A Study Of Neratinib (HKI-272) And Capecitabine In Japanese With Solid Tumor

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01128842
Recruitment Status : Completed
First Posted : May 24, 2010
Last Update Posted : May 14, 2012
Information provided by (Responsible Party):
Puma Biotechnology, Inc.

Brief Summary:
This is an open-label, phase 1 study of ascending single cohort of neratinib (HKI-272) combination with capecitabine.

Condition or disease Intervention/treatment Phase
Advanced Malignant Solid Tumors Drug: Neratinib + Capecitabine Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-Label Study Of Neratinib (HKI-272) In Combination With Capecitabine In Japanese Subject With Solid Tumors
Study Start Date : April 2010
Actual Primary Completion Date : March 2011
Actual Study Completion Date : March 2011

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Neratinib + Capecitabine
Neratinib + Capecitabine
Drug: Neratinib + Capecitabine
Neratinib: 240 mg, continuous daily OD Capecitabine: 1500 mg/m^2, BID

Primary Outcome Measures :
  1. 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. [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. The secondary objectives of this study are to obtain preliminary antitumor activity for neratinib combined with capecitabine and to obtain Pharmacokinetic (PK) information [ Time Frame: 12 months ]

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 derivatives.
  • 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 5-FU.
  • 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.

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01128842

Investigational Site
Shizuoka, Japan
Investigational Site
Tokyo, Japan
Sponsors and Collaborators
Puma Biotechnology, Inc.
Study Director: Puma Biotechnology

Responsible Party: Puma Biotechnology, Inc. Identifier: NCT01128842     History of Changes
Other Study ID Numbers: 3144A1-1122
First Posted: May 24, 2010    Key Record Dates
Last Update Posted: May 14, 2012
Last Verified: May 2012

Keywords provided by Puma Biotechnology, Inc.:
Solid Tumor

Additional relevant MeSH terms:
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents