Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Amino Acids

Neratinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

neratinib

Puma

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.

This trial was an open-label, phase 1, ascending single and multiple oral dose study of HKI-272 administered to subjects with erbB-2- or erbB-1-positive tumors. Each subject participated in only 1 dose group and received a single dose of test article, followed by a 1-week observation period, and then received the test article administered once daily by mouth for up to 6 months (6 cycles). Daily dose administration could continue beyond 6 cycles at the same dose level if HKI-272 was well tolerated and there was no evidence of progressive disease.

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

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.

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.

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.

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

Patients with PR or higher responses or SD\>=24 weeks, evaluable population

Puma Biotechnology, Inc.

Neratinib 40 mg

Neratinib 80 mg

Neratinib 120 mg

Neratinib 180 mg

Neratinib 240 mg

Neratinib 320 mg

Neratinib 400 mg

Neratinib maximum tolerated dose (320 mg).

Neratinib MTD

Neratinib maximum tolerated dose (320 mg) from part 2.

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Senior Director, Clinical Operations

Subjects in the dosing groups 40 mg through 400 mg, excluding the selection of MTD.

Dose Limiting Toxicity (DLT)

Partial Response

Stable Disease >=24 weeks

Stable Disease >=16 weeks

Stable Disease >=8 weeks

Progressive Disease

Breast Cancer Cohort

Lung Cancer Cohort

All Subjects

Subjects who had received at least 14 days of continuous dose administration of test article and who had undergone at least 1 follow-up tumor assessment, evaluable population

Number of Participants With Best Overall Response

Breast Cancer

Lung Cancer

Subjects responses classified as complete response or partial response in evaluable population

Duration of Response

All subjects who were assigned to treatment, received at least 14 days of continuous dose administration of test article, and who had undergone at least 1 follow-up tumor assessment, evaluable population

Progression Free Survival

Subjects with breast cancer in all doses of neratinib

Subjects with Lung cancer in all doses of Neratinib

Subjects with solid tumors in all doses of Neratinib

All Solid Tumors

Breast, Lung and other solid tumors included in the efficacy evaluable population

Spots Global Cancer Trial Database for Study Evaluating HKI-272 in Tumors

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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