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

Puma Biotechnology

Status and phase: Completed; Phase 2; Phase 1

Conditions: Breast Cancer; Advanced Malignant Solid Tumors

Treatments: Drug: neratinib; Drug: vinorelbine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00706030

3144A1-2204 / B1891015

Details and patient eligibility

About

The purpose of this study is 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.

Enrollment: 92 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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92 participants in 4 patient groups

neratinib 160 mg + vinorelbine

Experimental group

Description:

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

Treatment:

Drug: neratinib

Drug: vinorelbine

neratinib 240 mg + vinorelbine

Experimental group

Description:

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

Treatment:

Drug: neratinib

Drug: vinorelbine

neratinib 240 mg + vinorelbine, No Prior Lapatinib

Experimental group

Description:

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

Treatment:

Drug: neratinib

Drug: vinorelbine

neratinib 240 mg + vinorelbine, Prior Lapatinib

Experimental group

Description:

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

Treatment:

Drug: neratinib

Drug: vinorelbine