Clinical trial NCT00445458: A Phase 1/2 Study of HKI-272 (Neratinib) in Combination With Paclitaxel (Taxol) in Subjects With Solid Tumors and Breast Cancer
Official title: A Phase 1/2 Study of HKI-272 in Combination With Paclitaxel in Subjects With Solid Tumors and Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced Breast Cancer
Advanced Malignant Solid Tumors
Breast Neoplasms
Keywords: cancer
HKI-272
neratinib
paclitaxel
Taxol
breast cancer
Nerlynx
Lead sponsor: Puma Biotechnology, Inc.
Sponsor class: INDUSTRY
First posted: 2007-03-09
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

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:

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

Primary outcomes:
measure: Dose Limiting Toxicity Incidence of Neratinib in Combination With Paclitaxel
timeFrame: From first dose date through day 28
measure: Maximum Tolerated Dose
timeFrame: From first dose date through day 28.
measure: Objective Response Rate
timeFrame: From first dose date to progression or last tumor assessment, up to 140 weeks
Secondary outcomes:
measure: Maximum Plasma Concentration of Neratinib
timeFrame: 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.
measure: Area Under the Concentration-time Curve 0-24
timeFrame: 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.
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Scripps, Clinic General
state: California
city: La Jolla
country: United States
facility: Moores UC San Diego Cancer Center
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: Boston
country: United States
facility: Boston University Medical Center
state: Massachusetts
city: Lansing
country: United States
facility: Mid-Michigan Physicians-HOS Division
state: Michigan
city: Saint Joseph
country: United States
facility: Oncology Care Associates
state: Michigan
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: San Antonio
country: United States
facility: CTRC at The University of Texas Health Science Center
state: Texas
city: Brussels
country: Belgium
facility: Institut Jules Bordet Unite du Chimiotherapie
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Kortrijk
country: Belgium
facility: AZ Groeninge Campus Maria's Voorzienigheid (MV)
city: Wilrijk
country: Belgium
facility: Oncologisch Centrum GZA - Location St Augustinus
city: Toronto
country: Canada
facility: Princess Margaret Hospital University Health Network
state: Ontario
city: Beijing
country: China
facility: The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army
state: Beijing
city: Beijing
country: China
facility: Chinese People's Liberation Army General Hospital
state: Beijing
city: TianJin
country: China
facility: Tianjin Cancer Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Union Medicine Center Department of Oncology
state: Tianjin
city: Beijing
country: China
facility: Cancer Hospital, Chinese Academy of Medical Sciences
city: Beijing
country: China
facility: Peking Union Medical College Hospital of Chinese Academy of Medical Sciences
city: Hong Kong
country: Hong Kong
facility: UNIMED Medical Institute
city: Hong Kong
country: Hong Kong
facility: Department of Medicine, Queen Mary Hospital
city: Hong Kong
country: Hong Kong
facility: Department of Surgery Queen Mary Hospital
city: Pune
country: India
facility: Jehangir Clinical Development Centre, Jehangir Hospital Premises
state: Maharashtra
city: Pune
country: India
facility: M.M.F. Joshi Hospital & Ratna Memorial Hospital
state: Maharashtra
city: Mumbai
country: India
facility: Tata Memorial Hospital
state: Parel
city: Jaipur
country: India
facility: Birla Cancer Centre, S.M.S. Medical College & Hospital
state: Rajasthan
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System - Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center, Division of Oncology, Department of Internal Medicine
city: Krakow
country: Poland
facility: Wojewodzki Szpital Specjalistyczny im. Ludwika Rydygiera, Oddzial Onkologii
city: Lublin
country: Poland
facility: Oddzial Chemioterapii Centrum Onkologii Ziemii Lubelskiej
city: Dnipropetrovsk
country: Ukraine
facility: City Multifield Clinical Hospital #4 Department of chemotherapy, Dnipropetrovs'k State Medical Academy, Chair of Oncology and Medical Radiology
city: Lviv
country: Ukraine
facility: State Oncological Regional Treatment and Diagnostic Center Department of chemotherapy
Study officials:
affiliation: Biotechnology
name: Puma
role: STUDY_DIRECTOR
References:
citation: 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.