Study Evaluating Neratinib (HKI-272) In Combination With Vinorelbine In Subjects With Solid Tumors And Metastatic Breast Cancer

July 11, 2018 updated by: Puma Biotechnology, Inc.

A Phase 1/2 Study Of HKI-272 In Combination With Vinorelbine In Subjects With Solid Tumors And Metastatic Breast Cancer

The purpose of this study is to identify the highest tolerable dose of neratinib (HKI-272) in combination with vinorelbine and to assess the safety of the combination of the two drugs as well as to obtain preliminary information on whether the combination of the two drugs has any effect on solid tumors.

The study will be conducted in two parts. In the first part, testing will be done on up to 12 subjects to determine the highest tolerable dose of HKI-272 and vinorelbine in patients with advanced solid tumors. In the second part of the study, approximately 60 additional subjects with metastatic ErbB-2-positive breast cancer, with no prior exposure to lapatinib, are planned to be added to better define the tolerability and preliminary activity of HKI-272 in combination with vinorelbine. Up to 20 additional subjects with ErbB-2-positive breast cancer with prior lapatinib exposure are also planned to be enrolled in part 2 for exploratory analyses.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

92

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
      • Brasschaat, Belgium, 2930
        • AZ KLINA Brasschaat
      • Brussels, Belgium, 1000
        • Institut Jules Bordet
      • Wilrijk, Belgium, 2610
        • St.-Augustinus Hospital Oncology Department
  • China
    • Beijing
      • Beijing, Beijing, China, 100021
        • Cancer Hospital, Chinese Academy of Medical Sciences
      • 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
  • France
      • Angers, France, 49100
        • Centre Paul Papin
      • Marseille, France, 13272
        • Institut Paoli Calmette
      • Paris, France, 75248
        • Institut Curie, Departement d'Oncologie Medicale
      • Toulouse, France, 31052
        • Institut Claudius Regaud
  • Hong Kong
      • Hong Kong, Hong Kong
        • Queen Mary Hospital
      • Hong Kong, Hong Kong
        • UNIMED Medical Institute
  • Netherlands
      • Groningen, Netherlands, 9728 NZ
        • Martini Ziekenhuis / Afdeling Interne Geneeskunde
  • Poland
      • Lublin, Poland, 20-090
        • Centrum Onkologii Ziemii Lubelskiej, Oddział Chemioterapii
      • Warszawa, Poland, 00-909
        • Wojskowy Instytut Medyczny, Klinika Onkologii
  • Spain
      • A Coruña, Spain, 15009
        • Centro Oncológico de Galicia
      • Barcelona, Spain, 08036
        • Hospital Clinic i Provincial de Barcelona
      • Lleida, Spain, 25198
        • Hospital Arnau de Vilanova, Servicio de Oncologia Medica
      • Madrid, Spain, 28041
        • Hospital 12 de Octubre, Servicio de Oncologia Medica
  • Sweden
      • Lund, Sweden, 22185
        • Onkologiska Kliniken Universitetssjukhuset i Lund
  • Taiwan
      • Taipei, Taiwan, 100
        • National Taiwan University Hospital
  • United Kingdom
      • Cardiff, United Kingdom, CF14 2TL
        • Velindre Cancer Centre
      • London, United Kingdom, SE1 9RT
        • Guy's and St. Thomas' NHS Foundation Trust, Guy's Hospital
    • Essex
      • Chelmsford, Essex, United Kingdom, CM1 7ET
        • Broomfield Hospital
    • Hampshire
      • Southampton, Hampshire, United Kingdom, SO16 6YD
        • Southampton General Hospital
    • Lancashire
      • Manchester, Lancashire, United Kingdom, M20 4BX
        • Christie NHS Foundation Trust
  • United States
    • Arkansas
      • Fayetteville, Arkansas, United States, 72703
        • Highlands Oncology Group
    • California
      • Duarte, California, United States, 91010
        • City of Hope National Medical Center
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center
    • New York
      • Bronx, New York, United States, 10461
        • Albert Einstein Cancer Center
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • Nyack, New York, United States, 10960
        • Hematology Oncology Associates of Rockland
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Carolinas Hematology-Oncology Associates
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer 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:

  • Confirmed pathologic diagnosis of a solid tumor that is not curable with available therapies for which HKI-272 plus vinorelbine is a reasonable treatment option (part 1 only) or Confirmed pathologic diagnosis of ErbB-2-positive breast cancer (current stage IV) in female subjects for which vinorelbine plus HKI-272 is a reasonable treatment option (part 2 only).
  • At least 1 prior antineoplastic chemotherapy treatment regimen for metastatic disease and at least 1 prior treatment with a trastuzumab-containing regimen for at least 6 weeks, for metastatic disease or subject relapsing under adjuvant treatment (part 2 only).
  • At least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST).

Exclusion Criteria:

  • More than 2 prior antineoplastic treatment regimens (excluding hormonotherapy) for metastatic disease. Subjects who relapsed under adjuvant treatment shouldn't have received more than one line of chemotherapy for metastatic disease (part 2 only).
  • Prior treatment with vinorelbine for metastatic setting, or prior treatment with any ErbB-2 targeted agents except trastuzumab (part 2 only). Up to 20 subjects with ErbB-2-overexpressing metastatic breast cancer who have been previously exposed to lapatinib but are not refractory to lapatinib may be enrolled in part 2.
  • Prior treatment with anthracyclines with a cumulative dose of doxorubicin of greater than 400 mg/m2, or of epirubicin dose of greater than 800 mg/m2, or the equivalent dose for other anthracyclines or derivatives (part 2 only).

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: SEQUENTIAL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: neratinib 160 mg + vinorelbine
neratinib 160 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle
Drug: neratinib
Other Names:
  • HKI-272
  • Nerlynx
Drug: vinorelbine
EXPERIMENTAL: neratinib 240 mg + vinorelbine
neratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle
Drug: neratinib
Other Names:
  • HKI-272
  • Nerlynx
Drug: vinorelbine
EXPERIMENTAL: neratinib 240 mg + vinorelbine, No Prior Lapatinib
neratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle
Drug: neratinib
Other Names:
  • HKI-272
  • Nerlynx
Drug: vinorelbine
EXPERIMENTAL: neratinib 240 mg + vinorelbine, Prior Lapatinib
neratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle
Drug: neratinib
Other Names:
  • HKI-272
  • Nerlynx
Drug: vinorelbine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate
Time Frame: From first dose date to progression or last tumor assessment, up to four years and six months.
Overall Response Rate (ORR), subjects with CR or PR by independent review in subjects with ErbB-2-positive breast cancer treated at the MTD of neratinib in combination with vinorelbine per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.
From first dose date to progression or last tumor assessment, up to four years and six months.
Maximum Tolerated Dose
Time Frame: From Day 1 to Day 21.
Maximum Tolerated Dose (MTD) of Neratinib in combination with vinorelbine in subjects with advanced solid tumors.
From Day 1 to Day 21.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Benefit Rate
Time Frame: From first dose date to progression or last tumor assessment, up to four years and six months.
Percentage of participants with partial response (PR) or complete response (CR) or stable disease > 24 weeks by independent assessment for subjects with ErbB-2-positive breast cancer treated at the MTD of neratinib in combination with vinorelbine, per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.
From first dose date to progression or last tumor assessment, up to four years and six months.
Progression-Free Survival
Time Frame: From first dose date to progression or death, up to four years and six months.
Number of weeks between the date of the first dose of test article and the first date of disease recurrence or progression, or death due to any cause, was documented, censored at the last evaluation, investigator assessment. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (v1.0), as at least a 20% increase in the sum of the longest diameters (LD) of target lesions, taking as reference the nadir LD, meaning the smallest sum of the LDs recorded since the treatment started; or unequivocal progression of existing nontarget lesions; or the appearance of any new lesions.
From first dose date to progression or death, up to four years and six months.
Duration Of Response
Time Frame: From start date of response to first PD/death, up to four years and six months.
Duration of response for subjects who had complete or partial response from first response to disease progression, death or last assessment per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.
From start date of response to first PD/death, up to four years and six months.

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)

April 29, 2008

Primary Completion (ACTUAL)

October 1, 2009

Study Completion (ACTUAL)

June 7, 2018

Study Registration Dates

First Submitted

June 25, 2008

First Submitted That Met QC Criteria

June 25, 2008

First Posted (ESTIMATE)

June 27, 2008

Study Record Updates

Last Update Posted (ACTUAL)

August 9, 2018

Last Update Submitted That Met QC Criteria

July 11, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3144A1-2204 / B1891015

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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