Study Evaluating Neratinib (HKI-272) In Combination With Vinorelbine In Subjects With Solid Tumors And Metastatic Breast Cancer
A Phase 1/2 Study Of HKI-272 In Combination With Vinorelbine In Subjects With Solid Tumors And Metastatic Breast Cancer
1 other identifier
interventional
92
11 countries
35
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 breast-cancer
Started Apr 2008
Longer than P75 for phase_1 breast-cancer
35 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
April 29, 2008
CompletedFirst Submitted
Initial submission to the registry
June 25, 2008
CompletedFirst Posted
Study publicly available on registry
June 27, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2009
CompletedResults Posted
Study results publicly available
May 8, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
June 7, 2018
CompletedAugust 9, 2018
June 1, 2018
1.4 years
June 25, 2008
August 10, 2017
July 11, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Overall Response Rate
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
Maximum Tolerated Dose (MTD) of Neratinib in combination with vinorelbine in subjects with advanced solid tumors.
From Day 1 to Day 21.
Secondary Outcomes (3)
Clinical Benefit Rate
From first dose date to progression or last tumor assessment, up to four years and six months.
Progression-Free Survival
From first dose date to progression or death, up to four years and six months.
Duration Of Response
From start date of response to first PD/death, up to four years and six months.
Study Arms (4)
neratinib 160 mg + vinorelbine
EXPERIMENTALneratinib 160 mg tablets administered daily by mouth, vinorelbine 25 mg/m\^2 administered IV on day 1 and day 8 of 21 day cycle
neratinib 240 mg + vinorelbine
EXPERIMENTALneratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m\^2 administered IV on day 1 and day 8 of 21 day cycle
neratinib 240 mg + vinorelbine, No Prior Lapatinib
EXPERIMENTALneratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m\^2 administered IV on day 1 and day 8 of 21 day cycle
neratinib 240 mg + vinorelbine, Prior Lapatinib
EXPERIMENTALneratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m\^2 administered IV on day 1 and day 8 of 21 day cycle
Interventions
Eligibility Criteria
You may qualify if:
- 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).
You may not qualify if:
- 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).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (35)
Highlands Oncology Group
Fayetteville, Arkansas, 72703, United States
City of Hope National Medical Center
Duarte, California, 91010, United States
Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756, United States
Columbia University Medical Center
New York, New York, 10032, United States
Hematology Oncology Associates of Rockland
Nyack, New York, 10960, United States
Albert Einstein Cancer Center
The Bronx, New York, 10461, United States
Carolinas Hematology-Oncology Associates
Charlotte, North Carolina, 28203, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
AZ Klina Brasschaat
Brasschaat, 2930, Belgium
Institut Jules Bordet
Brussels, 1000, Belgium
St.-Augustinus Hospital Oncology Department
Wilrijk, 2610, Belgium
Cancer Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, 100021, China
The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army
Beijing, Beijing Municipality, 100071, China
Chinese People's Liberation Army General Hospital
Beijing, Beijing Municipality, 100853, China
Tianjin Cancer Hospital
Tianjin, Tianjin Municipality, 300060, China
Centre Paul Papin
Angers, 49100, France
Institut Paoli Calmette
Marseille, 13272, France
Institut Curie, Département d'Oncologie Médicale
Paris, 75248, France
Institut Claudius Regaud
Toulouse, 31052, France
Queen Mary Hospital
Hong Kong, Hong Kong
UNIMED Medical Institute
Hong Kong, Hong Kong
Martini Ziekenhuis / Afdeling Interne Geneeskunde
Groningen, 9728 NZ, Netherlands
Centrum Onkologii Ziemii Lubelskiej, Oddział Chemioterapii
Lublin, 20-090, Poland
Wojskowy Instytut Medyczny, Klinika Onkologii
Warsaw, 00-909, Poland
Centro Oncologico de Galicia
A Coruña, 15009, Spain
Hospital Clinic i Provincial de Barcelona
Barcelona, 08036, Spain
Hospital Arnau de Vilanova, Servicio de Oncologia Medica
Lleida, 25198, Spain
Hospital 12 de Octubre, Servicio de Oncologia Medica
Madrid, 28041, Spain
Onkologiska Kliniken Universitetssjukhuset i Lund
Lund, 22185, Sweden
National Taiwan University Hospital
Taipei, 100, Taiwan
Broomfield Hospital
Chelmsford, Essex, CM1 7ET, United Kingdom
Southampton General Hospital
Southampton, Hampshire, SO16 6YD, United Kingdom
Christie NHS Foundation Trust
Manchester, Lancashire, M20 4BX, United Kingdom
Velindre Cancer Centre
Cardiff, CF14 2TL, United Kingdom
Guy's and St. Thomas' NHS Foundation Trust, Guy's Hospital
London, SE1 9RT, United Kingdom
Related Publications (1)
Awada A, Dirix L, Manso Sanchez L, Xu B, Luu T, Dieras V, Hershman DL, Agrapart V, Ananthakrishnan R, Staroslawska E. Safety and efficacy of neratinib (HKI-272) plus vinorelbine in the treatment of patients with ErbB2-positive metastatic breast cancer pretreated with anti-HER2 therapy. Ann Oncol. 2013 Jan;24(1):109-16. doi: 10.1093/annonc/mds284. Epub 2012 Sep 11.
PMID: 22967996DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Senior Director, Clinical Operations
- Organization
- Puma Biotechnology, Inc.
Study Officials
- STUDY DIRECTOR
Puma
Biotechnology
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 25, 2008
First Posted
June 27, 2008
Study Start
April 29, 2008
Primary Completion
October 1, 2009
Study Completion
June 7, 2018
Last Updated
August 9, 2018
Results First Posted
May 8, 2018
Record last verified: 2018-06