants
8.8
3.Secondary Outcome
Title Number of Cycles of Systemic Therapy
Hide Description Number of cycles of systemic therapy was the mean number of cycles received by participants in combination therapy with Avastin and chemotherapy and with Avastin monotherapy (maintenance).
Time Frame Up to 74 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis population was defined as all participants included in the observational study, regardless of whether they finished it.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Overall Number of Participants Analyzed 987
Mean (Standard Deviation)
Unit of Measure: cycles
Total number of cycles 7.6  (7.0)
Number of cycles with combination therapy 4.2  (1.8)
Number of cycles with maintenance therapy 3.4  (6.2)
4.Secondary Outcome
Title Percentage of Participants With Best Tumor Response Over Time
Hide Description Best tumor response (assessed as per clinical routine of the individual center) was categorized according to the following criteria at the investigator discretion: complete response (CR: commonly defined as disappearance of all target lesions, all non-target lesions, and no new lesion), partial response (PR: commonly defined as at least a 30 percent [%] decrease in the sum of the longest diameter [LD] of target lesions, no progression in non-target lesion, and no new lesion), stable disease (SD: commonly defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD], in addition to no new target lesions). PD: commonly defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started and not evaluable (NE).
Time Frame Up to 74 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis population was defined as all participants included in the observational study, regardless of whether they finished it. Here, number of participants analyzed = participants with non-missing tumor response data.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Overall Number of Participants Analyzed 976
Measure Type: Number
Unit of Measure: percentage of participants
CR 2.3
PR 43.3
SD 29.4
PD 10.1
NE 14.9
5.Secondary Outcome
Title Percentage of Participants With Eastern Cooperative Group(ECOG) Performance Status Grades
Hide Description ECOG Performance Status measured on-therapy (time between first dose and last dose date with a 30-day lag) assessed participant's performance status on 5 point scale: 0 is equal to (=) fully active/able to carry on all pre-disease activities without restriction; 1=restricted in physically strenuous activity, ambulatory/able to carry out light or sedentary work; 2=ambulatory (greater than [>] 50% of waking hours [hrs]), capable of all self care, unable to carry out any work activities; 3=capable of only limited self care, confined to bed/chair >50% of waking hrs; 4=completely disabled, cannot carry on any self care, totally confined to bed/chair; 5=dead.
Time Frame Up to 74 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis population was defined as all participants included in the observational study, regardless of whether they finished it. Here, number of participants analyzed = participants with non-missing tumor response data.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Overall Number of Participants Analyzed 806
Measure Type: Number
Unit of Measure: percentage of participants
Grade 0 18.7
Grade 1 50.1
Grade 2 23.2
Grade 3 6.2
Grade 4 1.7
6.Secondary Outcome
Title Percentage of Participants With Disease Control
Hide Description Disease control was defined as having achieved CR (commonly defined as disappearance of all target lesions, all non-target lesions, and no new lesion), PR (commonly defined as at least a 30% decrease in the sum of the LD of target lesions, no progression in non-target lesion, and no new lesion), or SD (commonly defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, in addition to no new target lesions) during the course of observation which were assessed as per investigator discretion. PD: commonly defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started and NE.
Time Frame Up to 74 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis population was defined as all participants included in the observational study, regardless of whether they finished it. Here, number of participants analyzed = participants with non-missing tumor response data.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Overall Number of Participants Analyzed 976
Measure Type: Number
Unit of Measure: percentage of participants
75.0
7.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS was defined as the time (months) between the start of therapy and progression (unequivocal progression of existing non­target lesions) or death. Progression: at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started. PFS was estimated using Kaplan-Meier method.
Time Frame Up to 74 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis population was defined as all participants included in the observational study, regardless of whether they finished it. Here, number of participants analyzed = participants with non-missing tumor response data.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Overall Number of Participants Analyzed 941
Median (95% Confidence Interval)
Unit of Measure: months
7.4
(7.1 to 8.4)
8.Secondary Outcome
Title Percentage of Participants Who Died
Hide Description [Not Specified]
Time Frame Up to 74 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis population was defined as all participants included in the observational study, regardless of whether they finished it. Here, number of participants analyzed = participants with non-missing tumor response data.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Overall Number of Participants Analyzed 975
Measure Type: Number
Unit of Measure: percentage of participants
17.5
9.Secondary Outcome
Title Overall Survival
Hide Description Overall survival was defined as the time (months) between the start of therapy and the date of death.
Time Frame Up to 74 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Analysis population was defined as all participants included in the observational study, regardless of whether they finished it. Here 'number of participants analyzed' = participants assessed for this outcome measure.
Arm/Group Title Bevacizumab
Hide Arm/Group Description:
Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
Overall Number of Participants Analyzed 975
Mean (Standard Deviation)
Unit of Measure: months
18.4  (0.5)
Time Frame Up to the end of study (median duration of 170.8 days)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Bevacizumab
Hide Arm/Group Description Participants received bevacizumab (Avastin) in addition to platinum based chemotherapy for up to 6 cycles (21-day cycles) followed by bevacizumab as a single agent until disease progression. The dose and administration schedule was at the discretion of the treating physician and as per the recommendations given in the current SmPC.
All-Cause Mortality
Bevacizumab
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Bevacizumab
Affected / at Risk (%)
Total   110/987 (11.14%) 
Blood and lymphatic system disorders   
Leukopenia * 1  5/987 (0.51%) 
Anaemia * 1  4/987 (0.41%) 
Febrile neutropenia * 1  2/987 (0.20%) 
Neutropenia * 1  2/987 (0.20%) 
Pancytopenia * 1  2/987 (0.20%) 
Thrombocytopenia * 1  2/987 (0.20%) 
Splenic infarction * 1  1/987 (0.10%) 
Cardiac disorders   
Cardiac failure * 1  4/987 (0.41%) 
Gastrointestinal disorders   
Large intestine perforation * 1  4/987 (0.41%) 
Nausea * 1  3/987 (0.30%) 
Gastrointestinal haemorrhage * 1  1/987 (0.10%) 
Gastrointestinal perforation * 1  1/987 (0.10%) 
Large intestinal haemorrhage * 1  1/987 (0.10%) 
Rectal haemorrhage * 1  1/987 (0.10%) 
Vomiting * 1  1/987 (0.10%) 
General disorders   
Death * 1  4/987 (0.41%) 
Infections and infestations   
Pneumonia * 1  9/987 (0.91%) 
Sepsis * 1  4/987 (0.41%) 
Peritonitis * 1  3/987 (0.30%) 
Musculoskeletal and connective tissue disorders   
Fistula * 1  2/987 (0.20%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Malignant neoplasm progression * 1  4/987 (0.41%) 
Metastases to central nervous system * 1  2/987 (0.20%) 
Nervous system disorders   
Cerebral haemorrhage * 1  3/987 (0.30%) 
Cerebral ischaemia * 1  1/987 (0.10%) 
Renal and urinary disorders   
Proteinuria * 1  3/987 (0.30%) 
Respiratory, thoracic and mediastinal disorders   
Pulmonary embolism * 1  15/987 (1.52%) 
Haemoptysis * 1  7/987 (0.71%) 
Dyspnoea * 1  5/987 (0.51%) 
Acquired tracheo-oesophageal fistula * 1  1/987 (0.10%) 
Bronchial haemorrhage * 1  1/987 (0.10%) 
Oesophagobronchial fistula * 1  1/987 (0.10%) 
Pleural fistula * 1  1/987 (0.10%) 
Pulmonary haemorrhage * 1  1/987 (0.10%) 
Vascular disorders   
Hypertension * 1  15/987 (1.52%) 
Haemorrhage * 1  1/987 (0.10%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (15.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bevacizumab
Affected / at Risk (%)
Total   851/987 (86.22%) 
Blood and lymphatic system disorders   
Anaemia * 1  594/987 (60.18%) 
Leukopenia * 1  492/987 (49.85%) 
Neutropenia * 1  311/987 (31.51%) 
Thrombocytopenia * 1  307/987 (31.10%) 
Gastrointestinal disorders   
Nausea * 1  459/987 (46.50%) 
Vomiting * 1  185/987 (18.74%) 
Diarrhoea * 1  99/987 (10.03%) 
General disorders   
Pain * 1  171/987 (17.33%) 
Pyrexia * 1  102/987 (10.33%) 
Chest pain * 1  66/987 (6.69%) 
Musculoskeletal and connective tissue disorders   
Pain in extremity * 1  68/987 (6.89%) 
Back pain * 1  50/987 (5.07%) 
Nervous system disorders   
Peripheral sensory neuropathy * 1  111/987 (11.25%) 
Renal and urinary disorders   
Proteinuria * 1  56/987 (5.67%) 
Respiratory, thoracic and mediastinal disorders   
Epistaxis * 1  61/987 (6.18%) 
Skin and subcutaneous tissue disorders   
Palmar-plantar erythrodysaesthesia syndrome * 1  99/987 (10.03%) 
Vascular disorders   
Hypertension * 1  134/987 (13.58%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (15.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Hoffmann-LaRoche
Phone: 800-821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02596958     History of Changes
Other Study ID Numbers: ML21217
First Submitted: November 3, 2015
First Posted: November 4, 2015
Results First Submitted: February 5, 2016
Results First Posted: March 4, 2016
Last Update Posted: April 4, 2016