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

NCT00397046 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 3144A1-104
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

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.

Conditions

Tumors

Keywords

Advanced Malignant Solid Tumors; HKI-272; Neratinib; Nerlynx

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity (DLT)

  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.

  First dose date through 21 days

• Maximum Tolerated Dose (MTD)

  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.

  First dose date through 21 days

Secondary Outcomes (2)

• Objective Response Rate (ORR)

  From first dose date to disease progression or last tumor assessment, up to 9.2 months

• Clinical Benefit Rate

  From first dose date to progression/death or last assessment, up to 9.2 months.

Study Arms (4)

Neratinib 80 mg

EXPERIMENTAL

Drug: neratinib

Neratinib 160 mg

EXPERIMENTAL

Drug: neratinib

Neratinib 240 mg

EXPERIMENTAL

Drug: neratinib

Neratinib 320 mg

EXPERIMENTAL

Drug: neratinib

Interventions

neratinib DRUG

HKI-272

Neratinib 160 mg; Neratinib 240 mg; Neratinib 320 mg; Neratinib 80 mg

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Puma Biotechnology, Inc.: lead

Study Sites (2)

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Koto, Tokyo, 135-8550, Japan

Location

Shizuoka Cancer Center

Shizuoka, 1411-8777, Japan

Location

Related Publications (1)

• 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.

  PMID: 22371427 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

neratinib

Results Point of Contact

• Title: Senior Director, Clinical Operations
• Organization: Puma Biotechnology, Inc.

clinicaltrials@pumabiotechnology.com

+1 (424) 248-6500

Study Officials

• Puma

  Biotechnology

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 7, 2006
• First Posted: November 8, 2006
• Study Start: November 1, 2006
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: September 14, 2018
• Results First Posted: February 19, 2018

Record last verified: 2018-08

Locations

JP (2)