We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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.
August 22, 2008
August 26, 2008
August 10, 2017
November 9, 2017
November 9, 2017
December 2008
November 2010   (Final data collection date for primary outcome measure)
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.

Independent radiology review [ Time Frame: Not specified; until documented Progression of Disease ]
Complete list of historical versions of study NCT00741260 on ClinicalTrials.gov Archive Site
  • 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.
Dose Limiting Toxicities [ Time Frame: Pharmacokinetics and site-reported efficacy ]
Not Provided
Not Provided
 
Study Evaluating The Combination Of Neratinib And Capecitabine In Solid Tumors And Breast Cancer
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

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.

Not Provided
Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Breast Cancer
  • 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 Level 1)
    Neratinib 160 mg and Capecitabine 1500 mg/m^2
    Interventions:
    • Drug: Neratinib
    • Drug: Capecitabine
  • Experimental: Neratinib and Capecitabine (Dose Group 2)
    Neratinib 240 mg and Capecitabine 1500 mg/m^2
    Interventions:
    • Drug: Neratinib
    • Drug: Capecitabine
  • Experimental: Neratinib and Capecitabine (Dose Group 3)
    Neratinib 240 mg and Capecitabine 2000 mg/m^2
    Interventions:
    • Drug: Neratinib
    • Drug: Capecitabine
  • Experimental: Neratinib and Capecitabine (Dose Group 4)
    Neratinib 200 mg and Capecitabine 2000 mg/m^2
    Interventions:
    • Drug: Neratinib
    • Drug: Capecitabine
  • Experimental: Neratinib and Capecitabine (Dose Group 5)
    Neratinib 160 mg and Capecitabine 2000 mg/m^2
    Interventions:
    • Drug: Neratinib
    • Drug: Capecitabine
  • Experimental: Neratinib and Capecitabine MTD (Dose Group 6)
    Neratinib and Capecitabine Maximum Tolerated Dose without prior lapatinib
    Interventions:
    • Drug: Neratinib
    • Drug: Capecitabine
  • Experimental: Neratinib and Capecitabine MTD (Dose Group 7)
    Neratinib and Capecitabine Maximum Tolerated Dose with prior lapatinib
    Interventions:
    • Drug: Neratinib
    • Drug: Capecitabine
Saura C, Garcia-Saenz JA, Xu B, Harb W, Moroose R, Pluard T, Cortés 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
105
December 2018
November 2010   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Brazil,   China,   Croatia,   Hong Kong,   Hungary,   Korea, Republic of,   Russian Federation,   Singapore,   Spain,   United States
Argentina
 
NCT00741260
3144A1-2206
B1891017
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
Puma Biotechnology, Inc.
Puma Biotechnology, Inc.
Not Provided
Study Director: Puma Biotechnology
Puma Biotechnology, Inc.
October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP