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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Puma Biotechnology, Inc.
ClinicalTrials.gov Identifier:
NCT00706030
First received: June 25, 2008
Last updated: February 19, 2014
Last verified: February 2014
  Purpose

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 (Tykerb®), 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 (Tykerb®) exposure are also planned to be enrolled in part 2 for exploratory analyses.


Condition Intervention Phase
Breast Cancer
Advanced Malignant Solid Tumors
Drug: neratinib
Drug: vinorelbine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Safety of the combination of neratinib with vinorelbine. [ Time Frame: continuous ] [ Designated as safety issue: Yes ]
  • Overall Response Rate (ORR) in subjects without prior lapatinib exposure. [ Time Frame: every 6 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinical benefit (Complete Response [CR]+Partial Response [PR]+ Stable Disease [SD] > 24 weeks) for subjects without prior lapatinib exposure. [ Time Frame: every 6 weeks ] [ Designated as safety issue: No ]
  • Progression-Free Survival [PFS] rate for subjects without prior lapatinib exposure. [ Time Frame: every 6 weeks ] [ Designated as safety issue: No ]
  • Duration of response for subjects without prior lapatinib exposure. [ Time Frame: every 6 weeks ] [ Designated as safety issue: No ]

Enrollment: 92
Study Start Date: April 2008
Estimated Study Completion Date: December 2014
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
neratinib 240mg daily plus vinorelbine 25 mg/m2 on day 1 and day 8 of a 21 days cycle.
Drug: neratinib
Neratinib 240mg daily
Other Name: HKI-272
Drug: vinorelbine
vinorelbine 25 mg/m2 on day 1 and day 8 of a 21 days cycle.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
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).
  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 ClinicalTrials.gov identifier: NCT00706030

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

No publications provided by Puma Biotechnology, Inc.

Additional 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
Study First Received: June 25, 2008
Last Updated: February 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Puma Biotechnology, Inc.:
Metastatic breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Vinorelbine
Vinblastine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014