The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Trial of Vinflunine Versus Alkylating Agent in Metastatic Breast Cancer

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: NCT01091168
Recruitment Status : Completed
First Posted : March 23, 2010
Results First Posted : September 16, 2019
Last Update Posted : September 16, 2019
Sponsor:
Information provided by (Responsible Party):
Pierre Fabre Medicament

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Breast Cancer
Metastases
Interventions Drug: vinflunine
Drug: Alkylating agent of physician choice registered in cancer
Enrollment 594
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Vinflunine (VFL) Alkylating Agent
Hide Arm/Group Description

Patients randomised in the test arm (arm A) received Vinflunine at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks.

vinflunine: 280 mg/m2 on day 1 of each cycle every 3 weeks

Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country.

Alkylating agent of physician choice registered in cancer: cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin
Period Title: Overall Study
Started 298 296
Completed 0 0
Not Completed 298 296
Reason Not Completed
Progressive disease             250             234
Adverse Event             21             24
Lost to Follow-up             0             1
Physician, patient's decision, other             27             37
Arm/Group Title Arm A: Vinflunine Arm B: Alkylating Agent of Physician Choice Total
Hide Arm/Group Description

Patients randomised in the test arm (arm A) received VFL at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks.

vinflunine: 280 mg/m2 on day 1 of each cycle every 3 weeks

Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country.

Alkylating agent of physician choice registered in cancer: cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin

 Total of all reporting groups
Overall Number of Baseline Participants 298 296 594
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 298 participants 296 participants 594 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
236
  79.2%
227
  76.7%
463
  77.9%
>=65 years
62
  20.8%
69
  23.3%
131
  22.1%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 298 participants 296 participants 594 participants
Female
298
 100.0%
296
 100.0%
594
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Overall Survival
Hide Description The main endpoint of this study is overall survival defined as the time from randomisation to the date of death or last follow-up. For patients who have not died, survival duration will be censored at the date of last contact or last follow-up or the date of last news.
Time Frame From baseline up to 3 years 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Vinflunine Alkylating Agent
Hide Arm/Group Description:

Patients randomised in the test arm (arm A) received VFL at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks.

vinflunine: 280 mg/m2 on day 1 of each cycle every 3 weeks

Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country.

Alkylating agent of physician choice registered in cancer: cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin
Overall Number of Participants Analyzed 298 296
Median (95% Confidence Interval)
Unit of Measure: Months
9.1
(7.7 to 10.4)
9.3
(7.5 to 10.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vinflunine, Alkylating Agent
Comments Kaplan-Meier curves and life tables by treatment arm were provided. Confidence intervals on the median were calculated using the Brookmeyer and Crowley method. Hazard ratio and 95% confidence intervals were reported. A stratified Cox proportional model was performed to compare the two treatment arms taking into account the stratification factors (except centre) used at the time of randomisation.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.673
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.86 to 1.25
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description DCR was defined as the proportion of patients with Complete Response (CR), Partial Response (PR) and stable disease (SD), relative to the total number of patients in the analysed population.
Time Frame From baseline up to 3 years 1 month
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Vinflunine Alkylating Agent
Hide Arm/Group Description:

Patients randomised in the test arm (arm A) received VFL at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks.

vinflunine: 280 mg/m2 on day 1 of each cycle every 3 weeks

Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country.

Alkylating agent of physician choice registered in cancer: cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin
Overall Number of Participants Analyzed 298 296
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
43.6
(37.9 to 49.3)
35.5
(30 to 41.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vinflunine, Alkylating Agent
Comments The disease control rate (DCR) were compared in the ITT population and in the population evaluable for response between the 2 arms with a cochran Mantel Haenszel, stratified on WHO performance status at baseline, number of prior chemotherapy lines for the treatment of disease and disease measurability at Baseline.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0424
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
3.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description PFS was defined as the time from randomisation to the first tumour progression or death due to any cause in the absence of previous documentation of objective tumour progression. PFS was performed in the ITT and eligible populations every 6 weeks based on RECIST version 1.1. For patients lost of follow up, or without a known record of progression or death, PFS was censored at the date of last tumour assessment or the date of last contact of a follow-up showing no progression which ever occured last.
Time Frame From baseline to cut-off date(27 August 2012), up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Vinflunine Alkylating Agent
Hide Arm/Group Description:

Patients randomised in the test arm (arm A) received VFL at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks.

vinflunine: 280 mg/m2 on day 1 of each cycle every 3 weeks

Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country.

Alkylating agent of physician choice registered in cancer: cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin
Overall Number of Participants Analyzed 298 296
Median (95% Confidence Interval)
Unit of Measure: Months
2.5
(1.7 to 2.7)
1.9
(1.5 to 2.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vinflunine, Alkylating Agent
Comments PFS was compared between the 2 treatment arms by the log-rank test procedure with the 5 % significant level, stratified on the stratification factors (except study site) as specified at the time of randomisation. Os was analysed using Kaplan-Meir method and summarized with median and 95% CI of the median
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4927
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.8 to 1.12
Estimation Comments [Not Specified]
Time Frame Adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment (max treatment duration: 90 weeks) at the exception of Serious Adverse Events (SAE) occured after discontinuation and start of a further treatment, up to 4 years. AEs were collected from treated patients who received at least one study medication (N= 297 in vinflunine arm and N=290 in alkylating agent arm).
Adverse Event Reporting Description The same event may appear as both an AE and SAE. However what is presented are distinct events. An event may be categorized as serious in 1 subject and as non serious in another. Specific AE tables were generated separately as per Eu format. we report here all "on study" SAEs and treatment related AEs by SOC and PT ( PT >=1%)
 
Arm/Group Title Vinflunine Alkylating Agent
Hide Arm/Group Description

Patients randomised in the test arm (arm A) received VFL at the dose of 280 mg/m² on day 1 of each cycle every 3 weeks, over a 20-minute intravenous (IV) infusion. Cycles were repeated every 3 weeks.

vinflunine: 280 mg/m2 on day 1 of each cycle every 3 weeks

Patients randomised in the control arm (arm B) received an alkylating agent used as a single agent which was available in the investigational center and was approved for the treatment of cancer in the country.

Alkylating agent of physician choice registered in cancer: cyclophosphamide or melphalan or mitomycin C or thiotepa or cisplatin or carboplatin
All-Cause Mortality
Vinflunine Alkylating Agent
Affected / at Risk (%) Affected / at Risk (%)
Total   276/298 (92.62%)   274/296 (92.57%) 
Hide Serious Adverse Events
Vinflunine Alkylating Agent
Affected / at Risk (%) Affected / at Risk (%)
Total   82/297 (27.61%)   66/290 (22.76%) 
Blood and lymphatic system disorders     
Neutropenia † 1  6/297 (2.02%)  0/290 (0.00%) 
Anaemia † 1  6/297 (2.02%)  0/290 (0.00%) 
Febrile neutropenia † 1  3/297 (1.01%)  1/290 (0.34%) 
Thrombocytopenia † 1  1/297 (0.34%)  2/290 (0.69%) 
Endocardititis staphylococcal † 1  1/297 (0.34%)  0/290 (0.00%) 
Cardiac disorders     
Arteriospasm coronary † 1  1/297 (0.34%)  0/290 (0.00%) 
Atrial fibrillation † 1  1/297 (0.34%)  1/290 (0.34%) 
Cardiac failure † 1  0/297 (0.00%)  1/290 (0.34%) 
Gastrointestinal disorders     
Constipation † 1  5/297 (1.68%)  0/290 (0.00%) 
Vomiting † 1  6/297 (2.02%)  3/290 (1.03%) 
Abdominal pain † 1  4/297 (1.35%)  1/290 (0.34%) 
Ileus † 1  3/297 (1.01%)  0/290 (0.00%) 
Ileus paralytic † 1  3/297 (1.01%)  0/290 (0.00%) 
Stomatis † 1  3/297 (1.01%)  0/290 (0.00%) 
Intestinal obstruction † 1  2/297 (0.67%)  0/290 (0.00%) 
Nausea † 1  2/297 (0.67%)  1/290 (0.34%) 
Haematemesis † 1  1/297 (0.34%)  0/290 (0.00%) 
Abdominal pain upper † 1  1/297 (0.34%)  0/290 (0.00%) 
Dysphagia † 1  0/297 (0.00%)  1/290 (0.34%) 
Oesophagial stenosis † 1  0/297 (0.00%)  1/290 (0.34%) 
Upper gastrointestinal haemorrage † 1  1/297 (0.34%)  0/290 (0.00%) 
General disorders     
Asthenia † 1  2/297 (0.67%)  0/290 (0.00%) 
Fatigue † 1  2/297 (0.67%)  0/290 (0.00%) 
Femur fracture † 1  1/297 (0.34%)  1/290 (0.34%) 
Hepatobiliary disorders     
Hepatic function abnormal † 1  1/297 (0.34%)  0/290 (0.00%) 
Bile duct obstruction † 1  0/297 (0.00%)  1/290 (0.34%) 
Infections and infestations     
Neutropenic infections † 1  4/297 (1.35%)  1/290 (0.34%) 
Pneumonia † 1  3/297 (1.01%)  1/290 (0.34%) 
Urinary tract infection † 1  2/297 (0.67%)  2/290 (0.69%) 
Sepsis † 1  1/297 (0.34%)  1/290 (0.34%) 
Cellulitis † 1  1/297 (0.34%)  0/290 (0.00%) 
Influenza † 1  1/297 (0.34%)  0/290 (0.00%) 
Staphylococcal infection † 1  1/297 (0.34%)  0/290 (0.00%) 
Catheter related infections † 1  0/297 (0.00%)  1/290 (0.34%) 
Central line infection † 1  0/297 (0.00%)  1/290 (0.34%) 
Lobar pneumonia † 1  0/297 (0.00%)  1/290 (0.34%) 
Upper respiratory tract infection † 1  0/297 (0.00%)  1/290 (0.34%) 
Injury, poisoning and procedural complications     
Humerus fracture † 1  1/297 (0.34%)  0/290 (0.00%) 
Allergic transfusion reaction † 1  0/297 (0.00%)  1/290 (0.34%) 
Fall † 1  0/297 (0.00%)  1/290 (0.34%) 
Investigations     
Transaminases increased † 1  1/297 (0.34%)  0/290 (0.00%) 
Metabolism and nutrition disorders     
Hyponatraemia † 1  2/297 (0.67%)  0/290 (0.00%) 
Hyperglycaemia † 1  1/297 (0.34%)  1/290 (0.34%) 
Hypercalcaemia † 1  0/297 (0.00%)  1/290 (0.34%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1  1/297 (0.34%)  1/290 (0.34%) 
Myalgia † 1  1/297 (0.34%)  0/290 (0.00%) 
Bone pain † 1  0/297 (0.00%)  1/290 (0.34%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Malignant neoplasm progression † 1  38/297 (12.79%)  43/290 (14.83%) 
Cancer pain † 1  1/297 (0.34%)  0/290 (0.00%) 
Squamous cell carcinoma † 1  0/297 (0.00%)  1/290 (0.34%) 
Nervous system disorders     
Epilepsy † 1  1/297 (0.34%)  0/290 (0.00%) 
Neuralgia † 1  1/297 (0.34%)  0/290 (0.00%) 
Brachial plexopathy † 1  0/297 (0.00%)  1/290 (0.34%) 
Headache † 1  0/297 (0.00%)  1/290 (0.34%) 
Peripheral sensory neuropathy † 1  1/297 (0.34%)  0/290 (0.00%) 
Spinal cord compression † 1  0/297 (0.00%)  1/290 (0.34%) 
Psychiatric disorders     
Confusional state † 1  1/297 (0.34%)  0/290 (0.00%) 
Hallucination † 1  0/297 (0.00%)  1/290 (0.34%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism † 1  4/297 (1.35%)  2/290 (0.69%) 
Dyspnoea † 1  6/297 (2.02%)  2/290 (0.69%) 
Interstitial lung disease † 1  0/297 (0.00%)  1/290 (0.34%) 
Pleural effusion † 1  1/297 (0.34%)  1/290 (0.34%) 
Acute respiratory failure † 1  1/297 (0.34%)  0/290 (0.00%) 
Pneumonitis † 1  1/297 (0.34%)  0/290 (0.00%) 
Pulmonary hypertension † 1  1/297 (0.34%)  0/290 (0.00%) 
1
Term from vocabulary, MedDRA (12.0)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Vinflunine Alkylating Agent
Affected / at Risk (%) Affected / at Risk (%)
Total   197/297 (66.33%)   262/290 (90.34%) 
Blood and lymphatic system disorders     
Neutropenia † 1  37/297 (12.46%)  31/290 (10.69%) 
Thrombocyotopenia † 1  3/297 (1.01%)  39/290 (13.45%) 
Gastrointestinal disorders     
Constipation † 1  102/297 (34.34%)  23/290 (7.93%) 
Nausea † 1  70/297 (23.57%)  67/290 (23.10%) 
Abdominal pain † 1  66/297 (22.22%)  16/290 (5.52%) 
Stomatitis † 1  52/297 (17.51%)  18/290 (6.21%) 
Vomiting † 1  34/297 (11.45%)  33/290 (11.38%) 
Diarrhoea † 1  16/297 (5.39%)  19/290 (6.55%) 
General disorders     
Asthenia † 1  89/297 (29.97%)  43/290 (14.83%) 
Injection site reaction † 1  29/297 (9.76%)  2/290 (0.69%) 
Fatigue † 1  23/297 (7.74%)  25/290 (8.62%) 
Investigations     
Weight decreased † 1  26/297 (8.75%)  17/290 (5.86%) 
Metabolism and nutrition disorders     
Anorexia † 1  31/297 (10.44%)  24/290 (8.28%) 
Musculoskeletal and connective tissue disorders     
Myalgia † 1  38/297 (12.79%)  5/290 (1.72%) 
Arthralgia † 1  21/297 (7.07%)  3/290 (1.03%) 
Nervous system disorders     
Peripheral sensory neuropathy † 1  21/297 (7.07%)  5/290 (1.72%) 
Skin and subcutaneous tissue disorders     
Alopecia † 1  30/297 (10.10%)  9/290 (3.10%) 
1
Term from vocabulary, MedDRA (12.0)
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr Karim Keddad
Organization: INSTITUT DE RECHERCHE PIERRE FABRE
Phone: +33 5 34 50 61 69
EMail: karim.keddad@pierre-fabre.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Pierre Fabre Medicament
ClinicalTrials.gov Identifier: NCT01091168    
Other Study ID Numbers: L00070 IN 308 B0
First Submitted: February 3, 2010
First Posted: March 23, 2010
Results First Submitted: May 27, 2019
Results First Posted: September 16, 2019
Last Update Posted: September 16, 2019