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A Phase 1, Open-Label Study Of Neratinib (HKI-272) In Combination With Capecitabine In Japanese Subject With Solid Tumors

Phase 1
20 Years
Not Enrolling
Advanced Malignant Solid Tumors

Thank you

Trial Information

A Phase 1, Open-Label Study Of Neratinib (HKI-272) In Combination With Capecitabine In Japanese Subject With Solid Tumors

Inclusion Criteria:

- Male and female subjects 20 years and older

- Confirmed pathologic diagnosis of a solid tumor not curable with currently available
therapies, for which neratinib plus capecitabine is a reasonable treatment option.

- At least 1 measurable lesion as defined by Response Evaluation Criteria in Solid
Tumors (RECIST) criteria (Please note: ascites, pleural or pericardial effusion,
osteoblastic bone metastases, and carcinomatous lymphangitis of the lung will not be
considered measurable lesions).

- Subjects with skin lesions that are measurable by computed tomography (CT) scans or
magnetic resonance imaging (MRI) as the only site of measurable disease are allowed.

- Recovery from all clinically significant adverse events (AEs) related to prior
therapies (excluding alopecia).

- Left ventricular ejection fraction (LVEF) within institutional range of normal as
measured by multi-gated acquisition (MUGA) or echocardiogram (ECHO).

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (not declining
within 2 weeks before signing the informed consent form [ICF]).

Screening lab values within the following parameters: Absolute neutrophil count (ANC):
1.5×109/L (1500/mm3) Platelet count: 100×109/L (100,000/mm3) Hemoglobin: 9.0 g/dL (90 g/L)
Serum creatinine: 01.5×upper limit of normal (ULN) Total bilirubin: 1.5×ULN (<3 ULN if
Gilbert's disease) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT):
2.5×ULN (=5×ULN if liver metastases are present)

- For women of childbearing potential, a negative urine or serum pregnancy test result
before study entry.

- All subjects who are biologically capable of having children must agree and commit to
the use of a reliable method of birth control for the duration of the study and for
28 days after the last dose of investigational product. A subject is biologically
capable of having children if he or she is using contraceptives or if his or her
sexual partner is sterile or using contraceptives.

Exclusion Criteria:

- Prior treatment with anthracyclines with a cumulative dose of doxorubicin >400 mg/m²,
or of epirubicin >800 mg/m², or the equivalent dose for other anthracyclines or

- Major surgery, chemotherapy, radiotherapy, any investigational agents, or other
cancer therapy within at least 2 weeks before administration of the first dose of
investigational product.

- Bone as the ONLY site of disease .

- Active central nervous system (CNS) metastases, as indicated by clinical symptoms,
cerebral edema, and/or progressive growth (subjects with a history of CNS metastases
or cord compression are permitted if they have been definitively treated and are off
anticonvulsants and steroids for at least 4 weeks before cycle 1 day 1).

QT (corrected QT (QTc)) interval >0.47seconds or a known history of QTc prolongation or
torsades de pointes.

- Presence of clinically significant or uncontrolled cardiac disease, including
congestive heart failure (New York Heart Association [NYHA] functional classification
of 02), angina requiring treatment, myocardial infarction within the past 12 months,
or any clinically significant supraventricular arrhythmia or ventricular arrhythmia
requiring treatment or intervention.

- Pregnant or breastfeeding women.

- Significant chronic or recent acute gastrointestinal disorder with diarrhea as a
major symptom (eg, Crohn's disease, malabsorption, or grade 2 or higher diarrhea of
any etiology at baseline).

- Inability or unwillingness to swallow tablets (neratinib and capecitabine).

- Subjects with active or uncontrolled renal insufficiency, in whom medication dose
adjustments are indicated.

- Subject known to be human immunodeficiency virus (HIV) seropositive and/or have acute
or chronic hepatitis B infection (hepatitis B surface antigen [HBsAg] positive) or
hepatitis C infection (anti-HCV positive).

- Known history of hypersensitivity to capecitabine or any of it components, including

- Any other cancer within 5 years prior to screening with the exception of
contralateral breast carcinoma, adequately treated cervical carcinoma in situ, or
adequately treated basal or squamous cell carcinoma of the skin.

- Clinically significant ongoing or recent infection within 2 weeks before
administration of the first dose of investigational product.

- Evidence of significant medical illness or abnormal laboratory findings that in the
investigator's judgment will substantially increase the risk associated with the
subject's participation in and completion of the study, or preclude the evaluation of
the subject's response. Examples include, but are not limited to, serious active
infection, (ie, requiring intravenous antibiotic or antiviral agent) or uncontrolled
major seizure disorder, significant pulmonary disorder (eg, interstitial pneumonitis,
pulmonary hypertension), or psychiatric disorder that would interfere with subject
safety or informed consent.

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The primary objectives are to assess the safety and tolerability of neratinib in combination with capecitabine in Japanese subjects with advanced solid tumors, and to confirm the recommended dose of the regimen.

Outcome Time Frame:

12 months

Safety Issue:


Principal Investigator


Investigator Role:

Study Director

Investigator Affiliation:



Japan: Ministry of Health, Labor and Welfare

Study ID:




Start Date:

April 2010

Completion Date:

March 2011

Related Keywords:

  • Advanced Malignant Solid Tumors
  • Neratinib
  • Capecitabine
  • Combination
  • Solid Tumor
  • Neoplasms