Clinical trial NCT00741260: Study Evaluating The Combination Of Neratinib And Capecitabine In Solid Tumors And Breast Cancer
Official title: A Phase 1/2, Open-Label Study Of Neratinib (HKI-272) In Combination With Capecitabine In Subjects With Solid Tumors And ErbB-2 Positive Metastatic Or Locally Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Breast Cancer
Keywords: Solid Tumor
erbB2+ Breast Cancer
Prior trastuzumab
Metastatic
Neratinib
HKI-272
Nerlynx
HER2
PB-272
Lead sponsor: Puma Biotechnology, Inc.
Sponsor class: INDUSTRY
First posted: 2008-08-26
Enrollment: 105
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: This is a world wide phase 1/2, open-label, study of neratinib in combination with capecitabine, conducted in 2 parts.

In Part 1, 3 to 9 subjects with solid tumors will be enrolled in each dose group of the combination of neratinib and capecitabine. Each subject will participate in only 1 dose group.

Additional subjects may be included at any dose level to further assess the safety and tolerability at that dose level.

In Part 2, up to 60 subjects with erbB-2 positive metastatic breast cancer will receive treatment with the combination of neratinib and capecitabine at the maximum tolerated dose level, as determined in Part 1. In addition 20 subjects with prior lapatinib exposure will be enrolled in Part 2.

Depending on the safety and activity profile observed during the dose escalation phase, the dose selected for Part 2 may be adjusted, if appropriate. In case one test article of the combination is discontinued due to intolerance the other test article can be administered alone.

The primary objectives of Part 1 are to assess the safety and tolerability, and to define the maximum tolerated dose (MTD) of neratinib in combination with capecitabine in subjects with advanced solid tumors.

The primary objective of Part 2 of this study is to confirm the MTD determined in Part 1.

The secondary objective of Part 1 is to collect information on preliminary anti-tumor activity of the combination of neratinib and capecitabine.

Secondary objectives for Part 2 are to collect pharmacokinetic information and to obtain additional efficacy data, such as Objective Response Rate, for subjects with erbB-2 positive breast cancer treated at the MTD of neratinib + capecitabine.


Eligibility criteria: INCLUSION CRITERIA

PART 1:

* confirmed pathologic diagnosis of a solid tumor not curable with available therapies for which neratinib plus capecitabine is a reasonable treatment option.

PART 2:

* confirmed histologically and/or cytologically confirmed diagnosis of breast cancer, metastatic or locally advanced.
* erbB-2 gene amplified tumor (FISH or CISH) or erbB-2 overexpression (IHC 3+, or IHC2+ with FISH or CISH confirmation), based on local testing, or based on centralized FISH testing prior to day 1.
* disease progression on or following at least 1 prior trastuzumab containing treatment regimen (at least 6 weeks) for metastatic or locally advanced disease. (Prior adjuvant trastuzumab is allowed but not required). A 2 week period is required between the last dose of trastuzumab treatment and first dose of the test article.
* Prior treatment with a taxane in the neoadjuvant, adjuvant, locally advanced, and/or metastatic disease treatment setting.

PARTS 1 and 2:

* At least 1 measurable lesion as defined by RECIST criteria.
* LVEF within institutional range of normal as measured by multi-gated acquisition (MUGA) or echocardiogram (ECHO).

EXCLUSION CRITERIA

PART 2:

* prior treatment with capecitabine, lapatinib (20 subjects with prior lapatinib exposure will be enrolled) or any erbB-2 targeted agents except trastuzumab. Treatment with erbB-2 targeted therapy must exceed 2 weeks (14 days) in order to be exclusionary.
* prior treatment with anthracyclines with a cumulative dose of doxorubicin of greater than 400 mg/m², epirubicin dose of greater than 800 mg/m², or the equivalent dose for other anthracyclines.

PARTS 1 and 2:

* Subjects with bone as the only site of disease.
* Active uncontrolled or symptomatic central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Subjects with a history of CNS metastases or cord compression are allowable if they have been considered definitively treated and are off anticonvulsants and steroids for at least 4 weeks before the first dose of test article.
* Any other cancer within 5 years prior to screening with the exception of adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin.

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities
timeFrame: From first dose date to day 21
measure: Maximum Tolerated Dose (MTD) of Neratinib
timeFrame: From first dose date to day 21.
measure: Maximum Tolerated Dose (MTD) of Capecitabine
timeFrame: From first dose date to day 21.
Secondary outcomes:
measure: Overall Response Rate
timeFrame: From first dose date to progression or last tumor assessment, up to three years.
measure: Clinical Benefit Rate
timeFrame: From first dose date to progression or last tumor assessment, up to three years.
measure: Duration of Response
timeFrame: From start date of response to first PD/death, up to three years.
Other outcomes:
Locations:
city: Mobile
country: United States
facility: USA Mitchell Cancer Institute
state: Alabama
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute
state: Florida
city: Post Falls
country: United States
facility: Kootenai Cancer Center
state: Idaho
city: Lafayette
country: United States
facility: The Care Group, LLC. dba Horizon Oncology Center
state: Indiana
city: Saint Louis
country: United States
facility: Washington University School of Medicine Siteman Cancer Center
state: Missouri
city: Lake Success
country: United States
facility: Arena Oncology Associates, PC
state: New York
city: Dayton
country: United States
facility: Dayton Clinical Oncology Program
state: Ohio
city: West Reading
country: United States
facility: Berks Hematology Oncology
state: Pennsylvania
city: Richardson
country: United States
facility: HOPE Oncology
state: Texas
city: San Antonio
country: United States
facility: Cancer Therapy and Research Center at The UT Health Science Center Institute for Drug Development
state: Texas
city: South Brisbane
country: Australia
facility: Mater Private Centre for HOCA
state: Queensland
city: Wodonga
country: Australia
facility: Border Medical Oncology
state: Victoria
city: Ijui
country: Brazil
facility: Associacao Hospital de Caridade Ijui
state: RS - Brazil
city: Porto Alegre
country: Brazil
facility: Associacao Hospitalar Moinhos de Vento Instituto de Edicacao e Pesquisa
state: RS
city: Beijing
country: China
facility: Cancer Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital of Chinese Academy of Medical Sciences
state: Beijing
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
city: Beijing
country: China
facility: The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army
city: Zagreb
country: Croatia
facility: University Hospital Center Zagreb Department of Oncology
city: Hong Kong
country: Hong Kong
facility: UNIMED Medical Institute, Comprehensive Centre for Breast Diseases
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet "B" Belgyogyaszati osztaly
city: Nyiregyhaza
country: Hungary
facility: Josa Andras Oktatokorhaz / Onkoradiologiai Osztaly
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System-Severance Hospital, Yonsei University College of Medicine
city: Seoul
country: Korea, Republic of
facility: Department of Hematology/Oncology, Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center Department of Medicine Division of Oncology
city: Kazan
country: Russian Federation
facility: Republican Clinical Oncology Dispensary
city: Perm
country: Russian Federation
facility: GUZ Perm Regional Oncology Dispensary
city: Saint Petersburg
country: Russian Federation
facility: Leningrad Regional Oncology Dispensary
city: Saint Petersburg
country: Russian Federation
facility: GUZ City Clinical Oncology Dispensary
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburg State Medical University n.a. acad. I.P. Pavlov, Laboratory of Thoracic Oncology of Pulmonology Research Institute
city: Singapore
country: Singapore
facility: Johns Hopkins Singapore International Medical Centre
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
Study officials:
affiliation: Biotechnology
name: Puma
role: STUDY_DIRECTOR
References:
citation: Saura C, Garcia-Saenz JA, Xu B, Harb W, Moroose R, Pluard T, Cortes J, Kiger C, Germa C, Wang K, Martin M, Baselga J, Kim SB. Safety and efficacy of neratinib in combination with capecitabine in patients with metastatic human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2014 Nov 10;32(32):3626-33. doi: 10.1200/JCO.2014.56.3809. Epub 2014 Oct 6.