Clinical Trial Results:
PERtuzumab-trastuzumab plus lEetrozoLe In endocrine Sensitive breast cancer: a phase II neoAdjuvant study
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Summary
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EudraCT number |
2013-002662-40 |
Trial protocol |
IT |
Global end of trial date |
12 Jan 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Nov 2022
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First version publication date |
01 Nov 2022
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Other versions |
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Summary report(s) |
Medica Journal article |
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 |
AS.T.R.O.BC01-13
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
ASTRO Association for Translational research in Oncology.
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Sponsor organisation address |
Via G. Mameli 3/1, Genova, Italy, 16122
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Public contact |
Gian Luca De Salvo, Istituto Oncologico Veneto, 0039 0498215704, clinical.trial@ioveneto.it
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Scientific contact |
Gian Luca De Salvo, Istituto Oncologico Veneto, 0039 0498215704, clinical.trial@ioveneto.it
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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 |
01 Jul 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
12 Jan 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
12 Jan 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 rate of pathologic complete response (pCR), as defined as complete disappearance of invasive tumor in breast and axillary nodes
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Protection of trial subjects |
The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Council for Harmonisation (ICH) guideline E6: Good Clinical Practice (GCP).
As applicable according to local regulations, the protocol and all protocol amendments were reviewed and approved by Italian Competent Authority AIFA.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
01 Sep 2013
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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 |
Italy: 44
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Worldwide total number of subjects |
44
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EEA total number of subjects |
44
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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) |
22
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From 65 to 84 years |
22
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85 years and over |
0
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Recruitment
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Recruitment details |
From January 2014 to July 2017, 64 patients from 8 Institutions were enrolled, and 61 were evaluable for molecular response after 2 weeks of letrozole treatment; after the molecular evaluation 44 patients were considered for the analysis. | ||||||
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Pre-assignment
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Screening details |
Patients were included in the study only if they met all the following criteria - female patients with primary diagnosis of infiltrating breast cancer - HR positivity (ER ≥ 10% and/or PgR ≥10%) and HER2 positivity (IHC 3+ or FISH/CISH amplification) as assessed by local laboratory - Stage II-IIIA - age >18 yrs - ECOG Performance Status 0-1 | ||||||
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Period 1
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Period 1 title |
Overall trial (overall 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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Trastuzumab+Pertuzumab | ||||||
Arm description |
Trastuzumab+Pertuzumab for the molecular responders should be administered for five 21-day cycles prior to surgery, that should be performed within 3 weeks from the last iv therapy infusion. | ||||||
Arm type |
single arm | ||||||
Investigational medicinal product name |
Pertuzumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Pertuzumab was administered as an intravenous infusion on Day 1 of the first treatment cycle as a loading dose of 840 mg. The following 4 courses were administered at the dose of 420 mg on Day 1 every 3 weeks.
Initial infusions of pertuzumab was administered over 60 (± 10) minutes and patients observed for 60 minutes from the end of infusion for infusion-related symptoms such as fever, chills, hypotension, shortness of breath, skin rash, headache, nausea and/or vomiting.
Interruption or slowing of the infusion could be made to reduce such symptoms. If the infusion was well tolerated, subsequent infusions could be administered over 30 to 60 (± 10) minutes, with patients observed for a further 30 minutes.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
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Subject analysis sets
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Subject analysis set title |
Pertuzumab+Trastuzumab
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Molecular responders
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End points reporting groups
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Reporting group title |
Trastuzumab+Pertuzumab
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Reporting group description |
Trastuzumab+Pertuzumab for the molecular responders should be administered for five 21-day cycles prior to surgery, that should be performed within 3 weeks from the last iv therapy infusion. | ||
Subject analysis set title |
Pertuzumab+Trastuzumab
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Molecular responders
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End point title |
Number of pCR in responder patients | |||||||||
End point description |
Pathologic response:
A pathologic complete response (pCR) was defined the complete absence of infiltrating tumor cells in the breast and in the lymph nodes. Residual in situ disease (DCIS) was included in the pCR category.
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End point type |
Primary
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End point timeframe |
From the end of Screening to Surgery
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| Notes [1] - workaround for single arm submission |
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Statistical analysis title |
Efficacy results | |||||||||
Statistical analysis description |
Sixty-four patients were enrolled, 44 were classified as molecular responders. All these patients completed the assigned treatment with letrozole-trastuzumab-pertuzumab and underwent surgery. A pCR was observed in 9/44 cases (20.5%, 95%CI 11.1%-34.5%).
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Comparison groups |
Trastuzumab+Pertuzumab v Pertuzumab+Trastuzumab
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Number of subjects included in analysis |
88
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Analysis specification |
Pre-specified
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Analysis type |
other [2] | |||||||||
P-value |
≤ 0.05 | |||||||||
Method |
Wilson score method | |||||||||
Confidence interval |
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| Notes [2] - A phase II study in order to estimate the rate of pCR after use of Trastuzumab +Pertuzumab |
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Adverse events information
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Timeframe for reporting adverse events |
from 1st dose of Pertuzumab to withdrawal of therapy/Study conclusion
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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 |
22
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Reporting groups
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Reporting group title |
safety evaluable population
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Reporting group description |
all subjects enrolled in the study who received at least 1 dose of the investigational study treatment (ie, pertuzumab). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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15 Jan 2014 |
Amendment 1, dated 15 Jan 2014, was implemented due to administrative reasons (adding of one clinical centre and change of one local PI) and to accomplish with the Competent Authority suggestions. This amendement specified the following modifications:
In the paragraph 5.6 Pre-study, concomitant, and post-study treatment(s), the text: “Any oral, injected or implanted hormonal methods of contraception” was changed with “Hormonal replacement therapy”
- In the paragraph 6.3 “LVEF ≤ 50%” was changed with “LVEF ≤ 45%”
- Pertuzumab and trastuzumab could be administered on the same day (day 1) if no reactions at cycle 1 for the following 4 cycles.
- The centre of Vicenza was added and the PI of the Milan INT centre was changed from prof. De Braud to dr Giulia Bianchi |
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01 Jul 2016 |
Amendment 2, dated 01 July 2016, was implemented to prolong the recruitment period of the study due to the trend registered until then that was slower than expected. Moreover, there were some changes in the participating centres. A new version of the pertuzumab IB was implemented. This amendement specified the following modifications:
- Recruitment period prolonged from 24 to 44 months
- Estimated date of last subject completed from March 2016 to October 2017
- Changes in the number and list of participating centres: from 12 to 10 clinical centres. Aviano and Trento were added, Pisa and Candiolo were excluded.
- Investigator’s Brochure of Perejeta Ed. 14_02/2015 was implemented |
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01 Jun 2017 |
Amendment 3, dated 01 June 2017, was implemented to further prolong the recruitment period of the study. Moreover, there was an update in the translational section of the study, with some changes in the planned analyses. A new version of the pertuzumab IB was implemented. Finally, some administrative changes were implemented, change of the sponsor legal representative amd changes in the participating centres. This amendement specified the following modifications:
- Change of legal representative of the sponsor from prof. Conte to dr Bengala
- Recruitment period prolonged from 44 to 52 months
- Change of the estimated date of last subject completed from October 2017 to May 2018
- Changes in the translational biomarker analyses eliminating the analysis of pAKT and adding a panel of other relevant cancer-realted genes, pTEN, tumor infiltrating lymphocytes
- Changes in the list of the participating centres: Verona e Vicenza were excluded. Change of the PI of Udine from dr Puglisi to dr Russo
- Investigator’s Brochure of Perejeta Ed. 16_02/2017 was implemented |
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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 | |||
