Clinical Trial Results:
Phase II study evaluating oral vinorelbine as a single agent in patients with hormone receptor breast cancer with bone metastases previously treated by a hormone therapy
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Summary
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EudraCT number |
2009-014497-18 |
Trial protocol |
FR AT IT ES |
Global end of trial date |
17 Jun 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
31 Jan 2019
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First version publication date |
31 Jan 2019
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
PM0259 CA 228 BO
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Pierre Fabre Médicament
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Sponsor organisation address |
45 place Abel Gance, Boulogne, France, 92100
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Public contact |
Gustavo VILLANOVA M.D
Oncology Medical Affairs Department, Pierre Fabre Médicament, +33 (0)149108265, gustavo.villanova@pierre-fabre.com
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Scientific contact |
Gustavo VILLANOVA M.D
Oncology Medical Affairs Department, Pierre Fabre Médicament, +33 (0)149108265, gustavo.villanova@pierre-fabre.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
16 Mar 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
09 May 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Jun 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To determine the Progression-Free Survival (PFS) of oral vinorelbine as a single agent in patients with hormone receptor positive breast cancer with bone metastases previously treated by a hormone therapy.
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Protection of trial subjects |
This study was conducted in accordance with the ethical principles that have their origin in the current Declaration of Helsinki and was consistent with International Conference on Harmonization Good Clinical Practice (ICH GCP) and applicable regulatory requirements. The study was conducted in compliance with the protocol. The protocol, amendments, and the subject informed consent received Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approval/favourable opinion prior to initiation of the study and/or their implementation.
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Background therapy |
Prophylactic oral anti-emetic medication with a 5-HT3 antagonist was recommended before each oral vinorelbine administration. Oral antiemetic treatments were provided to the patients at home. The use of corticosteroids as anti-emetic treatment was allowed. Patients had to receive full supportive care including antibiotics, antidiarrhoeals, analgesics, transfusion of blood products, when appropriate. The use of drugs with laxative properties had to be avoided. Prophylactic use of Colony Stimulating Factor (CSF) was allowed during the study treatment. Granulocyte stimulating growth factors could be given to patients who experienced febrile neutropenia, grade 4 asymptomatic neutropenia or neutropenic infection according to institutional rules. Patients had to be under treatment by a bisphosphonate since at least one month before entering the study. | ||
Evidence for comparator |
No control arm was planned as the study aimed at evaluating the clinical benefit of oral vinorelbine in patients suffering from bone metastases from breast cancer after failure to hormone therapy. | ||
Actual start date of recruitment |
14 Apr 2010
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy, Safety, Scientific research | ||
Long term follow-up duration |
3 Years | ||
Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Mexico: 13
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Country: Number of subjects enrolled |
Russian Federation: 7
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Country: Number of subjects enrolled |
Poland: 8
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Country: Number of subjects enrolled |
Spain: 1
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Country: Number of subjects enrolled |
Austria: 17
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Country: Number of subjects enrolled |
France: 18
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Country: Number of subjects enrolled |
Italy: 6
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Worldwide total number of subjects |
70
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EEA total number of subjects |
50
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
46
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From 65 to 84 years |
24
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 70 patients with hormone receptor positive breast cancer with bone metastases previously treated by a hormone therapy were enrolled and received at least one dose of study treatment. | ||||||||||||||||||||||
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Pre-assignment
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Screening details |
No further information | ||||||||||||||||||||||
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Period 1
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Period 1 title |
Treatment period (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||
Blinding implementation details |
The study was an open label non-randomized trial.
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Arms
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Arm title
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Vinorelbine arm | ||||||||||||||||||||||
Arm description |
Patients were included after written informed consent was obtained and all screening assessments have been performed. | ||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||
Investigational medicinal product name |
Vinorelbine
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Investigational medicinal product code |
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Other name |
Navelbine
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Pharmaceutical forms |
Capsule, soft
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Routes of administration |
Oral use
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Dosage and administration details |
Patients received Oral vinorelbine single agent at the dose of 60 mg/m² weekly at the first cycle (1 cycle = 4 weeks of treatment) then at the increased dose of 80 mg/m² at cycle 2 and subsequent cycles in the absence of a grade 3 or grade 4 neutropenia. Oral vinorelbine was given on days 1, 8, 15 and 22 of a cycle. Patients had to receive at least 3 cycles of treatment unless documented disease progression, unacceptable toxicity or patient refusal. Vinorelbine was supplied as soft capsules that had to be rapidly swallowed with a glass of water without chewing or sucking them. It was recommended to take the capsules with some food. The treatment was administered on an outpatient setting. However, the patient had to return to the hospital at Day 1 of each cycle to receive study drugs at the hospital under the supervision of the investigator. The study medication had to be stored refrigerated (2°C to 8°C) and protected from light in the original closed container.
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Baseline characteristics reporting groups
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Reporting group title |
Treatment period
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Reporting group description |
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End points reporting groups
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Reporting group title |
Vinorelbine arm
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Reporting group description |
Patients were included after written informed consent was obtained and all screening assessments have been performed. | ||
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End point title |
Progression-free survival [1] | ||||||||
End point description |
PFS was estimated on the ITT population (all treated patients) using Kaplan Meier curves and Confidence intervals on the median PFS were calculated using the reflected method. Patients lost to follow-up, or without a known record of progression or death at the time of analysis had the progression-free survival censored at the date of last tumour assessment or last contact of a follow-up showing no progression, whichever occurred last.
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End point type |
Primary
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End point timeframe |
PFS was calculated from the registration date until the date of progression or death due to any cause if no progression was recorded first. Median duration of follow-up at final analysis was 43.3 months.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis can be added because the study is a single-arm study. |
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Attachments |
Kaplan Meier estimates of PFS |
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| No statistical analyses for this end point | |||||||||
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End point title |
Clinical benefit rate | ||||||||
End point description |
The clinical benefit rate is defined as the percentage of confirmed CR, confirmed PR and stabilization for at least 24 weeks observed in the ITT population.
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End point type |
Secondary
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End point timeframe |
The clinical benefit rate was evaluated unitl the date of progression or death due to any cause if no progression was recorded first.
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall response rate | ||||||||||||||||||
End point description |
Overall Response Rate (ORR) was defined as the sum of CR and PR rate (using the best confirmed response recorded from the date of randomisation to the end of treatment) in the ITT population, according to investigator assessment.
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End point type |
Secondary
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End point timeframe |
Overall Response Rate (ORR) was evaluated from the randomisation to the end of treatment
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Overall survival (OS) | ||||||||
End point description |
Analyses of Overall Survival were performed with the Kaplan-Meier method. Overall survival of patients lost to follow-up or without a known record of death was censored at the date of last news. At DCO, 38 patients (54%) have died (35 from progression, 3 from other reason and 3 have been lost to follow-up). The remaining 29 patients were still alive.
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End point type |
Secondary
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End point timeframe |
Overall Survival was evaluated from the date of registration to the date of death due to any cause in the ITT population. Median duration of follow-up at final analysis was 43.3 months.
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Attachments |
Kaplan-Meier Survival Time |
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End point title |
Duration of disease control | ||||||||
End point description |
The disease control rate (sum of confirmed CR, confirmed PR and stabilisation rate) were evaluated for the ITT population.
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End point type |
Secondary
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End point timeframe |
The duration of disease control (CR, PR and stabilization of at least 24 weeks) was measured from the date of registration until the criteria for disease progression is met or the date of death or start of new anticancer therapy.
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Each patient was assessed for occurrence of AEs throughout the study period (starting after the 1st dose of study medication and up to and including 30 days after the last dose). At DCO, all patients have discontinued (med duration: 5.8 (0.9-18.4)months).
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Adverse event reporting additional description |
Any AE occurring during the study period, spontaneously reported by the patient or observed by others, was recorded in the CRF. The relative dose intensity was 83.0% [22.9-108.2]. More than 1/3 of the patients received more than 90% of the planned dose. The median number of cycles was 6 (1-18).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
12.1
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Reporting groups
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Reporting group title |
Safety population
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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01 Apr 2010 |
- Allow intake of oral vinorelbine at home at Day 8, Day 15, and Day 22 of every cycle.
- Update to the name of the Clinical Pharmacy Responsible Person for the study.
- Prolongation of the patient enrolment period until Q2 2011.
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01 Apr 2010 |
- Allow intake of oral vinorelbine at home at Day 8, Day 15, and Day 22 of every cycle.
Information added to the master ICF
- Modalities of dispensation of the study treatment at Day 1 of each cycle
- Modalities of storage of study treatment at the patient’s home.
- Procedure for administration of Navelbine Oral (blood tests, agreement of the investigator before each intake at home)
- Completion of a patient diary
- Modalities of return of remaining capsules or empty blisters. - Improve the information given regarding the examinations to be followed by the patient and the person in charge of the study treatment at each study site.
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10 May 2010 |
Update of the Investigator’s list |
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22 Feb 2011 |
- Allow inclusion of patients with unknown HER2 status.
- Prolongation of the patient enrolment period until 31-Mar-2012.
- Update the name of the Clinical Trial Coordinator and the address of the Clinical Pharmacy.
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17 Oct 2011 |
Update of the Investigator’s list |
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25 Sep 2013 |
Update of the Investigator’s list |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
