Solid tumors (part 1) and metastatic breast cancer (part 2). MedDRA version: 13.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: NERATINIB
Product Code: HKI-272
Pharmaceutical Form: Tablet
Current Sponsor code: WAY-179272-B
Other descriptive name: HKI-272 Maleate
Concentration unit: mg milligram(s)
Concentration t
Sponsors
Wyeth Research Division of Wyeth Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged =18 years. 2. 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). 3. 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). 4. At least 1 prior antineoplasic chemotherapy treatment regimen for metastatic disease or subject relapsing under adjuvant treatment (part 2 only). 5. At least 1 prior treatment with a trastuzumab-containing regimen for at least 6 weeks [receiving no more than 6 weeks (weekly or tri weekly schedule equivalents) for economical reason is acceptable] , for metastatic disease or subject relapsing under adjuvant treatment (part 2 only) [“relapsing under adjuvant treatment” should be understood as patients still taking trastuzumab treatment or being off trastruzumab treatment for a maximal period of 6 months after the last dose of trastuzumab at the time of disease recurrence]. 6. erbB-2 gene amplified tumor detected by fluorescence in situ hybridization (FISH) or chromogenic in situ hybridization (CISH) (part 2 only). Documentation of erbB-2 status by FISH or CISH performed by a local laboratory is accepted. Otherwise, tumor tissue must be available and adequate for centralised FISH testing prior to study day 1. In case of more than 1 result, the status retrieved on the most recent biopsy should be used. 7. At least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST). 8. Eastern Cooperative Oncology Group (ECOG) status of 0 to 2 (not declining within 2 weeks before signing the informed consent form (ICF)). 9. Recovery from all clinically significant AEs related to prior therapies (excluding alopecia). 10. Left ventricular ejection fraction (LVEF) within the study site’s limits of normal. 11. Screening laboratory values within the following parameters: Absolute neutrophil count (ANC): >=1.5×109/L (1500/mm3) Platelet count: >=100×109/L (100,000/mm3) Hemoglobin: >=9.0 g/dL (90 g/L) Serum creatinine: =1.5×upper limit of normal (ULN) Total bilirubin: =1.5×ULN Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): =2.5 × ULN (=5×ULN if liver metastases are present) 12. For women of childbearing potential, a negative urine or serum pregnancy test result before study entry. 13. All subjects who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control for the duration of the study and for 28 days after the last dose of test article. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. More than 2 prior antineoplasic treatment regimens ( excluding hormonotherapy) for metastatic disease. Subjects who relapsed under adjuvant therapy should not have received more than one line of antineoplasic treatment for metastatic disease (part 2 only). 2. 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. 3. Prior treatment with anthracyclines with a cumulative dose of doxorubicin of >400 mg/m2, or of epirubicin dose of >800 mg/m2, or the equivalent dose for other anthracyclines or derivatives (part 2 only). 4. Major surgery, chemotherapy, radical (curative intent) radiotherapy, investigational agents, or other cancer therapy within at least 2 weeks before treatment day 1. 5. Subjects with bone only disease or skin lesions that are not measurable by CT or MRI as the only site of disease. 6. Subject with history of inflammatory breast cancer 7. Active central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth. 8. QT (QTc) interval >0.47 second or known history of QTc prolongation or torsades de pointes (TdP). 9. Presence of clinically significant or uncontrolled cardiac disease, including congestive heart failure (New York Heart Association [NYHA] functional classification of =2), angina requiring treatment, myocardial infarction within the past 12 months, or any clinically significant supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention. 10. Pregnant or breastfeeding women. 11. Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom (eg, Crohn disease, malabsorption, or grade >=2 diarrhea of any etiology at baseline). 12. Inability or unwillingness to swallow tablets (HKI-272). 13. Preexisting grade 2 or greater motor or sensory neuropathy. 14. Subject known to be human immunodeficiency virus (HIV) seropositive and/or acute chronic hepatitis B (HBsAg positive) or hepatitis C (anti-HCV positive). 15. History of known hypersensitivity to vinorelbine and any of its components. 16. Any other cancer within 5 years prior to screening with the exception of contralateral breast carcinoma, adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin. 17. Clinically significant ongoing or recent infection within 2 weeks before treatment day 1. 18. Evidence of significant medical illness or abnormal laboratory finding that would, in the investigator’s judgment, make the subject inappropriate for this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: The primary objectives of part 1 of the study are to assess the safety and tolerability and to define the maximum tolerated dose (MTD) of HKI-272 in combination with vinorelbine in subjects with advanced solid tumors. Part 2: The primary objective of part 2 of the study is to estimate the ORR for subjects with ErbB-2-positive breast cancer treated at the MTD of HKI-272 in combination with vinorelbine.;Secondary Objective: Part 1: The secondary objectives of part 1 are to obtain preliminary data describing antitumor activity for the combination of HKI-272 with vinorelbine. Part 2: The secondary objectives of part 2 are to confirm the MTD identified in part 1 of the study, to obtain safety and PK information, and to assess additional efficacy parameters including clinical benefit (complete response [CR]+partial response [PR]+stable disease [SD] >=24 weeks), PFS rate, and duration of response to HKI-272 in combination with vinorelbine.;Primary end point(s): The primary end-point of this study is to assess the safety and define the maximum tolerated dose of the combination of HKI-272 with vinorelbine in subjects with solid tumors, and to assess the efficacy of the optimal safe dose for the drug combination in subjects with metastatic breast cancer | — |
Countries
Belgium, France, Netherlands, Poland, Sweden, United Kingdom
Outcome results
None listed