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NCT Number: NCT00397046

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

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.

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Key information

Conditions

Tumors Neoplasms

Age range

20 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Koto, Tokyo, Japan

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Diagnosis of metastatic or advanced cancer that has failed standard effective therapy
  • Life expectancy of at least 12 weeks and adequate performance status
  • Adequate bone marrow, kidney and liver function
  • Willingness of male and female subjects who are not surgically sterile or post-menopausal to use adequate methods of birth control

Exclusion criteria

  • Any anticancer chemotherapy, radiotherapy immunotherapy or investigational agents within 4 weeks of first dose of HKI-272
  • Inadequate cardiac function
  • Surgery within 2 weeks of first dose of HKI-272
  • Active central nervous system metastases (i.e., symptomatic, required use of corticosteroids and/or progressive growth)
  • Significant gastrointestinal disorder with diarrhea as a major symptom
  • Pregnant or breast feeding women

Treatment and study plan

Neratinib

Drug

HKI-272

Primary outcomes

  1. Dose Limiting Toxicity (DLT)

    Time frame: 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.

  2. Maximum Tolerated Dose (MTD)

    Time frame: 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 outcomes

  1. Objective Response Rate (ORR)

    Time frame: 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.

  2. Clinical Benefit Rate

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Puma Biotechnology, Inc.

Industry

Registry information

Official study title

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

Important dates

Study start
2006
Primary completion
2009
Study completion
2009
First posted
Nov 8, 2006
Registry last updated
Sep 14, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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