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

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.

Study Overview

• Status: Completed
• Conditions: Breast Neoplasms
• Intervention / Treatment: Drug: neratinib

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation Taussig Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • The Sarah Cannon Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neratinib 80 mg	Drug: neratinib; HKI-272
Experimental: Neratinib 240 mg	Drug: neratinib; HKI-272
Experimental: Neratinib 320 mg	Drug: neratinib; HKI-272
Experimental: Neratinib 40 mg	Drug: neratinib; HKI-272
Experimental: Neratinib 120 mg	Drug: neratinib; HKI-272
Experimental: Neratinib 180 mg	Drug: neratinib; HKI-272
Experimental: Neratinib 400 mg	Drug: neratinib; HKI-272
Experimental: Neratinib 320 mg MTD	Drug: neratinib; HKI-272

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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.
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
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.

Collaborators and Investigators

• Sponsor: Puma Biotechnology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2003
• Primary Completion (Actual): January 1, 2007
• Study Completion (Actual): January 1, 2007

Study Registration Dates

• First Submitted: September 2, 2005
• First Submitted That Met QC Criteria: September 2, 2005
• First Posted (Estimate): September 5, 2005

Study Record Updates

• Last Update Posted (Actual): September 17, 2018
• Last Update Submitted That Met QC Criteria: August 17, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Tumors; Neratinib; HKI-272; Nerlynx
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 3144A1-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No