A Phase 1/2 Study of HKI-272 (Neratinib) in Combination With Paclitaxel (Taxol) in Subjects With Solid Tumors and Breast Cancer
- Conditions
- Advanced Breast CancerAdvanced Malignant Solid TumorsBreast Neoplasms
- Interventions
- Registration Number
- NCT00445458
- Lead Sponsor
- Puma Biotechnology, Inc.
- 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 available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 110
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 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description HKI-272 dose level 1 Paclitaxel 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. HKI-272 dose level 1 HKI-272 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. HKI-272 dose level 2 HKI-272 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. HKI-272 expanded MTD cohort, arm A HKI-272 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. HKI-272 expanded MTD cohort, arm B HKI-272 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. HKI-272 expanded MTD cohort, arm B Paclitaxel 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. HKI-272 dose level 2 Paclitaxel 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. HKI-272 expanded MTD cohort, arm A Paclitaxel 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.
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose 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 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.
Dose Limiting Toxicity Incidence of Neratinib in Combination With Paclitaxel 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.
- Secondary Outcome Measures
Name Time Method Area Under the Concentration-time Curve 0-24 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.
Maximum Plasma Concentration of Neratinib 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.
Trial Locations
- Locations (32)
Boston University Medical Center
🇺🇸Boston, Massachusetts, United States
Mid-Michigan Physicians-HOS Division
🇺🇸Lansing, Michigan, United States
Princess Margaret Hospital University Health Network
🇨🇦Toronto, Ontario, Canada
Birla Cancer Centre, S.M.S. Medical College & Hospital
🇮🇳Jaipur, Rajasthan, India
Oncologisch Centrum GZA - Location St Augustinus
🇧🇪Wilrijk, Belgium
AZ Groeninge Campus Maria's Voorzienigheid (MV)
🇧🇪Kortrijk, Belgium
Oncology Care Associates
🇺🇸Saint Joseph, Michigan, United States
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
Tata Memorial Hospital
🇮🇳Mumbai, Parel, India
State Oncological Regional Treatment and Diagnostic Center Department of chemotherapy
🇺🇦Lviv, Ukraine
Tianjin Cancer Hospital
🇨🇳TianJin, Tianjin, China
Chinese People's Liberation Army General Hospital
🇨🇳Beijing, Beijing, China
Tianjin Union Medicine Center Department of Oncology
🇨🇳Tianjin, Tianjin, China
Cancer Hospital, Chinese Academy of Medical Sciences
🇨🇳Beijing, China
Columbia University Medical Center
🇺🇸New York, New York, United States
Scripps, Clinic General
🇺🇸La Jolla, California, United States
Moores UC San Diego Cancer Center
🇺🇸La Jolla, California, United States
The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army
🇨🇳Beijing, Beijing, China
Institut Jules Bordet Unite du Chimiotherapie
🇧🇪Brussels, Belgium
Peking Union Medical College Hospital of Chinese Academy of Medical Sciences
🇨🇳Beijing, China
Asan Medical Center, Division of Oncology, Department of Internal Medicine
🇰🇷Seoul, Korea, Republic of
Yonsei University Health System - Severance Hospital
🇰🇷Seoul, Korea, Republic of
Oddzial Chemioterapii Centrum Onkologii Ziemii Lubelskiej
🇵🇱Lublin, Poland
City Multifield Clinical Hospital #4 Department of chemotherapy, Dnipropetrovs'k State Medical Academy, Chair of Oncology and Medical Radiology
🇺🇦Dnipropetrovsk, Ukraine
Jehangir Clinical Development Centre, Jehangir Hospital Premises
🇮🇳Pune, Maharashtra, India
Wojewodzki Szpital Specjalistyczny im. Ludwika Rydygiera, Oddzial Onkologii
🇵🇱Krakow, Poland
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
M.M.F. Joshi Hospital & Ratna Memorial Hospital
🇮🇳Pune, Maharashtra, India
CTRC at The University of Texas Health Science Center
🇺🇸San Antonio, Texas, United States
UNIMED Medical Institute
🇭🇰Hong Kong, Hong Kong
Department of Medicine, Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Department of Surgery Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong