Breast CancerPhase 1/2NCT03377387
Capecitabine 7/7 Schedule With Neratinib in Patients With Metastatic HER2-Positive Breast Cancer
A Phase 1/2 study testing Capecitabine, Neratinib and EORTC QLQ - BR23, EQ-5D-5L, EORTC QLQ-C30 in people with Breast Cancer, run by Memorial Sloan Kettering Cancer Center at 10 sites in United States.
Trial summary
This is a phase l/II study. The purpose of this study is to test the safety of the study drug neratinib in combination with a standard chemotherapy drug called capecitabine at different doses to find out what effects, if any, it has on people. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Capecitabine, Neratinib and EORTC QLQ - BR23, EQ-5D-5L, EORTC QLQ-C30
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 10 sitesUnited States
- Study dates
- 13 Dec 2017to 14 Oct 2026
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged ≥18 years at signing of informed consent.
- Histologically confirmed MBC, current stage IV.
- Documented HER2 overexpression (immunohistochemistry (IHC) 3+ or gene-amplified tumor with fluorescence in situ hybridization (FISH) ratio of ≥ 2.0.
- For phase Ib, any line of prior treatments is permitted including prior neratinib and capecitabine.
- For phase II, up to 4 prior chemotherapy-based treatments in the metastatic setting are allowed. Patients must have had prior trastuzumab-based therapy. Prior neratinib treatment is not permitted. Prior capecitabine is allowed, if not combined with neratinib.
- Measurable or non-measurable disease is permitted as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) for phase 1b. For phase 2, patients must have measurable disease as defined in RECIST v1.1.
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- Left ventricular ejection fraction (LVEF) ≥50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).
- Eastern Cooperative Oncology Group (ECOG) status of 0 to 1
- Hematologic parameters: white blood cell (WBC) count of > 3000/ul, absolute neutrophil count (ANC) ≥ 1000/ul, platelets ≥ 50,000/ul, hemoglobin ≥ 8.0 g/dl
- Non-hematologic parameters: bilirubin ≤ 1.5 mg/dl, AST/ALT ≤ 3.0 x upper limit of normal (ULN) (≤ 5.0 x ULN if liver metastases are involved)
- Creatinine ≤1.5 mg/dl Patients with "treated and stable" brain lesions of a duration of ≥ 2 months may be enrolled.
- 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 of childbearing potential must agree and commit to the use of a highly effective method of contraception as determined to be acceptable by the investigator, from the time of informed consent until 28 days after the last dose of the investigational product. Men must agree and commit to use a barrier method of contraception while on treatment and for 3 months after last dose of investigational products.
- Provide written, informed consent to participate in the study and follow the study procedures
Who cannot join
- Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of ≥2), unstable angina, myocardial infarction within 12 months of enrollment, or ventricular arrhythmia
- Received prior therapy resulting in a cumulative epirubicin dose >900 mg/m2 or cumulative doxorubicin dose >450 mg/m2. If another anthracycline or more than one anthracycline has been used, the cumulative dose must not exceed the equivalent of 450 mg/m^2 doxorubicin.
- Any major surgery ≤28 days prior to the initiation of investigational products, or received anti-cancer therapy (including chemotherapy, biological therapy, hormonal therapy, investigational agents, or other anti-cancer therapy) administered ≤14 days prior to the initiation of investigational products.
- Received radiation therapy ≤14 days prior to initiation of investigational products.
- QTc interval >450 ms for men or 470 ms for women, or known history of QTc prolongation or Torsades de Pointes.
- Active hepatitis B or C
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- Active infection or unexplained fever >38.5°C (>101.3°F) within 2 weeks prior to enrollment.
- Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or Grade ≥2 diarrhea of any etiology screening).
- Known dihydropyrimidine dehydrogenase deficiency.
- Known hypersensitivity to 5-fluorouracil or to any component of the investigational products or compounds of similar chemical composition.
- Pregnant patients or currently breast-feeding.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Lehigh Valley Health Network
Allentown, Pennsylvania, 18103
Memorial Sloan Kettering at Basking Ridge
Basking Ridge, New Jersey, 07920
Memorial Sloan Kettering Commack
Commack, New York, 11725
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Hartford Healthcare Cancer Institute @ Hartford Hospital
Hartford, Connecticut, 06102
Baptist Alliance - McI
Miami, Florida, 33143
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553
About this study
Official title: Phase Ib/II Study of Capecitabine 7/7 Schedule With Neratinib in Patients With Metastatic HER2-Positive Breast Cancer
This is a phase l/II study. The purpose of this study is to test the safety of the study drug neratinib in combination with a standard chemotherapy drug called capecitabine at different doses to find out what effects, if any, it has on people. Capecitabine (Xeloda®) is approved by the Food and Drug Administration (FDA) for advanced breast cancer treatment. Neratinib is an investigational drug, meaning the FDA has not approved the use of this drug for advanced breast cancer. The combination of capecitabine and neratinib has been studied before in another study where capecitabine was administered using the standard dosing schedule. In this study, the investigators want to find out if a different dosing schedule of capecitabine combined with neratinib is safer. This different dosing schedule is experimental, meaning the administration schedule of capecitabine and neratinib is not FDA approved for treatment for HER2 positive advanced breast cancer.
- Conditions
- Breast Cancer
- Being tested
- Capecitabine, Neratinib, EORTC QLQ - BR23, EQ-5D-5L, EORTC QLQ-C30
- Keywords
- Capecitabine, Neratinib, HER2-Positive, 17-585
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapecitabineDrug
Capecitabine will be taken orally in AM and PM (at the assigned dose per cohort) 7 days on and 7 days off. Phase II MD 1000mg BID of capecitabine.
NeratinibDrug
Neratinib is given as 240 mg daily continuously without stopping. A cycle is 28 days. Phase II The MD has been determined as 240mg of neratinib
EORTC QLQ - BR23, EQ-5D-5L, EORTC QLQ-C30Behavioural
Questionnaires Every Cycle (+/- 3 days) (For phase II)
| Study group | Role | What they receive |
|---|---|---|
| capecitabine 7/7 with neratinib | Experimental | In the phase I portion of the study, a 3+3 design will be used. Once the MTD is reached, the phase II portion will enroll up to 24 patients. Capecitabine will be taken orally in AM and PM (at the assigned dose per cohort) 7 days on and 7 days off. Neratinib is given as 240 mg daily continuously without stopping. A cycle is 28 days. Patients will be seen on Day 1 of each cycle (+/- 3 days).
The MD has been determined as 240mg of neratinib and 1000mg BID of capecitabine. Receives: Drug: Capecitabine; Drug: Neratinib; Behavioral: EORTC QLQ - BR23, EQ-5D-5L, EORTC QLQ-C30 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD)
If 0 of the 3 patients entered at a dose level experiences a DLT, another 3 patients will be treated at the next higher dose level. If 1 of 3 patients in a cohort experiences a DLT, then up to 3 additional patients will be treated at the same dose level. If none of these 3 additional patients experience a DLT, then the dose will be escalated to the next higher dose level. If > 2 of the initial 3 or 6 patients at a dose level experience a DLT, then the MTD will have been exceeded, and de-escalation is warranted. De-escalation will continue if > 2 of the initial 3 or 6 patients in a dose level cohort experience a DLT. There will be 2 dose de-escalation levels (dose levels -1 and -2) and one dose escalation (dose level +1) as shown in the table below. If < 1 of 6 patients, at that dose level, experience a DLT, then that dose level will be confirmed as the MTD.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2017
- Study start13 Dec 2017
- Primary completion14 Oct 2026
- Study completion14 Oct 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a phase Ib/II study of capecitabine 7/7 with neratinib in patients with HER2-positive metastatic breast cancer.
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Puma Biotechnology, Inc.
- Responsible party
- Sponsor
- Investigators
- Chau Dang, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03377387
- Sponsor's protocol ID
- 17-585
- Status last verified
- Oct 2026
- First submitted
- 14 Dec 2017
- Last updated
- 16 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib/II Study of Capecitabine 7/7 Schedule With Neratinib in Patients With Metastatic HER2-Positive Breast Cancer
- ClinicalTrials.gov ID
- NCT03377387
- Acronym / sponsor ID
- 17-585
- Conditions
- Breast Cancer
- Keywords
- Capecitabine, Neratinib, HER2-Positive, 17-585
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Puma Biotechnology, Inc.
- Study start
- 13 Dec 2017 (actual)
- Primary completion
- 14 Oct 2026 (actual)
- Study completion
- 14 Oct 2026 (actual)
- First posted
- 19 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase l/II study. The purpose of this study is to test the safety of the study drug neratinib in combination with a standard chemotherapy drug called capecitabine at different doses to find out what effects, if any, it has on people. Capecitabine (Xeloda®) is approved by the Food and Drug Administration (FDA) for advanced breast cancer treatment. Neratinib is an investigational drug, meaning the FDA has not approved the use of this drug for advanced breast cancer. The combination of capecitabine and neratinib has been studied before in another study where capecitabine was administered using the standard dosing schedule. In this study, the investigators want to find out if a different dosing schedule of capecitabine combined with neratinib is safer. This different dosing schedule is experimental, meaning the administration schedule of capecitabine and neratinib is not FDA approved for treatment for HER2 positive advanced breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a phase Ib/II study of capecitabine 7/7 with neratinib in patients with HER2-positive metastatic breast cancer.
| Arm | Type | Receives |
|---|---|---|
| capecitabine 7/7 with neratinib | Experimental | Drug: Capecitabine, Drug: Neratinib, Behavioral: EORTC QLQ - BR23, EQ-5D-5L, EORTC QLQ-C30In the phase I portion of the study, a 3+3 design will be used. Once the MTD is reached, the phase II portion will enroll up to 24 patients. Capecitabine will be taken orally in AM and PM (at the assigned dose per cohort) 7 days on and 7 days off. Neratinib is given as 240 mg daily continuously without stopping. A cycle is 28 days. Patients will be seen on Day 1 of each cycle (+/- 3 days). The MD has been determined as 240mg of neratinib and 1000mg BID of capecitabine. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Aged ≥18 years at signing of informed consent.
- Histologically confirmed MBC, current stage IV.
- Documented HER2 overexpression (immunohistochemistry (IHC) 3+ or gene-amplified tumor with fluorescence in situ hybridization (FISH) ratio of ≥ 2.0.
- For phase Ib, any line of prior treatments is permitted including prior neratinib and capecitabine.
- For phase II, up to 4 prior chemotherapy-based treatments in the metastatic setting are allowed. Patients must have had prior trastuzumab-based therapy. Prior neratinib treatment is not permitted. Prior capecitabine is allowed, if not combined with neratinib.
Key exclusion criteria (11 listed)
- Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of ≥2), unstable angina, myocardial infarction within 12 months of enrollment, or ventricular arrhythmia
- Received prior therapy resulting in a cumulative epirubicin dose >900 mg/m2 or cumulative doxorubicin dose >450 mg/m2. If another anthracycline or more than one anthracycline has been used, the cumulative dose must not exceed the equivalent of 450 mg/m^2 doxorubicin.
- Any major surgery ≤28 days prior to the initiation of investigational products, or received anti-cancer therapy (including chemotherapy, biological therapy, hormonal therapy, investigational agents, or other anti-cancer therapy) administered ≤14 days prior to the initiation of investigational products.
- Received radiation therapy ≤14 days prior to initiation of investigational products.
- QTc interval >450 ms for men or 470 ms for women, or known history of QTc prolongation or Torsades de Pointes.
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 |
|---|---|---|
| CapecitabineCapecitabine will be taken orally in AM and PM (at the assigned dose per cohort) 7 days on and 7 days off. Phase II MD 1000mg BID of capecitabine. | Drug | capecitabine 7/7 with neratinib |
| NeratinibNeratinib is given as 240 mg daily continuously without stopping. A cycle is 28 days. Phase II The MD has been determined as 240mg of neratinib | Drug | capecitabine 7/7 with neratinib |
| EORTC QLQ - BR23, EQ-5D-5L, EORTC QLQ-C30Questionnaires Every Cycle (+/- 3 days) (For phase II) | Behavioural | capecitabine 7/7 with neratinib |
Primary outcome
Maximum Tolerated Dose (MTD)
Time frame: 1 year
If 0 of the 3 patients entered at a dose level experiences a DLT, another 3 patients will be treated at the next higher dose level. If 1 of 3 patients in a cohort experiences a DLT, then up to 3 additional patients will be treated at the same dose level. If none of these 3 additional patients experience a DLT, then the dose will be escalated to the next higher dose level. If > 2 of the initial 3 or 6 patients at a dose level experience a DLT, then the MTD will have been exceeded, and de-escalation is warranted. De-escalation will continue if > 2 of the initial 3 or 6 patients in a dose level cohort experience a DLT. There will be 2 dose de-escalation levels (dose levels -1 and -2) and one dose escalation (dose level +1) as shown in the table below. If < 1 of 6 patients, at that dose level, experience a DLT, then that dose level will be confirmed as the MTD.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2026.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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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.
Chau Dang, MD principal investigator
Memorial Sloan Kettering Cancer Center
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Capecitabine, Neratinib and EORTC QLQ - BR23, EQ-5D-5L, EORTC QLQ-C30 in people with Breast Cancer, run by Memorial Sloan Kettering Cancer Center at 10 sites in United States.
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 14 inclusion and 11 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 16 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Maximum Tolerated Dose (MTD) (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Oct 2026.