Study Evaluating HKI-272 in Tumors

• ClinicalTrials.gov Identifier: NCT00146172
• Recruitment Status: Completed
• First Posted: September 5, 2005
• Results First Posted: February 13, 2018
• Last Update Posted: September 17, 2018
• Sponsor: Puma Biotechnology, Inc.
• Information provided by (Responsible Party): Puma Biotechnology, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Breast Neoplasms	Drug: neratinib	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 73 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: 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.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: November 2003
• Actual Primary Completion Date: January 2007
• Actual Study Completion Date: January 2007

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Dose Limiting Toxicity (DLT) [ Time Frame: 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.
2. Maximum Tolerated Dose (MTD) [ Time Frame: 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 :

1. Number of Participants With Best Overall Response [ Time Frame: 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.
2. Duration of Response [ Time Frame: From start date of response to first PD, up to 39 weeks. ]
   Duration of response of responders (PR+) by Kaplan-Meier estimate
3. Progression Free Survival [ Time Frame: 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.
4. Objective Response Rate [ Time Frame: From first dose date to progression/death or last assessment, up to 39 weeks ]
   Patients with PR or higher responses, evaluable population
5. Clinical Benefit Rate [ Time Frame: 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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Florida

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States, 33612

United States, Massachusetts

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02115

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

United States, Ohio

The Cleveland Clinic Foundation Taussig Cancer Center

Cleveland, Ohio, United States, 44195

United States, Tennessee

The Sarah Cannon Cancer Center

Nashville, Tennessee, United States, 37203

Sponsors and Collaborators

Puma Biotechnology, Inc.

Investigators

• Study Director: Puma; Biotechnology

More Information

• Responsible Party: Puma Biotechnology, Inc.
• ClinicalTrials.gov Identifier: NCT00146172
• Other Study ID Numbers: 3144A1-102
• First Posted: September 5, 2005
• Results First Posted: February 13, 2018
• Last Update Posted: September 17, 2018
• Last Verified: August 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Puma Biotechnology, Inc.:

Tumors; Neratinib; HKI-272; Nerlynx

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases