Clinical trial NCT00397046: A Study Of The Safety And Tolerability Of HKI-272 Administered Orally To Japanese Subjects With Advanced Solid Tumors
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Tumors
Keywords: Advanced Malignant Solid Tumors
HKI-272
Neratinib
Nerlynx
Lead sponsor: Puma Biotechnology, Inc.
Sponsor class: INDUSTRY
First posted: 2006-11-08
Enrollment: 21
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion criteria

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

Exclusion Criteria

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

Primary outcomes:
measure: Dose Limiting Toxicity (DLT)
timeFrame: First dose date through 21 days
measure: Maximum Tolerated Dose (MTD)
timeFrame: First dose date through 21 days
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From first dose date to disease progression or last tumor assessment, up to 9.2 months
measure: Clinical Benefit Rate
timeFrame: From first dose date to progression/death or last assessment, up to 9.2 months.
Other outcomes:
Locations:
city: Koto
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation for Cancer Research
state: Tokyo
city: Shizuoka
country: Japan
facility: Shizuoka Cancer Center
Study officials:
affiliation: Biotechnology
name: Puma
role: STUDY_DIRECTOR
References:
citation: Ito Y, Suenaga M, Hatake K, Takahashi S, Yokoyama M, Onozawa Y, Yamazaki K, Hironaka S, Hashigami K, Hasegawa H, Takenaka N, Boku N. Safety, efficacy and pharmacokinetics of neratinib (HKI-272) in Japanese patients with advanced solid tumors: a Phase 1 dose-escalation study. Jpn J Clin Oncol. 2012 Apr;42(4):278-86. doi: 10.1093/jjco/hys012. Epub 2012 Feb 27.