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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00741260
First Posted: August 26, 2008
Last Update Posted: November 9, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Puma Biotechnology, Inc.
  Purpose

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.


Condition Intervention Phase
Breast Cancer Drug: Neratinib Drug: Capecitabine Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Puma Biotechnology, Inc.:

Primary Outcome Measures:
  • Number of Participants With Dose Limiting Toxicities [ Time Frame: From first dose date to 21st day or to time receiving 75% of planned doses ]

    Number of participants reporting Adverse Events Causing Dose Limiting Toxicities (DLT).

    Maximum Tolerated Dose (MTD) reflects the highest dose of Neratinib that did not cause a selected Grade 3 toxicity in >= 2 participants.



Secondary Outcome Measures:
  • Overall Response Rate [ Time Frame: From first dose date to progression or last tumor assessment, up to three years. ]
    Number of Subjects with Complete or Partial Response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.0: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; and Non-PD for non-target lesions, and no new lesions.

  • Clinical Benefit Rate [ Time Frame: From first dose date to progression or last tumor assessment, up to three years. ]
    The percentage of subjects with Complete Response, Partial Response, or Stable Disease at least 24 weeks per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

  • Duration of Response [ Time Frame: From start date of response to first PD/death, up to three years. ]
    Duration of response was measured from the time at which response criteria were met for complete response (CR) or partial response (PR) (whichever status was recorded first) until the first date of recurrence or progressive disease (PD) or death per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.0: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.


Enrollment: 105
Study Start Date: December 2008
Estimated Study Completion Date: December 2018
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Neratinib and Capecitabine (Dose Level 1)
Neratinib 160 mg and Capecitabine 1500 mg/m^2
Drug: Neratinib
Neratinib orally once daily continually
Other Name: HKI-272
Drug: Capecitabine
Capecitabine orally on days 1-14 of each 21 day cycle
Other Name: Xeloda
Experimental: Neratinib and Capecitabine (Dose Group 2)
Neratinib 240 mg and Capecitabine 1500 mg/m^2
Drug: Neratinib
Neratinib orally once daily continually
Other Name: HKI-272
Drug: Capecitabine
Capecitabine orally on days 1-14 of each 21 day cycle
Other Name: Xeloda
Experimental: Neratinib and Capecitabine (Dose Group 3)
Neratinib 240 mg and Capecitabine 2000 mg/m^2
Drug: Neratinib
Neratinib orally once daily continually
Other Name: HKI-272
Drug: Capecitabine
Capecitabine orally on days 1-14 of each 21 day cycle
Other Name: Xeloda
Experimental: Neratinib and Capecitabine (Dose Group 4)
Neratinib 200 mg and Capecitabine 2000 mg/m^2
Drug: Neratinib
Neratinib orally once daily continually
Other Name: HKI-272
Drug: Capecitabine
Capecitabine orally on days 1-14 of each 21 day cycle
Other Name: Xeloda
Experimental: Neratinib and Capecitabine (Dose Group 5)
Neratinib 160 mg and Capecitabine 2000 mg/m^2
Drug: Neratinib
Neratinib orally once daily continually
Other Name: HKI-272
Drug: Capecitabine
Capecitabine orally on days 1-14 of each 21 day cycle
Other Name: Xeloda
Experimental: Neratinib and Capecitabine MTD (Dose Group 6)
Neratinib and Capecitabine Maximum Tolerated Dose without prior lapatinib
Drug: Neratinib
Neratinib orally once daily continually
Other Name: HKI-272
Drug: Capecitabine
Capecitabine orally on days 1-14 of each 21 day cycle
Other Name: Xeloda
Experimental: Neratinib and Capecitabine MTD (Dose Group 7)
Neratinib and Capecitabine Maximum Tolerated Dose with prior lapatinib
Drug: Neratinib
Neratinib orally once daily continually
Other Name: HKI-272
Drug: Capecitabine
Capecitabine orally on days 1-14 of each 21 day cycle
Other Name: Xeloda

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00741260


  Hide Study Locations
Locations
United States, Alabama
USA Mitchell Cancer Institute
Mobile, Alabama, United States, 36604
United States, California
Pacific Shores Medical Group
Long Beach, California, United States, 90813
University of Southern California
Los Angeles, California, United States, 90033
United States, Florida
Florida Hospital Cancer Institute
Orlando, Florida, United States, 32804
United States, Idaho
Kootenai Cancer Center
Post Falls, Idaho, United States, 83854
United States, Indiana
The Care Group, LLC. dba Horizon Oncology Center
Lafayette, Indiana, United States, 47905
United States, Missouri
Washington University School of Medicine Siteman Cancer Center
Saint Louis, Missouri, United States, 63110
United States, New York
Arena Oncology Associates, PC
Lake Success, New York, United States, 11042
United States, Ohio
Dayton Clinical Oncology Program
Dayton, Ohio, United States, 45420
United States, Pennsylvania
Berks Hematology Oncology
West Reading, Pennsylvania, United States, 19611
United States, Texas
HOPE Oncology
Richardson, Texas, United States, 75080
Cancer Therapy and Research Center at The UT Health Science Center Institute for Drug Development
San Antonio, Texas, United States, 78229
Australia, Queensland
Mater Private Centre for HOCA
South Brisbane, Queensland, Australia, 4101
Australia, Victoria
Border Medical Oncology
Wodonga, Victoria, Australia, 3690
Brazil
Associacao Hospital de Caridade Ijui
Ijui, RS - Brazil, Brazil, 98700-000
Associacao Hospitalar Moinhos de Vento Instituto de Edicacao e Pesquisa
Porto Alegre, RS, Brazil, 90035-001
China, Beijing
Cancer Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing, China, 100021
Peking Union Medical College Hospital of Chinese Academy of Medical Sciences
Beijing, Beijing, China, 100032
China, Jiangsu
Jiangsu Cancer Hospital
Nanjing, Jiangsu, China, 210009
China
The Hospital Affiliated Academy Military Medical Science, Chinese People's Liberation Army
Beijing, China, 100071
Croatia
University Hospital Center Zagreb Department of Oncology
Zagreb, Croatia, 10000
Hong Kong
UNIMED Medical Institute, Comprehensive Centre for Breast Diseases
Hong Kong, Hong Kong
Hungary
Orszagos Onkologiai Intezet "B" Belgyogyaszati osztaly
Budapest, Hungary, 1122
Josa Andras Oktatokorhaz / Onkoradiologiai Osztaly
Nyiregyhaza, Hungary, 4400
Korea, Republic of
Yonsei University Health System-Severance Hospital, Yonsei University College of Medicine
Seoul, Korea, Republic of, 120-752
Department of Hematology/Oncology, Samsung Medical Center
Seoul, Korea, Republic of, 135-710
Asan Medical Center Department of Medicine Division of Oncology
Seoul, Korea, Republic of, 138-736
Russian Federation
Republican Clinical Oncology Dispensary
Kazan, Russian Federation, 420029
GUZ Perm Regional Oncology Dispensary
Perm, Russian Federation, 614066
Leningrad Regional Oncology Dispensary
Saint Petersburg, Russian Federation, 188663
GUZ City Clinical Oncology Dispensary
Saint Petersburg, Russian Federation, 197022
Saint-Petersburg State Medical University n.a. acad. I.P. Pavlov, Laboratory of Thoracic Oncology of Pulmonology Research Institute
Saint Petersburg, Russian Federation, 197022
Singapore
Johns Hopkins Singapore International Medical Centre
Singapore, Singapore, 308433
Spain
Hospital Vall d'Hebron
Barcelona, Spain, 08035
Hospital Gregorio Maranon
Madrid, Spain, 28007
Hospital Clinico San Carlos
Madrid, Spain, 28040
Hospital Clínico Universitario de Valencia
Valencia, Spain, 46010
Sponsors and Collaborators
Puma Biotechnology, Inc.
Investigators
Study Director: Puma Biotechnology
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier: NCT00741260     History of Changes
Other Study ID Numbers: 3144A1-2206
B1891017
First Submitted: August 22, 2008
First Posted: August 26, 2008
Results First Submitted: August 10, 2017
Results First Posted: November 9, 2017
Last Update Posted: November 9, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Puma Biotechnology, Inc.:
Solid Tumor
erbB2+ Breast Cancer
Prior trastuzumab
Metastatic
Neratinib
HKI-272
Nerlynx
HER2
PB-272

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Capecitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents