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Study Evaluating Neratinib (HKI-272) In Combination With Vinorelbine In Subjects With Solid Tumors And Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT00706030
Recruitment Status : Active, not recruiting
First Posted : June 27, 2008
Results First Posted : May 8, 2018
Last Update Posted : May 8, 2018
Sponsor:
Information provided by (Responsible Party):
Puma Biotechnology, Inc.

Brief Summary:

The purposes of this study are to identify the highest tolerable dose of neratinib (HKI-272) in combination with vinorelbine and to assess the safety of the combination of the two drugs as well as to obtain preliminary information on whether the combination of the two drugs has any effect on solid tumors.

The study will be conducted in two parts. In the first part, testing will be done on up to 12 subjects to determine the highest tolerable dose of HKI-272 and vinorelbine in patients with advanced solid tumors. In the second part of the study, approximately 60 additional subjects with metastatic ErbB-2-positive breast cancer, with no prior exposure to lapatinib, are planned to be added to better define the tolerability and preliminary activity of HKI-272 in combination with vinorelbine. Up to 20 additional subjects with ErbB-2-positive breast cancer with prior lapatinib exposure are also planned to be enrolled in part 2 for exploratory analyses.


Condition or disease Intervention/treatment Phase
Breast Cancer Advanced Malignant Solid Tumors Drug: neratinib Drug: vinorelbine Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 92 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study Of HKI-272 In Combination With Vinorelbine In Subjects With Solid Tumors And Metastatic Breast Cancer
Actual Study Start Date : April 2008
Actual Primary Completion Date : October 2009
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: neratinib 160 mg + vinorelbine
neratinib 160 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle
Drug: neratinib
Other Names:
  • HKI-272
  • Nerlynx
Drug: vinorelbine
Experimental: neratinib 240 mg + vinorelbine
neratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle
Drug: neratinib
Other Names:
  • HKI-272
  • Nerlynx
Drug: vinorelbine
Experimental: neratinib 240 mg + vinorelbine, No Prior Lapatinib
neratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle
Drug: neratinib
Other Names:
  • HKI-272
  • Nerlynx
Drug: vinorelbine
Experimental: neratinib 240 mg + vinorelbine, Prior Lapatinib
neratinib 240 mg tablets administered daily by mouth, vinorelbine 25 mg/m^2 administered IV on day 1 and day 8 of 21 day cycle
Drug: neratinib
Other Names:
  • HKI-272
  • Nerlynx
Drug: vinorelbine



Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: From first dose date to progression or last tumor assessment, up to four years and six months. ]
    Overall Response Rate (ORR), subjects with CR or PR by independent review in subjects with ErbB-2-positive breast cancer treated at the MTD of neratinib in combination with vinorelbine 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; and Non-PD for non-target lesions, and no new lesions.

  2. Maximum Tolerated Dose [ Time Frame: From Day 1 to Day 21. ]
    Maximum Tolerated Dose (MTD) of Neratinib in combination with vinorelbine in subjects with advanced solid tumors.


Secondary Outcome Measures :
  1. Clinical Benefit Rate [ Time Frame: From first dose date to progression or last tumor assessment, up to four years and six months. ]
    Percentage of participants with partial response (PR) or complete response (CR) or stable disease > 24 weeks by independent assessment for subjects with ErbB-2-positive breast cancer treated at the MTD of neratinib in combination with vinorelbine, 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.

  2. Progression-Free Survival [ Time Frame: From first dose date to progression or death, up to four years and six months. ]
    Number of weeks between the date of the first dose of test article and the first date of disease recurrence or progression, or death due to any cause, was documented, censored at the last evaluation, investigator assessment. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (v1.0), as at least a 20% increase in the sum of the longest diameters (LD) of target lesions, taking as reference the nadir LD, meaning the smallest sum of the LDs recorded since the treatment started; or unequivocal progression of existing nontarget lesions; or the appearance of any new lesions.

  3. Duration Of Response [ Time Frame: From start date of response to first PD/death, up to four years and six months. ]
    Duration of response for subjects who had complete or partial response from first response to disease progression, death or last assessment 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; and Non-PD for non-target lesions, and no new lesions.



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

Inclusion Criteria:

  • Confirmed pathologic diagnosis of a solid tumor that is not curable with available therapies for which HKI-272 plus vinorelbine is a reasonable treatment option (part 1 only) or Confirmed pathologic diagnosis of ErbB-2-positive breast cancer (current stage IV) in female subjects for which vinorelbine plus HKI-272 is a reasonable treatment option (part 2 only).
  • At least 1 prior antineoplastic chemotherapy treatment regimen for metastatic disease and at least 1 prior treatment with a trastuzumab-containing regimen for at least 6 weeks, for metastatic disease or subject relapsing under adjuvant treatment (part 2 only).
  • At least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST).

Exclusion Criteria:

  • More than 2 prior antineoplastic treatment regimens (excluding hormonotherapy) for metastatic disease. Subjects who relapsed under adjuvant treatment shouldn't have received more than one line of chemotherapy for metastatic disease (part 2 only).
  • Prior treatment with vinorelbine for metastatic setting, or prior treatment with any ErbB-2 targeted agents except trastuzumab (part 2 only). Up to 20 subjects with ErbB-2-overexpressing metastatic breast cancer who have been previously exposed to lapatinib but are not refractory to lapatinib may be enrolled in part 2.
  • Prior treatment with anthracyclines with a cumulative dose of doxorubicin of greater than 400 mg/m2, or of epirubicin dose of greater than 800 mg/m2, or the equivalent dose for other anthracyclines or derivatives (part 2 only).

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): NCT00706030


  Show 35 Study Locations
Sponsors and Collaborators
Puma Biotechnology, Inc.
Investigators
Study Director: Puma Biotechnology

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier: NCT00706030     History of Changes
Other Study ID Numbers: 3144A1-2204
B1891015
First Posted: June 27, 2008    Key Record Dates
Results First Posted: May 8, 2018
Last Update Posted: May 8, 2018
Last Verified: April 2018

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

Keywords provided by Puma Biotechnology, Inc.:
Metastatic breast cancer
HKI-272
Neratinib
Nerlynx
PB-272

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Lapatinib
Vinorelbine
Vinblastine
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators