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A Phase 1/2 Study of HKI-272 (Neratinib) in Combination With Paclitaxel (Taxol) in Subjects With Solid Tumors and Breast Cancer

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ClinicalTrials.gov Identifier: NCT00445458
Recruitment Status : Completed
First Posted : March 9, 2007
Results First Posted : May 9, 2018
Last Update Posted : July 25, 2018
Sponsor:
Information provided by (Responsible Party):
Puma Biotechnology, Inc.

Tracking Information
First Submitted Date  ICMJE March 8, 2007
First Posted Date  ICMJE March 9, 2007
Results First Submitted Date  ICMJE August 10, 2017
Results First Posted Date  ICMJE May 9, 2018
Last Update Posted Date July 25, 2018
Actual Study Start Date  ICMJE September 11, 2007
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 27, 2018)
  • Dose Limiting Toxicity Incidence of Neratinib in Combination With Paclitaxel [ Time Frame: From first dose date through day 28 ]
    Dose Limiting Toxicity in subjects with solid tumors treated with neratinib, administered daily, in combination with paclitaxel 80 mg/m² IV on days 1, 8, and 15 of a 28 day cycle.
  • Maximum Tolerated Dose [ Time Frame: From first dose date through day 28. ]
    Maximum Tolerated Dose (MTD) of neratinib, daily, in combination with paclitaxel 80 mg/m², intravenous at days 1, 8, and 15, associated with the dose limiting toxicity data.
  • Objective Response Rate [ Time Frame: From first dose date to progression or last tumor assessment, up to 140 weeks ]
    Subjects with partial response (PR) or complete response (CR) with ERBB2 positive breast cancer treated at the maximum tolerated dose (MTD) of neratinib in combination with paclitaxel, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: CR, disappearance of all target lesions; PR, >=30% decrease in the sum of the longest diameter of target lesions; and no progressive disease (PD) for non-target lesions, and no new lesions.
Original Primary Outcome Measures  ICMJE
 (submitted: March 8, 2007)
Physical Exams Adverse Event Assessment Radiographic Tumor Assessment (CT, MRI, bone scan)
Change History Complete list of historical versions of study NCT00445458 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2018)
  • Maximum Plasma Concentration of Neratinib [ Time Frame: Samples taken at 0 hour and at 1, 2, 4, 6, 8, and 24 hours postdose on Day 15 of Cycle 1, and 1 predose sample on Day 1 in Cycle 1. ]
    Maximum plasma concentration of neratinib; after each dosing of neratinib on Cycle 1 of Day 15, blood samples taken at regular time points.
  • Area Under the Concentration-time Curve 0-24 [ Time Frame: Samples taken at 0 hour and at 1, 2, 4, 6, 8, and 24 hours postdose on Day 15 of Cycle 1, and 1 predose sample on Day 1 in Cycle 1. ]
    Area under the concentration-time curve of neratinib; after each dosing of neratinib on Cycle 1 of Day 15, blood samples taken at regular time points.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 8, 2007)
ECG ECHO/MUGA Lab values
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1/2 Study of HKI-272 (Neratinib) in Combination With Paclitaxel (Taxol) in Subjects With Solid Tumors and Breast Cancer
Official Title  ICMJE A Phase 1/2 Study of HKI-272 in Combination With Paclitaxel in Subjects With Solid Tumors and Breast Cancer
Brief Summary The purpose of this study is to learn whether it is safe and effective to administer HKI-272 (neratinib) in combination with paclitaxel in patients with breast cancer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Breast Cancer
  • Advanced Malignant Solid Tumors
  • Breast Neoplasms
Intervention  ICMJE
  • Drug: HKI-272
    Other Name: Neratinib
  • Drug: Paclitaxel
Study Arms  ICMJE
  • Experimental: HKI-272 dose level 1
    Part 1: Subjects with solid tumors receiving HKI-272 (neratinib) 160 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV.
    Interventions:
    • Drug: HKI-272
    • Drug: Paclitaxel
  • Experimental: HKI-272 dose level 2
    Part 1: Subjects with solid tumors receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV.
    Interventions:
    • Drug: HKI-272
    • Drug: Paclitaxel
  • Experimental: HKI-272 expanded MTD cohort, arm A
    Part 2: Subjects with metastatic breast cancer who have not received more than 1 prior cytotoxic chemotherapy treatment regimen for metastatic disease receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV.
    Interventions:
    • Drug: HKI-272
    • Drug: Paclitaxel
  • Experimental: HKI-272 expanded MTD cohort, arm B
    Part 2: Subjects with metastatic breast cancer who have not received more than 3 prior cytotoxic chemotherapy treatment regimen for metastatic disease receiving HKI-272 (neratinib) 240 mg daily by mouth in combination with paclitaxel 80 mg/m^2 weekly IV.
    Interventions:
    • Drug: HKI-272
    • Drug: Paclitaxel
Publications * Chow LW, Xu B, Gupta S, Freyman A, Zhao Y, Abbas R, Vo Van ML, Bondarenko I. Combination neratinib (HKI-272) and paclitaxel therapy in patients with HER2-positive metastatic breast cancer. Br J Cancer. 2013 May 28;108(10):1985-93. doi: 10.1038/bjc.2013.178. Epub 2013 Apr 30.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 27, 2018)
110
Original Enrollment  ICMJE
 (submitted: March 8, 2007)
128
Actual Study Completion Date  ICMJE February 7, 2018
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Inclusion criteria for both parts of clinical trial:

  • Good performance status
  • Normal ejection fraction
  • Adequate cardiac, kidney, and liver function
  • Adequate blood counts
  • At least one measurable target lesion
  • Negative pregnancy test for female subjects

Inclusion Criteria for Part 1 Only:

- Pathologically confirmed solid tumor not curable with available standard therapy

Inclusion Criteria for Part 2 Only:

  • Pathologically confirmed breast cancer
  • HER2 positive tumor
  • Prior treatment with Herceptin

Exclusion Criteria:

Exclusion criteria for both parts of clinical trial:

  • Major surgery, radiotherapy, chemotherapy or investigational agents within two weeks of treatment day 1
  • Subjects with bone or skin as the only site of disease
  • Active central nervous system metastases
  • Significant cardiac disease or dysfunction
  • Significant gastrointestinal disorder
  • Inability or unwillingness to swallow HKI-272 capsules
  • Prior exposure to HKI-272 or other HER2 targeted agents, except trastuzumab (Part 2 only). Prior lapatinib is permitted in arm B of part 2.
  • Treatment with a taxane within 3 months of treatment day 1
  • Grade 2 or greater motor or sensory neuropathy
  • Pregnant or breast feeding women
  • Known hypersensitivity to paclitaxel or Cremophor EL
  • Prior treatment with anthracyclines with cumulative dose of >400 mg/m^2
  • Any other cancer within 5 years with the exception of contralateral breast cancer, adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin

Exclusion Criteria for Part 2 Only:

- More than 1 (arm A) or 3 (arm B) prior cytotoxic chemotherapy regimen for metastatic disease

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   China,   Hong Kong,   India,   Korea, Republic of,   Poland,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00445458
Other Study ID Numbers  ICMJE 3144A1-203 / B1891014
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Puma Biotechnology, Inc.
Study Sponsor  ICMJE Puma Biotechnology, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Puma Biotechnology
PRS Account Puma Biotechnology, Inc.
Verification Date June 2018

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