Clinical Trials /

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

NCT03377387

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Capecitabine 7/7 Schedule With Neratinib in Patients With Metastatic HER2-Positive Breast Cancer
  • Official Title: Phase Ib/II Study of Capecitabine 7/7 Schedule With Neratinib in Patients With Metastatic HER2-Positive Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 17-585
  • NCT ID: NCT03377387

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
capecitabinecapecitabine 7/7 with neratinib
neratinibcapecitabine 7/7 with neratinib

Purpose

This is a phase I 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.

Trial Arms

NameTypeDescriptionInterventions
capecitabine 7/7 with neratinibExperimentalIn 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).
  • capecitabine
  • neratinib

Eligibility Criteria

        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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD)
Time Frame:1 year
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Capecitabine
  • Neratinib
  • HER2-Positive
  • 17-585

Last Updated

May 2, 2018