Study Evaluating HKI-272 in Tumors
- Registration Number
- NCT00146172
- Lead Sponsor
- Puma Biotechnology, Inc.
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 73
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Neratinib 40 mg neratinib - Neratinib 80 mg neratinib - Neratinib 120 mg neratinib - Neratinib 180 mg neratinib - Neratinib 320 mg MTD neratinib - Neratinib 240 mg neratinib - Neratinib 400 mg neratinib - Neratinib 320 mg neratinib -
- Primary Outcome Measures
Name Time Method Dose Limiting Toxicity (DLT) From first dose date to day 14 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.
Maximum Tolerated Dose (MTD) From first dose date to day 14 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.
- Secondary Outcome Measures
Name Time Method Duration of Response From start date of response to first PD, up to 39 weeks. Duration of response of responders (PR+) by Kaplan-Meier estimate
Number of Participants With Best Overall Response From first dose date to progression or last tumor assessment, up to 39 weeks. 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.
Progression Free Survival From first dose date to progression or death, up to 39 weeks. 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.
Objective Response Rate From first dose date to progression/death or last assessment, up to 39 weeks Patients with PR or higher responses, evaluable population
Clinical Benefit Rate From first dose date to progression/death or last assessment, up to 39 weeks. Patients with PR or higher responses or SD\>=24 weeks, evaluable population
Trial Locations
- Locations (5)
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States
The Cleveland Clinic Foundation Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
The Sarah Cannon Cancer Center
🇺🇸Nashville, Tennessee, United States