A Phase 1/2 Study of HKI-272 (Neratinib) in Combination With Paclitaxel (Taxol) in Subjects With Solid Tumors and Breast Cancer
A Phase 1/2 Study of HKI-272 in Combination With Paclitaxel in Subjects With Solid Tumors and Breast Cancer
1 other identifier
interventional
110
9 countries
32
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2007
Longer than P75 for phase_1
32 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
First Submitted
Initial submission to the registry
March 8, 2007
CompletedFirst Posted
Study publicly available on registry
March 9, 2007
CompletedStudy Start
First participant enrolled
September 11, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
February 7, 2018
CompletedResults Posted
Study results publicly available
May 9, 2018
CompletedJuly 26, 2018
June 1, 2018
3.6 years
March 8, 2007
August 10, 2017
June 27, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Dose Limiting Toxicity Incidence of Neratinib in Combination With Paclitaxel
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
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
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 Outcomes (2)
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.
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.
Study Arms (4)
HKI-272 dose level 1
EXPERIMENTALPart 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
EXPERIMENTALPart 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
EXPERIMENTALPart 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
EXPERIMENTALPart 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.
Interventions
Eligibility Criteria
You may qualify if:
- 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
- \- Pathologically confirmed solid tumor not curable with available standard therapy
- Pathologically confirmed breast cancer
- HER2 positive tumor
- Prior treatment with Herceptin
You may not qualify if:
- 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
- \- More than 1 (arm A) or 3 (arm B) prior cytotoxic chemotherapy regimen for metastatic disease
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (32)
Scripps, Clinic General
La Jolla, California, 92037, United States
Moores UC San Diego Cancer Center
La Jolla, California, 92093, United States
Sharp Memorial Hospital
San Diego, California, 92123, United States
Boston University Medical Center
Boston, Massachusetts, 02118, United States
Mid-Michigan Physicians-HOS Division
Lansing, Michigan, 48912, United States
Oncology Care Associates
Saint Joseph, Michigan, 49085, United States
Columbia University Medical Center
New York, New York, 10032, United States
CTRC at The University of Texas Health Science Center
San Antonio, Texas, 78229, United States
Institut Jules Bordet Unite du Chimiotherapie
Brussels, 1000, Belgium
Universitair Ziekenhuis Gent
Ghent, 9000, Belgium
AZ Groeninge Campus Maria's Voorzienigheid (MV)
Kortrijk, 8500, Belgium
Oncologisch Centrum GZA - Location St Augustinus
Wilrijk, 2610, Belgium
Princess Margaret Hospital University Health Network
Toronto, Ontario, M5G 2M9, Canada
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
Tianjin Union Medicine Center Department of Oncology
Tianjin, Tianjin Municipality, 300121, China
Cancer Hospital, Chinese Academy of Medical Sciences
Beijing, 100021, China
Peking Union Medical College Hospital of Chinese Academy of Medical Sciences
Beijing, 100032, China
UNIMED Medical Institute
Hong Kong, 0, Hong Kong
Department of Medicine, Queen Mary Hospital
Hong Kong, Hong Kong
Department of Surgery Queen Mary Hospital
Hong Kong, Hong Kong
Jehangir Clinical Development Centre, Jehangir Hospital Premises
Pune, Maharashtra, 411001, India
M.M.F. Joshi Hospital & Ratna Memorial Hospital
Pune, Maharashtra, 411004, India
Tata Memorial Hospital
Mumbai, Parel, 400012, India
Birla Cancer Centre, S.M.S. Medical College & Hospital
Jaipur, Rajasthan, 302004, India
Wojewodzki Szpital Specjalistyczny im. Ludwika Rydygiera, Oddzial Onkologii
Krakow, 31-826, Poland
Oddzial Chemioterapii Centrum Onkologii Ziemii Lubelskiej
Lublin, 20-090, Poland
Yonsei University Health System - Severance Hospital
Seoul, 120-752, South Korea
Asan Medical Center, Division of Oncology, Department of Internal Medicine
Seoul, 138-736, South Korea
City Multifield Clinical Hospital #4 Department of chemotherapy, Dnipropetrovs'k State Medical Academy, Chair of Oncology and Medical Radiology
Dnipropetrovsk, 49102, Ukraine
State Oncological Regional Treatment and Diagnostic Center Department of chemotherapy
Lviv, 79031, Ukraine
Related Publications (1)
Chow LW, Xu B, Gupta S, Freyman A, Zhao Y, Abbas R, Vo Van ML, Bondarenko I. Combination neratinib (HKI-272) and paclitaxel therapy in patients with HER2-positive metastatic breast cancer. Br J Cancer. 2013 May 28;108(10):1985-93. doi: 10.1038/bjc.2013.178. Epub 2013 Apr 30.
PMID: 23632474DERIVED
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
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 8, 2007
First Posted
March 9, 2007
Study Start
September 11, 2007
Primary Completion
May 1, 2011
Study Completion
February 7, 2018
Last Updated
July 26, 2018
Results First Posted
May 9, 2018
Record last verified: 2018-06