HER2 Amplified Breast CancerPhase 2NCT04366713
A Study to Characterize Colon Pathology in Patients With HER2 Amplified Breast Cancer Treated With Neratinib
A Phase 2 study testing Neratinib, Capecitabine and Loperamide in people with HER2 Amplified Breast Cancer, run by Puma Biotechnology, Inc. at 1 site in Portugal.
Trial summary
This study will investigate colon pathology in patients with HER2-positive breast cancer treated with neratinib. Colonoscopy will be performed after eligibility has been confirmed, prior to administration of the first dose of neratinib, and after 28 days of neratinib treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HER2 Amplified Breast Cancer
- What is being tested?
- Neratinib, Capecitabine and Loperamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 sitePortugal
- Study dates
- 30 Jun 2020to 28 Dec 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged ≥18 years.
- Histologically confirmed stage 1 through stage 4 primary adenocarcinoma of the breast.
- Documented HER2 overexpression or gene-amplified tumor by a validated approved method.
- Participants with confirmed stage 1 to stage 3c breast cancer receiving extended adjuvant treatment with neratinib monotherapy must have completed a course of prior adjuvant trastuzumab or experienced side effects that resulted in early discontinuation of trastuzumab that have since resolved.
- Participants with mBC must have had at least 2 prior HER2-directed regimens.
- Left ventricular ejection fraction (LVEF) ≥50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).
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- Eastern Cooperative Oncology Group (ECOG) status of 0 to 1.
- Negative β-human chorionic gonadotropin (hCG) pregnancy test for premenopausal women of reproductive capacity (those who are biologically capable of having children) and for women less than 12 months after menopause. [Women are considered postmenopausal if they are ≥12 months without menses, in the absence of endocrine or anti-endocrine therapies.]
- Women of childbearing potential must agree and commit to the use of a highly effective non-hormonal method of contraception, i.e., intrauterine device, bilateral tubal ligation, vasectomized partner, or abstinence (only when it is the preferred lifestyle of the participant), from the time of informed consent until 28 days after the last dose of the investigational products. Men (male participant) with a female partner of childbearing potential must agree and commit to use condom and the female partner must agree and commit to use a highly effective method of contraception (i.e., any of the above methods, or for females, hormonal contraception associated with inhibition of ovulation) while on treatment and for 3 months after last dose of investigational products.
- Recovery (i.e., to Grade 1 or baseline) from all clinically significant adverse events related to prior therapies (excluding alopecia, neuropathy, and nail changes).
- No major bleeding diathesis or use of anticoagulants that would pose a high risk for endoscopic procedure.
- Provide written, informed consent to participate in the study and follow the study procedures.
Who cannot join
- Participants with confirmed stage 1 to stage 3c currently receiving chemotherapy, radiation therapy, immunotherapy, or biotherapy for breast cancer.
- Participants with mBC who have received prior capecitabine or HER2 directed tyrosine kinase inhibitor (TKI) therapy.
- Currently using drugs that have been implicated as causing microscopic colitis/watery diarrhea, such as acarbose, aspirin, proton pump inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), histamine H2 receptor antagonists, selective serotonin reuptake inhibitors, and ticlopidine (Pardi, 2017).
- Major surgery within <28 days of starting treatment or received chemotherapy, investigational agents, or other cancer therapy, except hormonal therapy (e.g., tamoxifen, aromatase inhibitors), <14 days prior to the initiation of investigational products.
- Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of ≥2; including individuals who currently use digitalis, beta-blockers, or calcium channel blockers specifically for congestive heart failure), unstable angina, myocardial infarction within 12 months of enrollment, or ventricular arrhythmia.
- Corrected QT Interval (QTc) interval >0.450 seconds (males) or >0.470 (females), or known history of QTc prolongation or Torsade de Pointes (TdP).
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- Diagnosis of inflammatory bowel disease
- Screening laboratory assessments outside the following limits:
- Laboratory Parameters Required Limit for Exclusion Absolute neutrophil count (ANC) <1,000/µl (<1.0 x 109/L) Platelet count <50,000/µl (<100 x 109/L) Hemoglobin <8 g/dL (transfusions allowed) Transfusions must be at least 14 days prior to initiation of treatment Total bilirubin >1.5 x institutional upper limit of normal (ULN) (in case of known Gilbert's syndrome, <2 x ULN is allowed) Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >2.5 x institutional ULN (>5 x ULN if liver metastases are present) Creatinine Creatinine clearance <30 mL/min (as calculated by Cockcroft-Gault formula A or Modification of Diet in Renal Disease formula B) International Normalized Ratio (INR) >1.5 a Cockcroft and Gault, 1976 b Levey et al, 1999
- Active, unresolved infections.
- Participants with a second malignancy, other than adequately treated non-melanoma skin cancers, in situ melanoma or in situ cervical cancer. Participants with other non-mammary malignancies must have been disease free for at least 5 years.
- Currently pregnant or breast-feeding.
- Significant chronic gastrointestinal disorder with diarrhea as a major symptom (eg, Crohn's disease, malabsorption, or Grade ≥2 National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events Version 4.0 [CTCAE v.4.0] diarrhea of any etiology at baseline).
- Clinically active infection with hepatitis B or hepatitis C virus.
- Evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness/social situations that could, in the Investigator's judgment, make the person inappropriate for this study.
- Known hypersensitivity to any component of the investigational products; known allergies to any of the medications or components of medications used in the trial.
- Unable or unwilling to swallow tablets
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-Label Phase 2 Study to Characterize Colon Pathology in Patients With HER2 Amplified Breast Cancer Treated With Neratinib
This study will investigate colon pathology in patients with HER2-positive breast cancer treated with neratinib. Colonoscopy will be performed after eligibility has been confirmed, prior to administration of the first dose of neratinib, and after 28 days of neratinib treatment.
Read the detailed description
This is an open-label, phase 2 study that will investigate colon pathology in patients with HER2-positive breast cancer treated with neratinib as monotherapy.
All patients will receive neratinib for the first 28 days as a single daily dose of 240 mg.
Colonoscopy will be performed after eligibility has been confirmed, but prior to administration of the first dose of neratinib and at Day 30 (± 3 days) the conclusion of Cycle 1 (28 days).
Following the second study colonoscopy procedure:
- 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.
- 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 240 mg daily, until disease progression, death, unacceptable toxicity, or other specified withdrawal criterion.
All patients will receive loperamide diarrhea prophylaxis daily for one 28-day cycle and then as needed.
- Conditions
- HER2 Amplified Breast Cancer
- Being tested
- Neratinib, Capecitabine, Loperamide
- Keywords
- HER2-Positive, Breast Cancer, Colon Pathology, Colonoscopy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NeratinibDrug
Also called Nerlynx
Administered orally once daily as a single daily dose of 240 mg
CapecitabineDrug
Administered orally twice daily at 750 mg/m^2 for 14 days of each 21 day treatment cycle
LoperamideDrug
Administered orally for prophylaxis for 28 days and then as needed
| Study group | Role | What they receive |
|---|---|---|
| Neratinib | Experimental | Neratinib with loperamide prophylaxis, and capecitabine for participants treated for metastatic breast cancer Receives: Drug: Neratinib; Drug: Capecitabine; Drug: Loperamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Colon Pathology
The primary endpoint is to describe the changes in colon pathology between the baseline colonoscopy and the second colonoscopy.
Measured: From baseline to second colonoscopy, which is 88 days after start of neratinib treatment.
Secondary outcomes (1)
Incidence and Severity of Diarrhea
Incidence and severity of treatment emergent (TEAE) diarrhea will be summarized according to the NCI-CTCAE version 4.0 in the first cycle of neratinib treatment, which is from the time of the first colonoscopy to the second colonoscopy, or 28 days for subjects with only one colonoscopy. Incidence is defined as the number of patients experiencing diarrhea divided by the number of patients at risk.
Measured: From baseline to second colonoscopy, which is 88 days after start of neratinib treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2020
- Study start30 Jun 2020
- Primary completion28 Dec 2021
- Study completion28 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HER2 Amplified Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Puma Biotechnology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chief Scientific Officer, Study director, Puma Biotechnology, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04366713
- Sponsor's protocol ID
- PUMA-NER-6203
- Other IDs
- 2019-001896-35, 2019
- Status last verified
- Jan 2023
- First submitted
- 23 Mar 2020
- Last updated
- 10 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Puma Biotechnology is committed to sharing clinical trial data and information to help physicians and patients make informed treatment decisions, and to help qualified researchers advance scientific knowledge. In accordance with legal and regulatory requirements, Puma publishes study protocol information and clinical study results on clinical trial registries, including ClinicalTrials.gov and EU Clinical Trials Register. Puma also publishes information about clinical studies in peer-reviewed scientific journals and shares data in scientific meetings. Puma commits to safeguarding confidentiality and patient privacy throughout the clinical trial data and information sharing process. Any patient-level data will be anonymized to protect personally identifiable information. Qualified researchers and study participants may submit requests for other study documentation and clinical trial data to clinicaltrials@pumabiotechnology.com for consideration.
Publications
Bowen J, Braga S, Zotto VD, Finnie J, DiPrimeo D, Cooke B, Bischof GF, Wong A, Di Palma JA. Preclinical and clinical evaluation through serial colonoscopic evaluation of neratinib-induced diarrhea in HER2-positive breast cancer-A pilot study. Physiol Rep. 2024 Aug;12(16):e70008. doi: 10.14814/phy2.70008.
PubMed 39187401
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Phase 2 Study to Characterize Colon Pathology in Patients With HER2 Amplified Breast Cancer Treated With Neratinib
- ClinicalTrials.gov ID
- NCT04366713
- Acronym / sponsor ID
- PUMA-NER-6203
- Conditions
- HER2 Amplified Breast Cancer
- Keywords
- HER2-Positive, Breast Cancer, Colon Pathology, Colonoscopy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Puma Biotechnology, Inc.Industry (pharma, biotech, devices)
- Study start
- 30 Jun 2020 (actual)
- Primary completion
- 28 Dec 2021 (actual)
- Study completion
- 28 Dec 2021 (actual)
- First posted
- 29 Apr 2020 (actual)
- Results
- Posted 10 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will investigate colon pathology in patients with HER2-positive breast cancer treated with neratinib. Colonoscopy will be performed after eligibility has been confirmed, prior to administration of the first dose of neratinib, and after 28 days of neratinib treatment.
Detailed description
This is an open-label, phase 2 study that will investigate colon pathology in patients with HER2-positive breast cancer treated with neratinib as monotherapy.
All patients will receive neratinib for the first 28 days as a single daily dose of 240 mg.
Colonoscopy will be performed after eligibility has been confirmed, but prior to administration of the first dose of neratinib and at Day 30 (± 3 days) the conclusion of Cycle 1 (28 days).
Following the second study colonoscopy procedure:
- 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.
- 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 240 mg daily, until disease progression, death, unacceptable toxicity, or other specified withdrawal criterion.
All patients will receive loperamide diarrhea prophylaxis daily for one 28-day cycle and then as needed.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neratinib | Experimental | Drug: Neratinib, Drug: Capecitabine, Drug: LoperamideNeratinib with loperamide prophylaxis, and capecitabine for participants treated for metastatic breast cancer |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Aged ≥18 years.
- Histologically confirmed stage 1 through stage 4 primary adenocarcinoma of the breast.
- Documented HER2 overexpression or gene-amplified tumor by a validated approved method.
- Participants with confirmed stage 1 to stage 3c breast cancer receiving extended adjuvant treatment with neratinib monotherapy must have completed a course of prior adjuvant trastuzumab or experienced side effects that resulted in early discontinuation of trastuzumab that have since resolved.
- Participants with mBC must have had at least 2 prior HER2-directed regimens.
Key exclusion criteria (17 listed)
- Participants with confirmed stage 1 to stage 3c currently receiving chemotherapy, radiation therapy, immunotherapy, or biotherapy for breast cancer.
- Participants with mBC who have received prior capecitabine or HER2 directed tyrosine kinase inhibitor (TKI) therapy.
- Currently using drugs that have been implicated as causing microscopic colitis/watery diarrhea, such as acarbose, aspirin, proton pump inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), histamine H2 receptor antagonists, selective serotonin reuptake inhibitors, and ticlopidine (Pardi, 2017).
- Major surgery within <28 days of starting treatment or received chemotherapy, investigational agents, or other cancer therapy, except hormonal therapy (e.g., tamoxifen, aromatase inhibitors), <14 days prior to the initiation of investigational products.
- Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of ≥2; including individuals who currently use digitalis, beta-blockers, or calcium channel blockers specifically for congestive heart failure), unstable angina, myocardial infarction within 12 months of enrollment, or ventricular arrhythmia.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NeratinibAlso: NerlynxAdministered orally once daily as a single daily dose of 240 mg | Drug | Neratinib |
| CapecitabineAdministered orally twice daily at 750 mg/m^2 for 14 days of each 21 day treatment cycle | Drug | Neratinib |
| LoperamideAdministered orally for prophylaxis for 28 days and then as needed | Drug | Neratinib |
Primary outcome
Changes in Colon Pathology
Time frame: From baseline to second colonoscopy, which is 88 days after start of neratinib treatment.
The primary endpoint is to describe the changes in colon pathology between the baseline colonoscopy and the second colonoscopy.
1 secondary outcome
Incidence and Severity of Diarrhea
Time frame: From baseline to second colonoscopy, which is 88 days after start of neratinib treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39187401Bowen J, Braga S, Zotto VD, Finnie J, DiPrimeo D, Cooke B, Bischof GF, Wong A, Di Palma JA. Preclinical and clinical evaluation through serial colonoscopic evaluation of neratinib-induced diarrhea in HER2-positive breast cancer-A pilot study. Physiol Rep. 2024 Aug;12(16):e70008. doi: 10.14814/phy2.70008.
- Individual participant dataSharing planned: Yes. Puma Biotechnology is committed to sharing clinical trial data and information to help physicians and patients make informed treatment decisions, and to help qualified researchers advance scientific knowledge. In accordance with legal and regulatory requirements, Puma publishes study protocol information and clinical study results on clinical trial registries, including ClinicalTrials.gov and EU Clinical Trials Register. Puma also publishes information about clinical studies in peer-reviewed scientific journals and shares data in scientific meetings. Puma commits to safeguarding confidentiality and patient privacy throughout the clinical trial data and information sharing process. Any patient-level data will be anonymized to protect personally identifiable information. Qualified researchers and study participants may submit requests for other study documentation and clinical trial data to clinicaltrials@pumabiotechnology.com for consideration.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chief Scientific Officer study director
Puma Biotechnology, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Neratinib, Capecitabine and Loperamide in people with HER2 Amplified Breast Cancer, run by Puma Biotechnology, Inc. at 1 site in Portugal.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Colon Pathology (time frame: From baseline to second colonoscopy, which is 88 days after start of neratinib treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04366713, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2023.