Study Evaluating HKI-272 in Tumors

Breast Neoplasms Clinical Trial

Official title:

An Ascending Single and Multiple Dose Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HKI-272 Administered Orally to Subjects With HER-2/NEU or HER-1/EGFR-Positive Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00146172
• Other study ID #: 3144A1-102
• Status: Completed
• Phase: Phase 1
• Start date: November 2003
• Est. completion date: January 2007

Study information

• Verified date: August 2018
• Source: Puma Biotechnology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and tolerability as well as find the maximum tolerated dose (MTD) for HKI-272. In addition, this study will examine the effects of the study drug on your tumor, and how your body uses and eliminates HKI-272.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: January 2007
• Est. primary completion date: January 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Her2/neu or Her1/EGFR positive cancer

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

• Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)

Exclusion Criteria:

• Prior treatment with anthracyclines with a cumulative dose of doxorubicin or equivalent of greater than 300 mg/m^2

• Patients with significant cardiac risk factors

• Active central nervous system metastasis

Related Conditions & MeSH terms

• Breast Neoplasms

Intervention

Drug:
• neratinib
HKI-272

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	The Cleveland Clinic Foundation Taussig Cancer Center	Cleveland	Ohio
United States	The Sarah Cannon Cancer Center	Nashville	Tennessee
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Puma Biotechnology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicity (DLT)	DLT is defined as any neratinib-related nonhematologic grade 3 or any grade 4 adverse event (AE) according to the National Cancer Institute (NCI) common terminology criteria (CTC) for AEs version 3.0. DLTs were assessed from the first single dose to 14 days of continuous daily administration.	From first dose date to day 14
Primary	Maximum Tolerated Dose (MTD)	If 2 or more, of 3 to 6 subjects, at a dose level had an neratinib-related dose limiting toxicity (DLT) by day 14 of continuous daily dose administration, dose escalation stopped and the prior dose level was considered the MTD.	From first dose date to day 14
Secondary	Number of Participants With Best Overall Response	Best Overall response by tumor type, evaluable population per Response Evaluation Criteria In Solid Tumors Criteria v1.0 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in sum of the longest diameter (LD) of target lesions in reference to baseline sum of LD of target lesions; Progressive Disease (PD), >=20% increase in sum of LD of target lesions, taking as reference the smallest sum of recorded LD of target lesions since treatment started or appearance of 1 or more new lesions; Stable disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of LD of target lesions since the treatment start. The best overall response was the best response recorded from start of treatment until PD/recurrence. In general, the subject's best response assignment depended on achievement of both measurement and confirmation criteria.	From first dose date to progression or last tumor assessment, up to 39 weeks.
Secondary	Duration of Response	Duration of response of responders (PR+) by Kaplan-Meier estimate	From start date of response to first PD, up to 39 weeks.
Secondary	Progression Free Survival	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	From first dose date to progression or death, up to 39 weeks.
Secondary	Objective Response Rate	Patients with PR or higher responses, evaluable population	From first dose date to progression/death or last assessment, up to 39 weeks
Secondary	Clinical Benefit Rate	Patients with PR or higher responses or SD>=24 weeks, evaluable population	From first dose date to progression/death or last assessment, up to 39 weeks.