Capecitabine 7/7 Schedule With Neratinib in Patients With Metastatic HER2-Positive Breast Cancer

April 17, 2023 updated by: Memorial Sloan Kettering Cancer Center

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.

Study Overview

Study Type

Interventional

Enrollment (Actual)

34

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Connecticut
      • Hartford, Connecticut, United States, 06102
        • Hartford Healthcare Cancer Institute @ Hartford Hospital
    • Florida
      • Miami, Florida, United States, 33143
        • Baptist Alliance - McI
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Memorial Sloan Kettering at Basking Ridge
      • Middletown, New Jersey, United States, 07748
        • Memorial Sloan Kettering Monmouth
      • Montvale, New Jersey, United States, 07645
        • Memorial Sloan Kettering Bergen
    • New York
      • Commack, New York, United States, 11725
        • Memorial Sloan Kettering Commack
      • Harrison, New York, United States, 10604
        • Memorial Sloan Kettering Westchester
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • Uniondale, New York, United States, 11553
        • Memorial Sloan Kettering Nassau
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • Lehigh Valley Health Network

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.
  • 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

Exclusion Criteria:

  • 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
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: capecitabine 7/7 with neratinib

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.

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.
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
Questionnaires Every Cycle (+/- 3 days) (For phase II)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: Chau Dang, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 13, 2017

Primary Completion (Anticipated)

December 1, 2024

Study Completion (Anticipated)

December 1, 2024

Study Registration Dates

First Submitted

December 14, 2017

First Submitted That Met QC Criteria

December 14, 2017

First Posted (Actual)

December 19, 2017

Study Record Updates

Last Update Posted (Actual)

April 18, 2023

Last Update Submitted That Met QC Criteria

April 17, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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