GCC 0845:Vorinostat and Lapatinib in Advanced Solid Tumors and Advanced Breast Cancer to Evaluate Response and Biomarkers

This is an interventional treatment trial for Breast Cancer focused on measuring lapatinib ditosylate, Zolinza (vorinostat), Cancer Stem Cells Read More

Inclusion Criteria:

• Age greater than or equal to 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
• Consent for peripheral blood sampling for analysis of circulating tumor cells.
• Patients must have adequate organ and marrow function as defined by the protocol.
• Female patients with histologically confirmed adenocarcinoma of the breast with recurrent local-regional disease, or metastatic disease that have progressed after treatment with regimens that include an anthracycline, a taxane, or trastuzumab.

• Human Epidermal growth factor Receptor 2 (HER2) positive in the primary or secondary tumor tissue as defined by:

  • Grade 3plus staining intensity (on a scale of 0 to 3) by means of Immunohistochemistry (IHC) analysis OR
  • Gene amplification on fluorescence in situ hybridization (FISH) greater than or equal to 2.2.
• Patients must have measurable disease by the Response Evaluation Criteria In Solid Tumors (RECIST)criteria at the time of enrollment.
• Prior trastuzumab therapy is allowed. Trastuzumab should be stopped at least 4 weeks prior to enrollment.

Exclusion Criteria:

• Patients receiving any other investigational agents.
• Prior exposure to lapatinib, vorinostat, or other Histone deacetylase (HDAC) inhibitors. Prior valproic acid exposure is allowed providing this is a greater than or equal to 30 days wash-out period.
• History of allergic reactions or hypersensitivity to compounds of similar chemical or biologic composition to vorinostat or lapatinib.
• Patients with history of clinically significant or uncontrolled cardiac disease, as defined by the protocol, or any significant cardiac condition that in the judgment of the investigator is unsuitable.
• Significant chronic or recent (less than 30 days) acute gastrointestinal disorder with diarrhea as a major symptom (e.g. Crohn's disease, malabsorption, or Grade 2 or greater diarrhea of any etiology at baseline).
• Prior exposure to more than 360 mg/m2 doxorubicin or liposomal doxorubicin, more than 120 mg/m2 mitoxantrone, or more than 90 mg/m2 idarubicin, or elevated baseline cardiac troponin T (more than upper limit of normal).
• Patients with active Central Nervous System (CNS) metastasis and/or carcinomatous meningitis are excluded. Patients with CNS metastasis who have completed a course of therapy would be eligible for the study provided they are clinically stable for 3 weeks prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis and (2) off steroids and/or anticonvulsants, for at least 4 weeks before an enrollment.
• Female patient that is pregnant or breastfeeding or expecting to conceive during the study. Women able to have children must have a negative pregnancy test prior to enrollment. All patients must use two effective methods of contraception (including a barrier method) during treatment and for 12 weeks after stopping treatment.
• The patient is known to be Human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C-positive (test results are not required in order to participate).
• Patients with current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirement.
• Previous or current systemic malignancy within the past 3 years other than the following: Female- breast cancer or adequately treated carcinoma in-situ of the cervix, or Female and Male- basal/squamous carcinoma of the skin.