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

June 27, 2018 updated by: Puma Biotechnology, Inc.

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

110

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Brussels, Belgium, 1000
        • Institut Jules Bordet Unite du Chimiotherapie
      • Gent, Belgium, 9000
        • Universitair Ziekenhuis Gent
      • Kortrijk, Belgium, 8500
        • AZ Groeninge Campus Maria's Voorzienigheid (MV)
      • Wilrijk, Belgium, 2610
        • Oncologisch Centrum GZA - Location St Augustinus
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Hospital University Health Network
  • China
      • Beijing, China, 100021
        • Cancer Hospital, Chinese Academy of Medical Sciences
      • Beijing, China, 100032
        • Peking Union Medical College Hospital of Chinese Academy of Medical Sciences
    • Beijing
      • Beijing, Beijing, China, 100071
        • The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army
      • Beijing, Beijing, China, 100853
        • Chinese People's Liberation Army General Hospital
    • Tianjin
      • TianJin, Tianjin, China, 300060
        • Tianjin Cancer Hospital
      • Tianjin, Tianjin, China, 300121
        • Tianjin Union Medicine Center Department of Oncology
  • Hong Kong
      • Hong Kong, Hong Kong
        • Department of Medicine, Queen Mary Hospital
      • Hong Kong, Hong Kong
        • UNIMED Medical Institute
      • Hong Kong, Hong Kong
        • Department of Surgery Queen Mary Hospital
  • India
    • Maharashtra
      • Pune, Maharashtra, India, 411001
        • Jehangir Clinical Development Centre, Jehangir Hospital Premises
      • Pune, Maharashtra, India, 411004
        • M.M.F. Joshi Hospital & Ratna Memorial Hospital
    • Parel
      • Mumbai, Parel, India, 400012
        • Tata Memorial Hospital
    • Rajasthan
      • Jaipur, Rajasthan, India, 302004
        • Birla Cancer Centre, S.M.S. Medical College & Hospital
  • Korea, Republic of
      • Seoul, Korea, Republic of, 120-752
        • Yonsei University Health System - Severance Hospital
      • Seoul, Korea, Republic of, 138-736
        • Asan Medical Center, Division of Oncology, Department of Internal Medicine
  • Poland
      • Krakow, Poland, 31-826
        • Wojewodzki Szpital Specjalistyczny im. Ludwika Rydygiera, Oddzial Onkologii
      • Lublin, Poland, 20-090
        • Oddzial Chemioterapii Centrum Onkologii Ziemii Lubelskiej
  • Ukraine
      • Dnipropetrovsk, Ukraine, 49102
        • City Multifield Clinical Hospital #4 Department of chemotherapy, Dnipropetrovs'k State Medical Academy, Chair of Oncology and Medical Radiology
      • Lviv, Ukraine, 79031
        • State Oncological Regional Treatment and Diagnostic Center Department of chemotherapy
  • United States
    • California
      • La Jolla, California, United States, 92093
        • Moores UC San Diego Cancer Center
      • La Jolla, California, United States, 92037
        • Scripps, Clinic General
      • San Diego, California, United States, 92123
        • Sharp Memorial Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston University Medical Center
    • Michigan
      • Lansing, Michigan, United States, 48912
        • Mid-Michigan Physicians-HOS Division
      • Saint Joseph, Michigan, United States, 49085
        • Oncology Care Associates
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
    • Texas
      • San Antonio, Texas, United States, 78229
        • CTRC at The University of Texas Health Science Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: Paclitaxel
Drug: HKI-272
Other Names:
  • Neratinib
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.
Drug: Paclitaxel
Drug: HKI-272
Other Names:
  • Neratinib
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.
Drug: Paclitaxel
Drug: HKI-272
Other Names:
  • Neratinib
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.
Drug: Paclitaxel
Drug: HKI-272
Other Names:
  • Neratinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From first dose date through day 28
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.
From first dose date through day 28.
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.
From first dose date to progression or last tumor assessment, up to 140 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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 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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Puma Biotechnology, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 11, 2007

Primary Completion (Actual)

May 1, 2011

Study Completion (Actual)

February 7, 2018

Study Registration Dates

First Submitted

March 8, 2007

First Submitted That Met QC Criteria

March 8, 2007

First Posted (Estimate)

March 9, 2007

Study Record Updates

Last Update Posted (Actual)

July 26, 2018

Last Update Submitted That Met QC Criteria

June 27, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3144A1-203 / B1891014

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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