Clinical Trial Results:
PAM50 HER2-enriched phenotype as a predictor of early response to neoadjuvant lapatinib plus trastuzumab in Stage I to IIIA HER2-positive breast cancer
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Summary
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EudraCT number |
2013-001036-22 |
Trial protocol |
ES |
Global end of trial date |
26 Nov 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
05 May 2022
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First version publication date |
05 May 2022
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Other versions |
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Summary report(s) |
SOLTI-1114_Sinopsys_CSR_ENG |
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 |
SOLTI-1114
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01973660 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
SOLTI
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Sponsor organisation address |
C/Balmes 89 3-7, Barcelona, Spain, 08008
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Public contact |
Investigación Clínica, SOLTI, 34 933436302, regsolti@gruposolti.org
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Scientific contact |
Investigación Clinica, SOLTI, 34 933436302, regsolti@gruposolti.org
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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 |
10 Sep 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
10 Sep 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
26 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 the ability of the PAM50 HER2-enriched (HER2-E) subtype to predict pathological complete response in the breast (pCRB) to dual HER2 blockade with lapatinib and trastuzumab, with or without endocrine therapy, at the time of surgery.
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Protection of trial subjects |
All patients received written and verbal information regarding the study. The given information emphasised that participation in the study was voluntary and that the patient could withdraw from the study at any time and for any reason. All patients were given the opportunity to ask questions about the study and were given sufficient time to decide whether to participate in the study.
Before any study-related procedures, the informed consent form was signed and personally dated by the patient (or their legally acceptable representative and/or witness, as applicable) and by the person who conducted the informed consent discussion. The consent included information that data was recorded, collected, processed and could be transferred to European Economic Area (EEA) or non-EEA countries. In accordance with the European Union Data Protection Directive (95/46/EC), the data did not identify any person taking part in the study.
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Background therapy |
At present, HER2 status is defined in the clinical setting with the IHC/ISH technique; however, in recent studies it has been seen that the clinically defined HER+ population is not biologically homogeneous and that determining gene expression profiles can identify the different intrinsic molecular subtypes53,58, that are predominantly of the HER2-E subtype in HER2+/ER- disease (50-60%) and of the luminal A/B subtype in HER2+/ER+ disease (50-60%). Thus, gene expression profiling may likely provide additional information apart from the HR status. In fact, in the XENA study, a recent, small retrospective trial, it was shown that the HER2-E subtype determined using the PAM50 platform predicts the response to the trastuzumab-based neoadjuvant chemotherapy regardless of HR status59. Moreover, the NOAH study verified that the HER2-E subtype determined by the PAM50 platform and the PAM50 ROR groups predict pCR and disease-free survival after trastuzumab-based chemotherapy58. Based on the above, we present the hypothesis that the PAM50-determined HER2-E subtype predicts the response to the neoadjuvant dual HER2 blockade, with or without endocrine therapy, in early stage HER2+ breast cancer (stage I-IIIA). | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Jul 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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: 151
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Worldwide total number of subjects |
151
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EEA total number of subjects |
151
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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) |
151
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Between October 2013 and December 2015, a total number of 216 patients were screened and signed the informed consent. Of these, 151 patients were Enrolled into the study. For the remaining 65 patients, the reasons for non-enrolment are listed in the table below, as documented in the CRF End of Selection form. | ||||||||||||||
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Pre-assignment
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Screening details |
- | ||||||||||||||
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Pre-assignment period milestones
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Number of subjects started |
151 | ||||||||||||||
Number of subjects completed |
151 | ||||||||||||||
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Period 1
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Period 1 title |
Treatment period
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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Total sample | ||||||||||||||
Arm description |
- | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Lapatinib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1000 mg; administered once daily
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Investigational medicinal product name |
Transtuzumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Loading dose of 8 mg followed by 6 mg/kg, administered every 3 weeks.
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Investigational medicinal product name |
Letrozole or Tamoxifen
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
For HR (+)
Letrozole: 2.5 mg; administered daily
Tamoxifen: 20 mg; administered daily
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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 |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
80 mg/m²; administered once weekly
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Period 2
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Period 2 title |
D-14
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Is this the baseline period? |
No | ||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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Total sample | ||||||||||||||
Arm description |
- | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Lapatinib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
1000 mg; administered once daily
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Investigational medicinal product name |
Transtuzumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Loading dose of 8 mg followed by 6 mg/kg, administered every 3 weeks.
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Investigational medicinal product name |
Letrozole or Tamoxifen
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
For HR (+)
Letrozole: 2.5 mg; administered daily
Tamoxifen: 20 mg; administered daily
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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 |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
80 mg/m²; administered once weekly
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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 |
Total sample
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Reporting group description |
- | ||
Reporting group title |
Total sample
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Reporting group description |
- | ||
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End point title |
Ability of the HER2-E subtype to predict pCR in breast | |||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Between October 2013 and December 2015, a total number of 216 patients were screened and signed the informed consent. Of these, 151 patients were Enrolled into the study.
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Statistical analysis title |
Primary efficacy endpoint | |||||||||||||||
Comparison groups |
Total sample v Total sample
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Number of subjects included in analysis |
90
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Analysis specification |
Pre-specified
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Analysis type |
equivalence | |||||||||||||||
P-value |
= 0.0004 | |||||||||||||||
Method |
Chi-squared corrected | |||||||||||||||
Parameter type |
Odds ratio (OR) | |||||||||||||||
Point estimate |
6.15
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
2.3 | |||||||||||||||
upper limit |
16.8 | |||||||||||||||
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End point title |
Ability of the HER2-E subtype to predict pCR in breast and axila | |||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Between October 2013 and December 2015, a total number of 216 patients were screened and signed the informed consent. Of these, 151 patients were Enrolled into the study
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
pCR depending on Gene expression changes | ||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
14 days
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Molecular subtype at day 14 | ||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
14 days
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
pCR rates according to changes in subtype | ||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
15 Days
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
pCR rates within HR-negative disease | ||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
14 Days
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
pCR rates within HR+ disease | ||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
14 days
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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 |
During treatment
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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 |
21.1
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Reporting groups
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Reporting group title |
Total Sample
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 2% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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20 Nov 2013 |
• Expand the centers participating in this study.
• Update the ASCO / CAP guidelines for determining HER2, which are used for patient selection.
• Add one inclusion criteria for multifocal patients.
• Add an inclusion criterion specifying that patients who do not have sufficient sample for the PAM50 analysis (main study objective) and do not want to be re-biopsied will not be enrolled in the study.
• Specify the windows allowed for the different test evaluations.
• Change the WHO tumor response assessment criteria to RECIST 1.1 because they are the most used by the centers participating in the trial.
• Correct the platform to be used for genomic analysis. It is the same gene bank (PAM50) but it is not the version sold under the name ProsignaTM. This is another version that is marketed for use in research only.
• Eliminate the independent data monitoring committee (CIMD), since only the Steering Committee of the study will eventually be formed.
• Add bibliography relevant to the justification of the study.
• Writing and typographical corrections.
• Correct the information sheet to the patient according to the changes described above and specify the tests that are performed before the surgery. A new version of informed consent is generated (version 3.0 of November 20, 2013). |
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17 Nov 2014 |
• Protocol version 4.0 dated November 17, 2014 is generated and a new patient information sheet and informed consent for the assignment of surplus samples obtained in the PAMELA study, version 1.0 dated November 17, 2014. |
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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 | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/32938620 |
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