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

DLT was defined as 1. Grade 3 or 4 non-hematologic toxicity (exceptions listed below as a.-c.), a. Grade 3 asthenia was NOT considered to be a DLT UNLESS it lasted \>3 days. b. Grade 3 nausea or vomiting was NOT considered to be a DLT UNLESS the subject was already receiving optimal medical therapy. c. Grade 3 or 4 infection was NOT considered to be a DLT UNLESS it is associated with grade 3 or 4 neutropenia. 2. Grade 3 diarrhea that lasted \>2 days while the subject was on optimal medical therapy or that was associated with fever (greater than or equal 38.0 ºC) or grade 3 dehydration. 3. Grade 4 neutropenia lasting ≥3 days or grade 4 febrile neutropenia. 4. Grade 4 thrombocytopenia lasting ≥3 days or complicated with bleeding or requiring platelet transfusion. 5. Delayed recovery (to National Cancer Institute \[NCI\] grade 1 or less, or baseline) from any of the toxicities listed above (items 1-4), that was related to study drug, and that delayed the next dose by more than 3 weeks.

Time frame: From first dose date to day 21.

Population: The safety population was defined as all subjects who received at least 1 dose of investigational product (neratinib and/or capecitabine).

Six subjects will be initially enrolled (neratinib 240 mg/day; capecitabine 1500 mg/m²/day on days 1 through 14). AEs and DLTs will be assessed from the first dose of investigational product through day 21. Based on the DLT rate in these first 6 subjects, dose tolerability will be confirmed as follows: If ≤1 of the first 6 evaluable subjects experience a DLT by day 21, then this dose is considered tolerable, and enrollment will stop. If ≥3 of the first 6 evaluable subjects experience a DLT by day 21, this dose is considered intolerable. If 2 of the first 6 evaluable subjects experience a DLT by day 21, then an additional 4 subjects will be enrolled at the same dose level. If a total of 10 subjects are enrolled, then the tolerability will be confirmed as follows: If ≤3 of the total 10 subjects experience a DLT by day 21, then this dose will be considered tolerable. If ≥4 of the total 10 subjects experience a DLT by day 21, then the dose will be considered intolerable.

Time frame: From first dose date to day 21.

Population: The safety population was defined as all subjects who received at least 1 dose of investigational product (neratinib and/or capecitabine).

AUC of Neratinib at day 14 following Administration of Neratinib 240 mg in combination with Capecitabine 1500 mg/m\^2 per day to Japanese Subjects with Cancer.

Time frame: At 1, 2, 4, 6, 8 and 21-24 hours after dose on day 14.

Population: The pharmacokinetic population was defined as all subjects who received at least 1 dose of investigational product (neratinib and/or capecitabine).

Number of participants with Partial Response (PR) or Complete Response (CR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) (v1.0) criteria. CR: Disappearance of all lesions; PR: at least a 30% decrease in the sum of longest diameters (SLD) of target lesions, taking as reference the baseline SLD; Progressive Disease (PD): at least a 20% increase in the SLD of target lesions, taking as reference the nadir longest diameter, meaning the smallest SLDs recorded since the treatment started, or the appearance of 1 or more new lesions, or unequivocal progression of existing nontarget lesions; and stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD since treatment started.

Time frame: From first dose date to progression or last tumor assessment, up to 41 weeks.

Population: All subjects who met Inclusion and Exclusion criteria, received at least 2 weeks of Investigational Product, and underwent at least 1 Follow Up (FU) tumor assessment at approximately cycle 2 (week 6). Subjects who died or had PD including symptomatic deterioration before the scheduled FU tumor assessment were included in the evaluable population.

Maximum plasma concentration (nanograms/milliliter) of Neratinib at day 14 following Administration of Neratinib 240 mg in combination with Capecitabine 1500 mg/m\^2 per day to Japanese Subjects with Cancer.

Time frame: Measured at 1, 2, 4, 6, 8 and 21-24 hours after dose on day 14.

Population: The pharmacokinetic population was defined as all subjects who received at least 1 dose of investigational product (neratinib and/or capecitabine).

Percentage of participants with partial response (PR) or complete response (CR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: CR, disappearance of all target lesions; PR, \>=30% decrease in the sum of the longest diameter of target lesions; and Non Progressive Disease (PD) for non-target lesions, and no new lesions.

Time frame: From first dose date to progression or last tumor assessment, up to 41 weeks.

Population: All subjects who met Inclusion and Exclusion criteria, received at least 2 weeks of Investigational Product, and underwent at least 1 Follow Up (FU) tumor assessment at approximately cycle 2 (week 6). Subjects who died or had PD including symptomatic deterioration before the scheduled FU tumor assessment were included in the evaluable population.

Number of weeks between the date of the first dose of test article and the first date of disease recurrence or disease progression (PD), or death due to any cause, was documented, censored at the last evaluation, investigator assessment. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (v1.0), as at least a 20% increase in the sum of the longest diameters (LD) of target lesions, taking as reference the nadir LD, meaning the smallest sum of the LDs recorded since the treatment started; or unequivocal progression of existing nontarget lesions; or the appearance of any new lesions.

Time frame: From first dose date to PD or death, up to 41 weeks.

Population: All subjects who met Inclusion and Exclusion criteria, received at least 2 weeks of Investigational Product, and underwent at least 1 Follow Up (FU) tumor assessment at approximately cycle 2 (week 6). Subjects who died or had PD including symptomatic deterioration before the scheduled FU tumor assessment were included in the evaluable population.