Clinical Trial Results:
An Open-Label Phase 2 Study to Characterize Colon Pathology in Patients With HER2 Amplified Breast Cancer Treated With Neratinib
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Summary
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EudraCT number |
2019-001896-35 |
Trial protocol |
PT |
Global end of trial date |
28 Dec 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
08 Jan 2023
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First version publication date |
08 Jan 2023
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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 |
PUMA-NER-6203
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04366713 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Puma Biotechnology, Inc.
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Sponsor organisation address |
10880 Wilshire Blvd, Suite 2150, Los Angeles, United States, 90024
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Public contact |
Clinical Trial Management, Puma Biotechnology, Inc, +1 4242486500, clinicaltrials@pumabiotechnology.com
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Scientific contact |
Clinical Trial Management, Puma Biotechnology, Inc, +1 4242486500, clinicaltrials@pumabiotechnology.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 |
31 Jan 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
28 Dec 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Dec 2021
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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 characterize and understand colon pathogenesis related to neratinib-induced diarrhea through biopsies and images obtained by colonoscopy study.
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Protection of trial subjects |
Study commencement required prior written approval of a properly constituted Independent Ethics Committee (IEC). Clinical trial data were monitored at regular intervals by the Sponsor or their representative throughout the study to verify compliance to study protocol, completeness, accuracy and consistency of the data and adherence to local regulations on the conduct of clinical research. Patients were discontinued from investigational product(s) (IP) in the following circumstances: if patient required more than two dose reductions of neratinib, disease recurrence, initiation of alternative anti-cancer therapy, pregnancy, investigator request, patient request, or adverse event/toxicity.
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Background therapy |
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Evidence for comparator |
- | ||
Actual start date of recruitment |
31 Dec 2019
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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 |
Portugal: 6
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Worldwide total number of subjects |
6
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EEA total number of subjects |
6
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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) |
5
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||
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Pre-assignment
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Screening details |
Screening activities are to be conducted within 28 days prior to Cycle 1/Day 1, except for serum or urine pregnancy test for women of child-bearing potential, which should be performed, both, at screening and repeated within 72 hours prior to C1D1. Documentation of locally assessed ERBB2-amplified status by FISH or IHC(3+) must be confirmed. | ||||||||||||||
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Period 1
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Period 1 title |
Treatment (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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Neratinib | ||||||||||||||
Arm description |
All treated patients | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Neratinib
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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 |
All patients will receive neratinib for the first 28 days as a single daily dose of 240mg. For patients being treated for stage 1 to 3c breast cancer in the extended adjuvant setting, neratinib will
continue to be administered at a single daily dose of 240 mg until completion of one year of therapy from start of treatment, or until disease recurrence (as determined by the Investigator), death, unacceptable toxicity, or other specified withdrawal criterion.
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Investigational medicinal product name |
Capecitabine
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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 patients being treated for metastatic breast cancer (mBC), capecitabine will be introduced after the second study colonoscopy procedure at a dose of 750mg/m2 twice daily for 14 days of each 21 day treatment cycle, with neratinib administered continuously throughout at 240mg daily, until disease progression, death, unacceptable toxicity, or other specified withdrawal criterion
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Baseline characteristics reporting groups
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Reporting group title |
Treatment
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Reporting group description |
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End points reporting groups
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Reporting group title |
Neratinib
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Reporting group description |
All treated patients | ||
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End point title |
Changes in Colon Pathology [1] | ||||||||||
End point description |
Change from baseline in pathological findings in colon biopsies after the first 28 days of neratinib treatment.
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End point type |
Primary
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End point timeframe |
From baseline to 28 days after neratinib treatment
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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 formal statistical analyses were planned or conducted. All results are descriptive. |
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| Notes [2] - Number of patients with two colonocopies |
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End point title |
Incidence and Severity of Diarrhea | ||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
For first 28 days of neratinib treatment
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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 |
From time of first dose, through 28 days after last dose, assessed up to 16 months.
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Adverse event reporting additional description |
Safety population: Participants receiving at least 1 dose of investigational product.
Serious and Non-serious Adverse Events were monitored/assessed only in the safety population.
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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 |
20.0
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Reporting groups
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Reporting group title |
Neratinib
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Reporting group description |
Neratinib | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? No | |||
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 | |||
