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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.
Information provided by (Responsible Party):
Puma Biotechnology, Inc. Identifier:
First received: August 22, 2008
Last updated: June 22, 2016
Last verified: June 2016

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: Single Group 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:
  • Investigator assessed radiology review [ Time Frame: until documented Progression of Disease ]

Secondary Outcome Measures:
  • Dose Limiting Toxicities; Pharmacokinetics and site-reported efficacy [ Time Frame: until documented Progression of Disease ]

Enrollment: 105
Study Start Date: December 2008
Estimated Study Completion Date: December 2017
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Neratinib and capecitabine
Drug: Neratinib
Neratinib 240mg, continuous daily
Drug: capecitabine
1500mg/m² of Capecitabine, on days 1-14 of each 21 day cycle.
Other Name: Xeloda


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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.
  • Part 2: 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.
  • Part 2: 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+2: At least 1 measurable lesion as defined by RECIST criteria.
  • Parts 1+2: 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.
  • Part 2: 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+2: Subjects with bone as the only site of disease.
  • Parts 1+2: 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.
  • Parts 1+2: 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
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00741260

  Show 44 Study Locations
Sponsors and Collaborators
Puma Biotechnology, Inc.
Study Director: Puma Biotechnology
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Puma Biotechnology, Inc. Identifier: NCT00741260     History of Changes
Other Study ID Numbers: 3144A1-2206
Study First Received: August 22, 2008
Last Updated: June 22, 2016

Keywords provided by Puma Biotechnology, Inc.:
solid tumor
erbB2+ breast cancer
prior Herceptin

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents processed this record on August 18, 2017