Clinical Trial Results:
A randomized phase II pilot study to evaluate safety and efficacy of the addition of vismodegib to standard neoadjuvant chemotherapy in triple negative breast cancer patients.
Summary
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EudraCT number |
2014-001287-35 |
Trial protocol |
ES |
Global end of trial date |
13 Nov 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Sep 2021
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First version publication date |
24 Sep 2021
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Other versions |
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Summary report(s) |
SPANISH REPORT |
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 |
SHH-CM
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02694224 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Clínica Universidad de Navarra
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Sponsor organisation address |
Avda. Pío XII,36, Pamplona, Spain, 31008
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Public contact |
UCICEC, Clinica Universidad de Navarra, 34 948 25 54 00 1144, ucicec@unav.es
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Scientific contact |
UCICEC, Clinica Universidad de Navarra, 34 948 25 54 00 1144, ucicec@unav.es
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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 |
09 Apr 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
13 Nov 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Nov 2018
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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 evaluate safety and efficacy of vismodegib with standard neoadjuvant chemotherapy in breast cancer patients based on the CTCAE v4 2010 scale.
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Protection of trial subjects |
NA
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Jul 2015
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Long term follow-up planned |
No
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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 |
Spain: 28
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Worldwide total number of subjects |
28
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EEA total number of subjects |
28
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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) |
25
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
Woman between 18 and 75 years. | |||||||||||||||
Pre-assignment
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Screening details |
Patients diagnosed with breast cancer (stages I-III) with triple negative subtype, who have not previously received chemotherapy or systemic therapy. In these patients, treatment with neoadjuvant chemotherapy established in the protocol is indicated. | |||||||||||||||
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 |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Experimental group | |||||||||||||||
Arm description |
19 patients were randomized, of whom 18 completed the treatment phase. These patients were administered the usual neoadjuvant treatment of Paclitaxel, sequenced to epirubicin and cyclophosphamide in combination with Vismodegib. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Vismodegib
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Investigational medicinal product code |
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Other name |
Erivedge
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
150 mg/day orally during the paclitaxel stage.
Vismodegib will be administered daily for 12 weeks (84 days), coinciding with the duration of paclitaxel treatment (21-day cycles, with administration on days 1, 8 and 15 of the cycle, 12 administrations).
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Arm title
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Control group | |||||||||||||||
Arm description |
10 patients were randomized, of whom 9 completed the treatment. These patients are given neoadjuvant treatment of paclitaxel sequenced to epirubicin plus cyclophosphamide. Two to three weeks would pass between the last cycle of paclitaxel and the start of anthracyclines. | |||||||||||||||
Arm type |
Active comparator | |||||||||||||||
Investigational medicinal product name |
Paclitaxel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Infusion
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Dosage and administration details |
Weekly administration at a dose of 80 mg/m2 intravenously on days 1, 8 and 15 of each 21-day cycle (for 12 weeks).
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Investigational medicinal product name |
Epirubicina
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Injection
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Dosage and administration details |
Intravenous route at a dose of 90 mg/m2. A total of 4 doses will be received every 2 weeks with granulocyte and monocyte factor support. Administered in combination with cyclophosphamide to all randomized patients.
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Investigational medicinal product name |
Ciclofosfamide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder and solution for solution for injection
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Routes of administration |
Injection
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Dosage and administration details |
Intravenous route at a dose of 600 mg/m2. A total of 4 doses will be received every 2 weeks with granulocyte and monocyte factor support. It is administered in combination with epirubicin to all randomized patients.
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Baseline characteristics reporting groups
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Reporting group title |
Experimental group
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Reporting group description |
19 patients were randomized, of whom 18 completed the treatment phase. These patients were administered the usual neoadjuvant treatment of Paclitaxel, sequenced to epirubicin and cyclophosphamide in combination with Vismodegib. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control group
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Reporting group description |
10 patients were randomized, of whom 9 completed the treatment. These patients are given neoadjuvant treatment of paclitaxel sequenced to epirubicin plus cyclophosphamide. Two to three weeks would pass between the last cycle of paclitaxel and the start of anthracyclines. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Experimental group
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Reporting group description |
19 patients were randomized, of whom 18 completed the treatment phase. These patients were administered the usual neoadjuvant treatment of Paclitaxel, sequenced to epirubicin and cyclophosphamide in combination with Vismodegib. | ||
Reporting group title |
Control group
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Reporting group description |
10 patients were randomized, of whom 9 completed the treatment. These patients are given neoadjuvant treatment of paclitaxel sequenced to epirubicin plus cyclophosphamide. Two to three weeks would pass between the last cycle of paclitaxel and the start of anthracyclines. |
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End point title |
Safety and efficacy | |||||||||||||||
End point description |
Efficacy is analyzed by pathological complete response (pCR), which is determined by Miller & Paine calssification evaluated after surgery. In the control group 67% of patients were found to have a pCR, while in the experimental group 56% of patients obtained pCR. Fisher's exact test was used to determine a possible relationship between the group and having pCR or not. A p-value = 0.69 was obtained, which is not significant, so there is no statistical evidence to affirm that there are differences between the two variables.
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End point type |
Primary
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End point timeframe |
Markers of safety ans efficacy will be collected whith each systemic therapy. Toxicity will be evaluated based on CTCAE v4 2010 scale.
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Statistical analysis title |
Relationship between groups | |||||||||||||||
Comparison groups |
Experimental group v Control group
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Number of subjects included in analysis |
27
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||||||||
P-value |
≤ 0.05 | |||||||||||||||
Method |
Fisher exact | |||||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
The description of AEs was coded using the PT and SOC level of the MedDRA medical dictionary version 22.0.
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Adverse event reporting additional description |
The CRF records the description, start date, end date, intensity, relationship with treatment, expected, evolution, action taken and whether the adverse events are serious or not.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22.0
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Reporting groups
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Reporting group title |
Experimental group
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Reporting group description |
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Reporting group title |
Control group
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Reporting group description |
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Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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30 Mar 2016 |
new protocol version, Version 3 |
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21 Sep 2016 |
new protocol version. Version 4 |
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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 |