Solid tumors (part 1) and metastatic breast cancer (part 2) MedDRA version: 9.1 Level: LLT Classification code 10065252 Term: Solid tumor MedDRA version: 9.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer
Conditions
Sponsors
Wyeth Research Division of Wyeth Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and/or surgically sterile or postmenopausal female OR female subjects aged 18 years or older. 2. Subjects enrolled in Part 1 must have confirmed pathologic diagnosis of a solid tumor that is not curable with available therapies for which neratinib plus capecitabine is a reasonable treatment option. 3. Subjects enrolled in Part 2 must have a confirmed pathologic diagnosis of breast cancer, metastatic or locally advanced. 4. Subjects enrolled in Part 2 must have erbB-2 gene amplified tumor. Documentation of erbB-2 status by FISH or erbB-2 overexpression (IHC 3+) based on local testing is accepted. Otherwise, tumor tissue must be available and adequate for centralized FISH testing prior to study day 1. In case of more than one result, the status retrieved on the most recent biopsy should be used. 5. Subjects enrolled in Part 2 must have disease progression following at least 1 prior trastuzumab containing treatment regimen (at least 6 weeks) for metastatic or locally advanced disease. (Prior adjuvant trastuzumab is allowed but not required). 6. Subjects enrolled in Part 2 must have received prior treatment (neoadjuvant, adjuvant, or metastatic) with at least 4 cycles of both a taxane and an anthracycline given sequentially or concurrently (2 cycles of treatment are acceptable if disease progresses during treatment). 7. At least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. 8. Eastern Cooperative Oncology Group (ECOG) status of 0 to 2, not declining within two weeks before informed consent signing. 9. Recovery from all clinically significant adverse effects related to prior therapies (excluding alopecia). 10. Left ventricular ejection fraction (LVEF) within institutional limits of normal. 11. Screening laboratory values within the following parameters: ANC : ?1.5×109/L (1500/mm3) Platelet count: ?75×109/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 child bearing potential, a negative urine or serum pregnancy test result before study entry. A woman of childbearing potential is one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives. 13. All subjects who are biologically capable of having children 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. A subject is biologically capable of having children if he or she is using contraceptives or if his or her sexual partner is sterile or using contraceptives. Oral contraceptives may not be used as the sole form of birth control for this study; oral contraceptives must always be used in conjunction with a second medically approved method of contraception. 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. Subjects enrolled in Part 2 must have received no prior treatment with lapatinib, capecitabine, or any erbB-2 targeted agents except trastuzumab. 2. Subjects enrolled in Part 2 must not have received prior treatment with anthracyclines with a cumulative dose of doxorubicin of > 400 mg/m2, epirubicin dose of >800 mg/m2, or the equivalent dose for other anthracyclines. 3. Major surgery, chemotherapy, radical (curative intent) radiotherapy, any investigational agents, or other cancer therapy within 2 weeks of treatment day 1. 4. Subjects with bone or skin as the only site of disease. 5. Active central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Subjects with a history of CNS metastases or cord compression are allowable if they have been definitively treated, have been clinically stable for at least three months, and off anticonvulsants before first dose of test article (steroids are permitted, provided subject is on stable doses). 6. QTc interval >0.47 second or known history of QTc prolongation or Torsade de Pointes (TdP). 7. 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. 8. Pregnant, or breast-feeding women. 9. Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn?s disease, malabsorption, or Grade?2 diarrhea of any etiology at baseline). 10. Inability or unwillingness to swallow tablets or capsules. 11. Any other cancer within 5 years prior to screening with the exception of adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin 12. Any major medical illness or abnormal laboratory finding that, in the investigator?s judgment, will substantially increase the risk associated with the subject?s participation in and completion of the study. Examples include, but are not limited to, serious active infection (i.e. requiring intravenous antibiotic or antiviral agent), uncontrolled major seizure disorder, significant pulmonary disorder (e.g. interstitial pneumonitis, pulmonary hypertension), or psychiatric disorder that would interfere with subject safety or informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: The primary objectives of Part 1 are to assess the safety and tolerability, and to define the MTD of neratinib in combination with capecitabine in subjects with advanced solid tumors. Part 2: The primary objective of Part 2 of this study is to compare the objective response rate (ORR = CR + PR) for subjects with erbB-2 positive breast cancer treated at the MTD of neratinib + capecitabine vs neratinib monotherapy vs. lapatinib + capecitabine.;Secondary Objective: Part 1: The secondary objective of Part 1 is to obtain preliminary anti-tumor activity for neratinib + capecitabine. Part 2: The secondary objectives of Part 2 are to confirm the MTD identified in Part 1 of the study, obtain safety and PK information, and assess additional efficacy parameters including Progression Free Survival (PFS), Overall Survival (OS), Clinical benefit Rate (CR + PR +SD?24 weeks), and duration of response for each treatment arm.;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 neratinib with capecitabine in subjects with solid tumors, and to compare the objective response rate (ORR = CR + PR) for subjects with erbB-2 positive breast cancer treated at the MTD of neratinib in combination with capecitabine versus neratinib monotherapy versus lapatinib in combination with capecitabine. | — |
Countries
Hungary, Spain
Outcome results
None listed