All Drugs and Chemicals

Amino Acids

Neratinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

neratinib

Puma

The purpose of this study is to assess the tolerability and safety of HKI-272, and to determine the maximum dose that can safety be given. The secondary purpose of this study is to determine how the body uses and gets rid of HKI-272 and to assess whether HKI-272 is effective for the treatment of advanced solid tumors.

This is a phase 1 open-label sequential-group study of ascending single and multiple oral doses administered to subjects with advanced solid tumors. Each subject will participate in only 1 dose group and will receive a single dose of test article, followed by a 1-week observation period, and then will receive the test article administered once-daily by mouth in cycles consisting of 28 days. Subjects will be enrolled in groups of 3 to 6. Adverse events and dose-limiting toxicities will be assessed from the first single dose.

This was an open-label, phase 1, ascending single and multiple oral dose study of neratinib administered to subjects with advanced solid tumors. Each subject participated in only 1 dose group and received a single dose of neratinib. This was followed by a 1-week observation period, and the subject then received neratinib administered as a continual oral daily dose for up to 6 months (6 cycles). Daily dose administration could continue beyond 6 cycles at the same dose level after consultation with the sponsor if neratinib was well tolerated and there was no evidence of progressive disease.

A Study Of The Safety And Tolerability Of HKI-272 Administered Orally To Japanese Subjects With Advanced Solid Tumors

An Ascending and Multiple Dose Study of the Safety, Tolerability, and Pharmacokinetics of HKI-272 Administered Orally to Japanese Subjects With Advanced Solid Tumors

DLT was defined as any drug-related nonhematologic grade 3 or any grade 4 adverse event (AE) according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, except the grade 3 nausea, vomiting, diarrhea, or rash, unless the subject was receiving appropriate medical therapy. Additional DLTs included the following: grade 2 or 3 diarrhea lasting 2 or more days for which the subject was receiving medical therapy or that was associated with fever or dehydration.

MTD is defined as the prior dose level of the dose level which has \>=2 of 3 to 6 subjects that experience a neratinib-related DLT during 21 days from first dose date. A DLT is defined as any HKI-272-related nonhematologic grade 3 or any grade 4 AE according to the Common Terminology Criteria for Adverse Events version 3.0 except: Grade 3 nausea, vomiting, diarrhea, or rash unless subject was receiving appropriate medical therapy.

ORR is defined as the proportion of subjects who had either a complete response (CR) or partial response (PR), according to a modified Response Evaluation Criteria in Solid Tumors (RECIST). The modified RECIST is defined as CR: Disappearance of all target lesions, PR: At least a 30% decrease in the sum of the Longest Diameters (LDs) of target lesions, taking as reference the baseline sum LDs. Response required confirmation.

Subjects with confirmed Complete Response (CR) or confirmed Partial Response (PR), or Stable Disease (SD) \>= 24 weeks, according to a modified Response Evaluation Criteria in Solid Tumors (RECIST). SD is defined as SD in target lesions and a non-progressive disease (PD) in nontarget lesions; A PR is defined as either a PR in target lesions and a non-PD in nontarget lesions, or a CR in target lesions and an incomplete response or SD in nontarget lesions; and a CR is defined as a CR in target lesions and a CR in nontarget lesions.

Puma Biotechnology, Inc.

Neratinib 80 mg

Neratinib 160 mg

Neratinib 240 mg

Neratinib 320 mg

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Japanese

Race/Ethnicity, Customized

Senior Director, Clinical Operations

All subjects who received at least one dose.

Dose Limiting Toxicity (DLT)

Subjects who received at least 14 days of continual dose administration of drug and who had undergone at least 1 follow-up tumor assessment were considered evaluable for efficacy

Spots Global Cancer Trial Database for A Study Of The Safety And Tolerability Of HKI-272 Administered Orally To Japanese Subjects With Advanced Solid Tumors

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