Clinical trial NCT00706030: Study Evaluating Neratinib (HKI-272) In Combination With Vinorelbine In Subjects With Solid Tumors And Metastatic Breast Cancer
Official title: A Phase 1/2 Study Of HKI-272 In Combination With Vinorelbine In Subjects With Solid Tumors And Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Advanced Malignant Solid Tumors
Keywords: Metastatic breast cancer
HKI-272
Neratinib
Nerlynx
PB-272
Lead sponsor: Puma Biotechnology, Inc.
Sponsor class: INDUSTRY
First posted: 2008-06-27
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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).

Primary outcomes:
measure: Overall Response Rate
timeFrame: From first dose date to progression or last tumor assessment, up to four years and six months.
measure: Maximum Tolerated Dose
timeFrame: From Day 1 to Day 21.
Secondary outcomes:
measure: Clinical Benefit Rate
timeFrame: From first dose date to progression or last tumor assessment, up to four years and six months.
measure: Progression-Free Survival
timeFrame: From first dose date to progression or death, up to four years and six months.
measure: Duration Of Response
timeFrame: From start date of response to first PD/death, up to four years and six months.
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Bronx
country: United States
facility: Albert Einstein Cancer Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Nyack
country: United States
facility: Hematology Oncology Associates of Rockland
state: New York
city: Charlotte
country: United States
facility: Carolinas Hematology-Oncology Associates
state: North Carolina
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Brasschaat
country: Belgium
facility: AZ Klina Brasschaat
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Wilrijk
country: Belgium
facility: St.-Augustinus Hospital Oncology Department
city: Beijing
country: China
facility: Cancer Hospital, Chinese Academy of Medical Sciences
state: Beijing
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: Angers
country: France
facility: Centre Paul Papin
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Paris
country: France
facility: Institut Curie, Département d'Oncologie Médicale
city: Toulouse
country: France
facility: Institut Claudius Regaud
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Hong Kong
country: Hong Kong
facility: UNIMED Medical Institute
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis / Afdeling Interne Geneeskunde
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemii Lubelskiej, Oddział Chemioterapii
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny, Klinika Onkologii
city: A Coruña
country: Spain
facility: Centro Oncologico de Galicia
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Lleida
country: Spain
facility: Hospital Arnau de Vilanova, Servicio de Oncologia Medica
city: Madrid
country: Spain
facility: Hospital 12 de Octubre, Servicio de Oncologia Medica
city: Lund
country: Sweden
facility: Onkologiska Kliniken Universitetssjukhuset i Lund
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Chelmsford
country: United Kingdom
facility: Broomfield Hospital
state: Essex
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: Hampshire
city: Manchester
country: United Kingdom
facility: Christie NHS Foundation Trust
state: Lancashire
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: London
country: United Kingdom
facility: Guy's and St. Thomas' NHS Foundation Trust, Guy's Hospital
Study officials:
affiliation: Biotechnology
name: Puma
role: STUDY_DIRECTOR
References:
citation: 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.