Study Evaluating The Combination Of Neratinib And Capecitabine In Solid Tumors And Breast Cancer

NCT ID: NCT00741260

Last Updated: 2018-09-05

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

105 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-12-09

Study Completion Date

2018-06-30

Brief Summary

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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.

Detailed Description

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Conditions

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Breast Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Neratinib and Capecitabine (Dose Level 1)

Neratinib 160 mg and Capecitabine 1500 mg/m\^2

Group Type EXPERIMENTAL

Neratinib

Intervention Type DRUG

Neratinib orally once daily continually

Capecitabine

Intervention Type DRUG

Capecitabine orally on days 1-14 of each 21 day cycle

Neratinib and Capecitabine (Dose Group 2)

Neratinib 240 mg and Capecitabine 1500 mg/m\^2

Group Type EXPERIMENTAL

Neratinib

Intervention Type DRUG

Neratinib orally once daily continually

Capecitabine

Intervention Type DRUG

Capecitabine orally on days 1-14 of each 21 day cycle

Neratinib and Capecitabine (Dose Group 3)

Neratinib 240 mg and Capecitabine 2000 mg/m\^2

Group Type EXPERIMENTAL

Neratinib

Intervention Type DRUG

Neratinib orally once daily continually

Capecitabine

Intervention Type DRUG

Capecitabine orally on days 1-14 of each 21 day cycle

Neratinib and Capecitabine (Dose Group 4)

Neratinib 200 mg and Capecitabine 2000 mg/m\^2

Group Type EXPERIMENTAL

Neratinib

Intervention Type DRUG

Neratinib orally once daily continually

Capecitabine

Intervention Type DRUG

Capecitabine orally on days 1-14 of each 21 day cycle

Neratinib and Capecitabine (Dose Group 5)

Neratinib 160 mg and Capecitabine 2000 mg/m\^2

Group Type EXPERIMENTAL

Neratinib

Intervention Type DRUG

Neratinib orally once daily continually

Capecitabine

Intervention Type DRUG

Capecitabine orally on days 1-14 of each 21 day cycle

Neratinib and Capecitabine MTD (Dose Group 6)

Neratinib and Capecitabine Maximum Tolerated Dose without prior lapatinib

Group Type EXPERIMENTAL

Neratinib

Intervention Type DRUG

Neratinib orally once daily continually

Capecitabine

Intervention Type DRUG

Capecitabine orally on days 1-14 of each 21 day cycle

Neratinib and Capecitabine MTD (Dose Group 7)

Neratinib and Capecitabine Maximum Tolerated Dose with prior lapatinib

Group Type EXPERIMENTAL

Neratinib

Intervention Type DRUG

Neratinib orally once daily continually

Capecitabine

Intervention Type DRUG

Capecitabine orally on days 1-14 of each 21 day cycle

Interventions

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Neratinib

Neratinib orally once daily continually

Intervention Type DRUG

Capecitabine

Capecitabine orally on days 1-14 of each 21 day cycle

Intervention Type DRUG

Other Intervention Names

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HKI-272 Xeloda

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Puma Biotechnology, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Puma

Role: STUDY_DIRECTOR

Biotechnology

Locations

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USA Mitchell Cancer Institute

Mobile, Alabama, United States

Site Status

Pacific Shores Medical Group

Long Beach, California, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

Florida Hospital Cancer Institute

Orlando, Florida, United States

Site Status

Kootenai Cancer Center

Post Falls, Idaho, United States

Site Status

The Care Group, LLC. dba Horizon Oncology Center

Lafayette, Indiana, United States

Site Status

Washington University School of Medicine Siteman Cancer Center

St Louis, Missouri, United States

Site Status

Arena Oncology Associates, PC

Lake Success, New York, United States

Site Status

Dayton Clinical Oncology Program

Dayton, Ohio, United States

Site Status

Berks Hematology Oncology

West Reading, Pennsylvania, United States

Site Status

HOPE Oncology

Richardson, Texas, United States

Site Status

Cancer Therapy and Research Center at The UT Health Science Center Institute for Drug Development

San Antonio, Texas, United States

Site Status

Mater Private Centre for HOCA

South Brisbane, Queensland, Australia

Site Status

Border Medical Oncology

Wodonga, Victoria, Australia

Site Status

Associacao Hospitalar Moinhos de Vento Instituto de Edicacao e Pesquisa

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Associacao Hospital de Caridade Ijui

Ijuí, RS - Brazil, Brazil

Site Status

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Site Status

Peking Union Medical College Hospital of Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Site Status

Jiangsu Cancer Hospital

Nanjing, Jiangsu, China

Site Status

The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army

Beijing, , China

Site Status

University Hospital Center Zagreb Department of Oncology

Zagreb, , Croatia

Site Status

UNIMED Medical Institute, Comprehensive Centre for Breast Diseases

Hong Kong, , Hong Kong

Site Status

Orszagos Onkologiai Intezet "B" Belgyogyaszati osztaly

Budapest, , Hungary

Site Status

Josa Andras Oktatokorhaz / Onkoradiologiai Osztaly

Nyíregyháza, , Hungary

Site Status

Republican Clinical Oncology Dispensary

Kazan', , Russia

Site Status

GUZ Perm Regional Oncology Dispensary

Perm, , Russia

Site Status

Leningrad Regional Oncology Dispensary

Saint Petersburg, , Russia

Site Status

GUZ City Clinical Oncology Dispensary

Saint Petersburg, , Russia

Site Status

Saint-Petersburg State Medical University n.a. acad. I.P. Pavlov, Laboratory of Thoracic Oncology of Pulmonology Research Institute

Saint Petersburg, , Russia

Site Status

Johns Hopkins Singapore International Medical Centre

Singapore, , Singapore

Site Status

Yonsei University Health System-Severance Hospital, Yonsei University College of Medicine

Seoul, , South Korea

Site Status

Department of Hematology/Oncology, Samsung Medical Center

Seoul, , South Korea

Site Status

Asan Medical Center Department of Medicine Division of Oncology

Seoul, , South Korea

Site Status

Hospital Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Gregorio Maranon

Madrid, , Spain

Site Status

Hospital Clinico San Carlos

Madrid, , Spain

Site Status

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Site Status

Countries

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United States Australia Brazil China Croatia Hong Kong Hungary Russia Singapore South Korea Spain

References

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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.

Reference Type DERIVED
PMID: 25287822 (View on PubMed)

Other Identifiers

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3144A1-2206 / B1891017

Identifier Type: -

Identifier Source: org_study_id

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