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Study Evaluating HKI-272 in Tumors

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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:
Information provided by (Responsible Party):
Puma Biotechnology, Inc.

September 2, 2005
September 5, 2005
August 10, 2017
February 13, 2018
September 17, 2018
November 2003
January 2007   (Final data collection date for primary outcome measure)
  • 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.
  • 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.
Adverse events will be assessed on a continuous basis, physical exam, ECG, and ECOG performance status will be done at the beginning of every 1 month cycle. Laboratory evaluations will be performed approximately every 14 days.
Complete list of historical versions of study NCT00146172 on ClinicalTrials.gov Archive Site
  • 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.
  • 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
  • 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.
  • 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
  • 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
Tumor assessment at screening and at the end of cycles 2, 4, and 6. Pharmacokinetics blood samples throughout study, inlcuding 8 hour PK day (sample every hour) on study day 14. Pharmacodynamic blood sample at screening and day 14.
Not Provided
Not Provided
 
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.
Not Provided
Interventional
Phase 1
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
Breast Neoplasms
Drug: neratinib
HKI-272
  • Experimental: Neratinib 40 mg
    Intervention: Drug: neratinib
  • Experimental: Neratinib 80 mg
    Intervention: Drug: neratinib
  • Experimental: Neratinib 120 mg
    Intervention: Drug: neratinib
  • Experimental: Neratinib 180 mg
    Intervention: Drug: neratinib
  • Experimental: Neratinib 240 mg
    Intervention: Drug: neratinib
  • Experimental: Neratinib 320 mg
    Intervention: Drug: neratinib
  • Experimental: Neratinib 400 mg
    Intervention: Drug: neratinib
  • Experimental: Neratinib 320 mg MTD
    Intervention: Drug: neratinib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
73
88
January 2007
January 2007   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00146172
3144A1-102
Not Provided
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
Puma Biotechnology, Inc.
Puma Biotechnology, Inc.
Not Provided
Study Director: Puma Biotechnology
Puma Biotechnology, Inc.
August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP