A Phase I/II Study of HKI-272 in Combination With Vinorelbine in Subjects With Solid Tumors and Metastatic Breast Cancer. - HKI 2204
- Conditions
- MedDRA version: 9.1Level: LLTClassification code 10055113Term: Breast cancer metastaticSolid tumors (part 1) and metastatic breast cancer (part 2).
- Registration Number
- EUCTR2007-007885-39-NL
- Lead Sponsor
- Wyeth Research Division of Wyeth Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 95
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 cytotoxic chemotherapy treatment regimen for metastatic disease (part 2 only).
5. At least 1 prior treatment with a trastuzumab-containing regimen for at least 6 weeks, for metastatic disease (part 2 only).
6. erbB-2 gene amplified tumor detected by fluorescence in situ hybridization (FISH) (part 2 only).
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
1. More than 2 prior cytotoxic chemotherapy treatment regimens 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. Bone or skin 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method