Study Evaluating Neratinib (HKI-272) In Combination With Vinorelbine In Subjects With Solid Tumors And Metastatic Breast Cancer
- Conditions
- Breast CancerAdvanced Malignant Solid Tumors
- Interventions
- Registration Number
- NCT00706030
- Lead Sponsor
- Puma Biotechnology, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 92
- 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).
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description neratinib 160 mg + vinorelbine neratinib 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 neratinib 160 mg + vinorelbine 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 neratinib 240 mg + vinorelbine neratinib 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 neratinib 240 mg + vinorelbine 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 neratinib 240 mg + vinorelbine, No Prior Lapatinib neratinib 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 neratinib 240 mg + vinorelbine, No Prior Lapatinib 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 neratinib 240 mg + vinorelbine, Prior Lapatinib neratinib 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 neratinib 240 mg + vinorelbine, Prior Lapatinib 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
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose From Day 1 to Day 21. Maximum Tolerated Dose (MTD) of Neratinib in combination with vinorelbine in subjects with advanced solid tumors.
Overall Response Rate 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.
- Secondary Outcome Measures
Name Time Method Progression-Free Survival 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.
Clinical Benefit Rate 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.
Duration Of Response 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.
Trial Locations
- Locations (35)
Albert Einstein Cancer Center
🇺🇸Bronx, New York, United States
Centre Paul Papin
🇫🇷Angers, France
Centro Oncologico de Galicia
🇪🇸A Coruña, Spain
Southampton General Hospital
🇬🇧Southampton, Hampshire, United Kingdom
Martini Ziekenhuis / Afdeling Interne Geneeskunde
🇳🇱Groningen, Netherlands
Cancer Hospital, Chinese Academy of Medical Sciences
🇨🇳Beijing, Beijing, China
The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army
🇨🇳Beijing, Beijing, China
Institut Curie, Département d'Oncologie Médicale
🇫🇷Paris, France
Highlands Oncology Group
🇺🇸Fayetteville, Arkansas, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
Hematology Oncology Associates of Rockland
🇺🇸Nyack, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Carolinas Hematology-Oncology Associates
🇺🇸Charlotte, North Carolina, United States
AZ Klina Brasschaat
🇧🇪Brasschaat, Belgium
St.-Augustinus Hospital Oncology Department
🇧🇪Wilrijk, Belgium
Institut Jules Bordet
🇧🇪Brussels, Belgium
Chinese People's Liberation Army General Hospital
🇨🇳Beijing, Beijing, China
Tianjin Cancer Hospital
🇨🇳TianJin, Tianjin, China
Institut Paoli Calmette
🇫🇷Marseille, France
Institut Claudius Regaud
🇫🇷Toulouse, France
Queen Mary Hospital
ðŸ‡ðŸ‡°Hong Kong, Hong Kong
Wojskowy Instytut Medyczny, Klinika Onkologii
🇵🇱Warszawa, Poland
Centrum Onkologii Ziemii Lubelskiej, Oddział Chemioterapii
🇵🇱Lublin, Poland
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Hospital Arnau de Vilanova, Servicio de Oncologia Medica
🇪🇸Lleida, Spain
Hospital 12 de Octubre, Servicio de Oncologia Medica
🇪🇸Madrid, Spain
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Onkologiska Kliniken Universitetssjukhuset i Lund
🇸🇪Lund, Sweden
Christie NHS Foundation Trust
🇬🇧Manchester, Lancashire, United Kingdom
Velindre Cancer Centre
🇬🇧Cardiff, United Kingdom
Guy's and St. Thomas' NHS Foundation Trust, Guy's Hospital
🇬🇧London, United Kingdom
Broomfield Hospital
🇬🇧Chelmsford, Essex, United Kingdom
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
UNIMED Medical Institute
ðŸ‡ðŸ‡°Hong Kong, Hong Kong