This trial is active, not recruiting.

Conditions breast cancer, advanced malignant solid tumors
Treatments neratinib, vinorelbine
Phase phase 1/phase 2
Targets HER2, EGFR
Sponsor Puma Biotechnology, Inc.
Start date April 2008
End date October 2009
Trial size 92 participants
Trial identifier NCT00706030, 3144A1-2204, B1891015


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
neratinib 240mg daily plus vinorelbine 25 mg/m2 on day 1 and day 8 of a 21 days cycle.
neratinib HKI-272
Neratinib 240mg daily
vinorelbine 25 mg/m2 on day 1 and day 8 of a 21 days cycle.

Primary Outcomes

Safety of the combination of neratinib with vinorelbine.
time frame: continuous
Overall Response Rate (ORR) in subjects without prior lapatinib exposure.
time frame: every 6 weeks

Secondary Outcomes

Clinical benefit (Complete Response [CR]+Partial Response [PR]+ Stable Disease [SD] > 24 weeks) for subjects without prior lapatinib exposure.
time frame: every 6 weeks
Progression-Free Survival [PFS] rate for subjects without prior lapatinib exposure.
time frame: every 6 weeks
Duration of response for subjects without prior lapatinib exposure.
time frame: every 6 weeks

Eligibility Criteria

Female participants at least 18 years old.

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).

Additional Information

Official title A Phase 1/2 Study Of HKI-272 In Combination With Vinorelbine In Subjects With Solid Tumors And Metastatic Breast Cancer
Trial information was received from ClinicalTrials.gov and was last updated in June 2016.
Information provided to ClinicalTrials.gov by Puma Biotechnology, Inc..