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

• Status: Terminated
• Trial end date: 2012-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This research is being done to find out how safe and how well the combination of lapatinib and vorinostat works against advanced cancers.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Maryland; University of Maryland, Baltimore
• Collaborator: University of Maryland Greenebaum Cancer Center
• Treatments: Lapatinib; Vorinostat

Criteria

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.