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

Phase 1

Completed

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
Dose Limiting Toxicity (DLT)	First dose date through 21 days	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.
Maximum Tolerated Dose (MTD)	First dose date through 21 days	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.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	From first dose date to disease progression or last tumor assessment, up to 9.2 months	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.
Clinical Benefit Rate	From first dose date to progression/death or last assessment, up to 9.2 months.	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.

Locations (2): Shizuoka Cancer Center
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Shizuoka, Japan
The Cancer Institute Hospital of Japanese Foundation for Cancer Research
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Koto, Tokyo, Japan