Title
Study Evaluating HKI-272 in Tumors
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
Phase
Phase 1Lead Sponsor
Puma Biotechnology, Inc.Study Type
InterventionalStatus
Completed Results PostedIndication/Condition
Breast NeoplasmsIntervention/Treatment
nerlynx ...Study Participants
73The 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.
HKI-272
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
| Event Type | Organ System | Event Term | Neratinib 40 mg | Neratinib 80 mg | Neratinib 120 mg | Neratinib 180 mg | Neratinib 240 mg | Neratinib 320 mg | Neratinib 400 mg | Neratinib 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.
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.
Duration of response of responders (PR+) by Kaplan-Meier estimate
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.
Patients with PR or higher responses, evaluable population
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.
Patients with PR or higher responses or SD>=24 weeks, evaluable population
