Clinical trial NCT01128842: A Study Of Neratinib (HKI-272) And Capecitabine In Japanese With Solid Tumor
Official title: A Phase 1, Open-Label Study Of Neratinib (HKI-272) In Combination With Capecitabine In Japanese Subject With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Malignant Solid Tumors
Keywords: Neratinib
Capecitabine
Combination
Solid Tumor
Lead sponsor: Puma Biotechnology, Inc.
Sponsor class: INDUSTRY
First posted: 2010-05-24
Enrollment: 7
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Dose Limiting Toxicity (DLT) - Percentage of Participants With DLT Events
timeFrame: From first dose date to day 21.
measure: Tolerated Dose
timeFrame: From first dose date to day 21.
Secondary outcomes:
measure: Best Overall Response
timeFrame: From first dose date to progression or last tumor assessment, up to 41 weeks.
measure: Objective Response Rate
timeFrame: From first dose date to progression or last tumor assessment, up to 41 weeks.
measure: Progression Free Survival
timeFrame: From first dose date to PD or death, up to 41 weeks.
measure: Area Under the Curve (AUC) of Neratinib in Combination With Capecitabine
timeFrame: At 1, 2, 4, 6, 8 and 21-24 hours after dose on day 14.
measure: Maximum Plasma Concentration of Neratinib in Combination With Capecitabine
timeFrame: Measured at 1, 2, 4, 6, 8 and 21-24 hours after dose on day 14.
Other outcomes:
Locations:
city: Shizuoka
country: Japan
facility: Investigational Site
city: Tokyo
country: Japan
facility: Investigational Site
Study officials:
affiliation: Biotechnology
name: Puma
role: STUDY_DIRECTOR
References: