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A Study of First Line Treatment With Avastin (Bevacizumab) in Combination With Carboplatin and Weekly Paclitaxel in Patients With Ovarian Cancer

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ClinicalTrials.gov Identifier: NCT00937560
Recruitment Status : Completed
First Posted : July 13, 2009
Results First Posted : February 24, 2015
Last Update Posted : November 6, 2017
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Ovarian Cancer
Interventions Drug: Bevacizumab
Drug: Paclitaxel
Drug: Carboplatin
Enrollment 190
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Bevacizumab + Paclitaxel + Carboplatin
Hide Arm/Group Description Participants received 6-8 (at the investigator’s discretion) 3-week cycles of bevacizumab 7.5 milligrams per kilograms (mg/kg) intravenously (IV) on Day 1 of each cycle, paclitaxel 80 milligrams per square meters of body surface (mg/m^2) IV on Days 1, 8, and 15 of each cycle, and carboplatin IV to an area under the curve (AUC) of 6 on Day 1 of each cycle. The initial dose of carboplatin was calculated according to the Calvert formula (milligrams [mg] equals [=] [glomerular filtration rate (GFR) + 25] x 6). Following the initial treatment (bevacizumab + paclitaxel + carboplatin) period, participants received additional 3-week cycles of monotherapy bevacizumab 7.5 mg/kg IV during the maintenance treatment period. The total maximum bevacizumab treatment duration was 17 cycles, (12 months) which included both the initial treatment period and the bevacizumab monotherapy maintenance treatment period.
Period Title: Initial Treatment
Started 189
Received Treatment 189
Completed 168
Not Completed 21
Reason Not Completed
Death             6
Withdraw consent             3
Adverse Event             1
Lost to Follow-up             1
No end of study page             10
Period Title: Maintenance Treatment
Started 168
Completed 150
Not Completed 18
Reason Not Completed
Death             12
Withdraw consent             5
According to protocol             1
Arm/Group Title Bevacizumab + Paclitaxel + Carboplatin
Hide Arm/Group Description Participants received 6-8 (at the investigator’s discretion) 3-week cycles of bevacizumab 7.5 mg/kg IV on Day 1 of each cycle, paclitaxel 80 mg/m^2 IV on Days 1, 8, and 15 of each cycle, and carboplatin IV to an AUC of 6 on Day 1 of each cycle. The initial dose of carboplatin was calculated according to the Calvert formula (mg = [GFR + 25] x 6). Following the initial treatment (bevacizumab + paclitaxel + carboplatin) period, participants received additional 3-week cycles of monotherapy bevacizumab 7.5 mg/kg IV during the maintenance treatment period. The total maximum bevacizumab treatment duration was 17 cycles, (12 months) which included both the initial treatment period and the bevacizumab monotherapy maintenance treatment period.
Overall Number of Baseline Participants 189
Hide Baseline Analysis Population Description
Intent-to-treat population: All enrolled participants who received at least 1 dose of any study medication (bevacizumab, carboplatin or paclitaxel).
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 189 participants
55
(24 to 79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 189 participants
Female
189
 100.0%
Male
0
   0.0%
1.Primary Outcome
Title Progression-free Survival
Hide Description Progression-free survival was defined as the time from the first administration of any study treatment to the first disease progression using Response Evaluation Criteria In Solid Tumors (RECIST) or death from any cause, whichever occurred first.
Time Frame Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All enrolled participants who received at least 1 dose of any study medication (bevacizumab, carboplatin, or paclitaxel).
Arm/Group Title Bevacizumab + Paclitaxel + Carboplatin
Hide Arm/Group Description:
Participants received 6-8 (at the investigator’s discretion) 3-week cycles of bevacizumab 7.5 mg/kg IV on Day 1 of each cycle, paclitaxel 80 mg/m^2 IV on Days 1, 8, and 15 of each cycle, and carboplatin IV to an AUC of 6 on Day 1 of each cycle. The initial dose of carboplatin was calculated according to the Calvert formula (mg = [GFR + 25] x 6). Following the initial treatment (bevacizumab + paclitaxel + carboplatin) period, participants received additional 3-week cycles of monotherapy bevacizumab 7.5 mg/kg IV during the maintenance treatment period. The total maximum bevacizumab treatment duration was 17 cycles, (12 months) which included both the initial treatment period and the bevacizumab monotherapy maintenance treatment period.
Overall Number of Participants Analyzed 189
Median (90% Confidence Interval)
Unit of Measure: Months
23.7
(19.9 to 26.4)
2.Secondary Outcome
Title Percentage of Participants With an Objective Response
Hide Description An objective response was defined as either a complete response (CR) or a partial response (PR). Using the Response Evaluation Criteria in Solid Tumors (RECIST), a CR was defined as the disappearance of all target lesions and all non-target lesions, normalization of tumor marker level, and no new lesions and a PR was defined as the disappearance of all target lesions and persistence of ≥ 1 non-target lesions and/or the maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diameter of target lesions, and no new lesions or unequivocal progression of existing non-target lesions. Only participants with measurable disease were included in the analysis according to RECIST only. Only participants with a Baseline ovarian cancer mucin CA-125 level ≥ 2 times the upper limit of normal who had a ≥ 50% reduction of CA-125 from Baseline were included in the analysis according to CA-125 level.
Time Frame Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All enrolled participants who received at least 1 dose of any study medication (bevacizumab, carboplatin, or paclitaxel).
Arm/Group Title Bevacizumab + Paclitaxel + Carboplatin
Hide Arm/Group Description:
Participants received 6-8 (at the investigator’s discretion) 3-week cycles of bevacizumab 7.5 mg/kg IV on Day 1 of each cycle, paclitaxel 80 mg/m^2 IV on Days 1, 8, and 15 of each cycle, and carboplatin IV to an AUC of 6 on Day 1 of each cycle. The initial dose of carboplatin was calculated according to the Calvert formula (mg = [GFR + 25] x 6). Following the initial treatment (bevacizumab + paclitaxel + carboplatin) period, participants received additional 3-week cycles of monotherapy bevacizumab 7.5 mg/kg IV during the maintenance treatment period. The total maximum bevacizumab treatment duration was 17 cycles, (12 months) which included both the initial treatment period and the bevacizumab monotherapy maintenance treatment period.
Overall Number of Participants Analyzed 126
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
RECIST only (N=91)
84.6
(75.5 to 91.3)
CA-125 level only (N=101)
97.0
(91.6 to 99.4)
RECIST and CA-125 level combined (N=126)
92.1
(85.9 to 96.1)
3.Secondary Outcome
Title Duration of Response
Hide Description Duration of response was defined as the interval between the date of the first documented response by RECIST to the date of first disease progression or death, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Only participants with measurable disease were included in the analysis according to RECIST only. Only participants with a Baseline ovarian cancer mucin CA-125 level ≥ 2 times the upper limit of normal who had a ≥ 50% reduction of CA-125 from Baseline were included in the analysis according to CA-125 level.
Time Frame Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All enrolled participants who received at least 1 dose of any study medication (bevacizumab, carboplatin, or paclitaxel).
Arm/Group Title Bevacizumab + Paclitaxel + Carboplatin
Hide Arm/Group Description:
Participants received 6-8 (at the investigator’s discretion) 3-week cycles of bevacizumab 7.5 mg/kg IV on Day 1 of each cycle, paclitaxel 80 mg/m^2 IV on Days 1, 8, and 15 of each cycle, and carboplatin IV to an AUC of 6 on Day 1 of each cycle. The initial dose of carboplatin was calculated according to the Calvert formula (mg = [GFR + 25] x 6). Following the initial treatment (bevacizumab + paclitaxel + carboplatin) period, participants received additional 3-week cycles of monotherapy bevacizumab 7.5 mg/kg IV during the maintenance treatment period. The total maximum bevacizumab treatment duration was 17 cycles, (12 months) which included both the initial treatment period and the bevacizumab monotherapy maintenance treatment period.
Overall Number of Participants Analyzed 116
Median (95% Confidence Interval)
Unit of Measure: Months
RECIST only (N=77)
14.7
(12.7 to 16.1)
CA-125 level only (N=98)
17.5
(15.4 to 21.9)
RECIST and CA-125 level combined (N=116)
17.4
(15.4 to 21.9)
4.Secondary Outcome
Title Overall Survival at 1 Year and 2 Years
Hide Description Reported are the percentage of participants that were alive at 1 year and 2 years after enrolling in the study.
Time Frame Baseline to Year 2
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All enrolled participants who received at least 1 dose of any study medication (bevacizumab, carboplatin, or paclitaxel).
Arm/Group Title Bevacizumab + Paclitaxel + Carboplatin
Hide Arm/Group Description:
Participants received 6-8 (at the investigator’s discretion) 3-week cycles of bevacizumab 7.5 mg/kg IV on Day 1 of each cycle, paclitaxel 80 mg/m^2 IV on Days 1, 8, and 15 of each cycle, and carboplatin IV to an AUC of 6 on Day 1 of each cycle. The initial dose of carboplatin was calculated according to the Calvert formula (mg = [GFR + 25] x 6). Following the initial treatment (bevacizumab + paclitaxel + carboplatin) period, participants received additional 3-week cycles of monotherapy bevacizumab 7.5 mg/kg IV during the maintenance treatment period. The total maximum bevacizumab treatment duration was 17 cycles, (12 months) which included both the initial treatment period and the bevacizumab monotherapy maintenance treatment period.
Overall Number of Participants Analyzed 189
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
Year 1
97.7
(95.4 to 99.9)
Year 2
92.1
(88.0 to 96.2)
5.Secondary Outcome
Title Biological Progression-free Interval
Hide Description Biological progression-free interval is defined as the interval from the date of the first administration of any study treatment to the date of the first documented serial elevation of the ovarian cancer mucin CA-125. More precisely, this is defined as the first documented increase in CA-125 levels as follows: (1) CA-125 greater than or equal to 2 times the upper level of normal (ULN) on 2 occasions at least 1 week apart (for patients with CA-125 within normal range pre-treatment) or (2) CA-125 greater than or equal to 2 times the ULN on 2 occasions at least 1 week apart (for patients with elevated CA-125 pre-treatment and initial normalisation of CA-125 on-treatment) or (3) CA-125 greater than or equal to 2 times the nadir value, which is the lowest observed CA-125 value per patient on 2 occasions at least 1 week apart (for patients with elevated CA-125 pre-treatment which never normalised).
Time Frame Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All enrolled participants who received at least 1 dose of any study medication (bevacizumab, carboplatin, or paclitaxel).
Arm/Group Title Bevacizumab + Paclitaxel + Carboplatin
Hide Arm/Group Description:
Participants received 6-8 (at the investigator’s discretion) 3-week cycles of bevacizumab 7.5 mg/kg IV on Day 1 of each cycle, paclitaxel 80 mg/m^2 IV on Days 1, 8, and 15 of each cycle, and carboplatin IV to an AUC of 6 on Day 1 of each cycle. The initial dose of carboplatin was calculated according to the Calvert formula (mg = [GFR + 25] x 6). Following the initial treatment (bevacizumab + paclitaxel + carboplatin) period, participants received additional 3-week cycles of monotherapy bevacizumab 7.5 mg/kg IV during the maintenance treatment period. The total maximum bevacizumab treatment duration was 17 cycles, (12 months) which included both the initial treatment period and the bevacizumab monotherapy maintenance treatment period.
Overall Number of Participants Analyzed 189
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(NA to NA)
[1]
The median and the limits of the 95% confidence interval could not be calculated due to too few events.
Time Frame Baseline to the end of the study (up to 4 years, 1 month)
Adverse Event Reporting Description Safety population: All enrolled participants who received at least 1 dose of any study medication (bevacizumab, carboplatin, or paclitaxel).
 
Arm/Group Title Bevacizumab + Paclitaxel + Carboplatin
Hide Arm/Group Description Participants received 6-8 (at the investigator’s discretion) 3-week cycles of bevacizumab 7.5 mg/kg intravenously (iv) on Day 1 of each cycle, paclitaxel 80 mg/m^2 iv on Days 1, 8, and 15 of each cycle, and carboplatin iv to an area under the curve of 6 on Day 1 of each cycle. The initial dose of carboplatin was calculated according to the Calvert formula (mg = [glomerular filtration rate + 25] x 6). Following the combination treatments, participants received up to 17 3-week cycles of bevacizumab 7.5 mg/g iv alone. Bevacizumab: Bevacizumab was supplied as a sterile solution for infusion. Paclitaxel: Paclitaxel was supplied locally in commercial batches. Carboplatin: Carboplatin was supplied locally in commercial batches.
All-Cause Mortality
Bevacizumab + Paclitaxel + Carboplatin
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Bevacizumab + Paclitaxel + Carboplatin
Affected / at Risk (%)
Total   43/189 (22.75%) 
Blood and lymphatic system disorders   
Neutropenia * 1  5/189 (2.65%) 
Anaemia * 1  2/189 (1.06%) 
Thrombocytopenia * 1  1/189 (0.53%) 
Cardiac disorders   
Atrial fibrillation  1  1/189 (0.53%) 
Tachycardia * 1  1/189 (0.53%) 
Ear and labyrinth disorders   
Deafness * 1  1/189 (0.53%) 
Gastrointestinal disorders   
Subileus  1  3/189 (1.59%) 
Gastrointestinal obstruction * 1  2/189 (1.06%) 
Gastrointestinal perforation * 1  1/189 (0.53%) 
Oesophagits * 1  1/189 (0.53%) 
Abdominal pain * 1  1/189 (0.53%) 
Abdominal pain upper * 1  1/189 (0.53%) 
Diarrhoea * 1  1/189 (0.53%) 
Ileus * 1  1/189 (0.53%) 
Intestinal obstruction * 1  1/189 (0.53%) 
General disorders   
Pyrexia * 1  2/189 (1.06%) 
Chest discomfort * 1  1/189 (0.53%) 
Immune system disorders   
Hypersensitivity * 1  1/189 (0.53%) 
Infections and infestations   
Urinary tract infection  1  2/189 (1.06%) 
Appendicitis * 1  1/189 (0.53%) 
Bacteraemia * 1  1/189 (0.53%) 
Bacterial sepsis * 1  1/189 (0.53%) 
Catheter site infection * 1  1/189 (0.53%) 
Cellulitis * 1  1/189 (0.53%) 
Device related infection * 1  1/189 (0.53%) 
Infected lymphocele * 1  1/189 (0.53%) 
Pneumonia * 1  1/189 (0.53%) 
Urosepsis * 1  1/189 (0.53%) 
Injury, poisoning and procedural complications   
Postoperative adhesion * 1  1/189 (0.53%) 
Musculoskeletal and connective tissue disorders   
Pain in extremity * 1  1/189 (0.53%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
B-cell lymphoma  1  1/189 (0.53%) 
Colorectal cancer * 1  1/189 (0.53%) 
Second primary malignancy * 1  1/189 (0.53%) 
Nervous system disorders   
Cerebral infarction  1  1/189 (0.53%) 
Cerebral ischaemia * 1  1/189 (0.53%) 
Intracranial aneurysm * 1  1/189 (0.53%) 
Subarachnoid haemorrhage * 1  1/189 (0.53%) 
Syncope * 1  1/189 (0.53%) 
Renal and urinary disorders   
Haematuria * 1  1/189 (0.53%) 
Respiratory, thoracic and mediastinal disorders   
Pulmonary embolism * 1  2/189 (1.06%) 
Epistaxis * 1  1/189 (0.53%) 
Pneumonitis * 1  1/189 (0.53%) 
Pneumothorax * 1  1/189 (0.53%) 
Vascular disorders   
Deep vein thrombosis * 1  1/189 (0.53%) 
Embolism venous * 1  1/189 (0.53%) 
Hypertension * 1  1/189 (0.53%) 
Hypertensive crisis * 1  1/189 (0.53%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (15.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Bevacizumab + Paclitaxel + Carboplatin
Affected / at Risk (%)
Total   186/189 (98.41%) 
Blood and lymphatic system disorders   
Neutropenia  1  153/189 (80.95%) 
Thrombocytopenia * 1  85/189 (44.97%) 
Anaemia * 1  111/189 (58.73%) 
Leukopenia * 1  48/189 (25.40%) 
Lymphopenia * 1  14/189 (7.41%) 
Thrombocytosis  1  11/189 (5.82%) 
Gastrointestinal disorders   
Nausea * 1  87/189 (46.03%) 
Diarrhoea * 1  59/189 (31.22%) 
Constipation * 1  64/189 (33.86%) 
Stomatitis * 1  39/189 (20.63%) 
Vomiting * 1  43/189 (22.75%) 
Abdominal pain * 1  31/189 (16.40%) 
Abdominal pain upper * 1  20/189 (10.58%) 
Gingival bleeding * 1  13/189 (6.88%) 
General disorders   
Fatigue  1  105/189 (55.56%) 
Asthenia * 1  22/189 (11.64%) 
Pyrexia * 1  19/189 (10.05%) 
Mucosal inflammation * 1  15/189 (7.94%) 
Infections and infestations   
Urinary tract infection * 1  21/189 (11.11%) 
Upper respiratory tract infection * 1  18/189 (9.52%) 
Investigations   
Alanine aminotransferase increased * 1  19/189 (10.05%) 
Aspartate aminotransferase increased * 1  14/189 (7.41%) 
Metabolism and nutrition disorders   
Hyperglycaemia * 1  16/189 (8.47%) 
Decreased appetite * 1  19/189 (10.05%) 
Hypokalaemia * 1  16/189 (8.47%) 
Hypercholesterolaemia * 1  12/189 (6.35%) 
Hypoalbuminemia * 1  11/189 (5.82%) 
Musculoskeletal and connective tissue disorders   
Arthralgia * 1  42/189 (22.22%) 
Myalgia * 1  28/189 (14.81%) 
Musculoskeletal pain * 1  18/189 (9.52%) 
Back pain * 1  18/189 (9.52%) 
Pain in extremity * 1  11/189 (5.82%) 
Musculoskeletal chest pain * 1  10/189 (5.29%) 
Nervous system disorders   
Peripheral sensory neuropathy * 1  80/189 (42.33%) 
Headache * 1  34/189 (17.99%) 
Paraesthesia * 1  25/189 (13.23%) 
Dysgeusia * 1  22/189 (11.64%) 
Dizziness * 1  14/189 (7.41%) 
Psychiatric disorders   
Insomnia * 1  12/189 (6.35%) 
Renal and urinary disorders   
Proteinuria * 1  11/189 (5.82%) 
Respiratory, thoracic and mediastinal disorders   
Epistaxis  1  76/189 (40.21%) 
Dysphonia  1  10/189 (5.29%) 
Cough * 1  13/189 (6.88%) 
Nasopharyngitis * 1  17/189 (8.99%) 
Skin and subcutaneous tissue disorders   
Alopecia  1  89/189 (47.09%) 
Rash * 1  16/189 (8.47%) 
Nail disorder * 1  15/189 (7.94%) 
Erythema * 1  10/189 (5.29%) 
Nail toxicity * 1  11/189 (5.82%) 
Vascular disorders   
Hypertension * 1  44/189 (23.28%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (15.0)
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-La Roche
Phone: 800 821-8590
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00937560     History of Changes
Other Study ID Numbers: MO22225
2008-008336-85 ( EudraCT Number )
First Submitted: July 6, 2009
First Posted: July 13, 2009
Results First Submitted: February 9, 2015
Results First Posted: February 24, 2015
Last Update Posted: November 6, 2017