Clinical trial NCT01118975
Conditions: Breast Cancer Neoplasm Metastasis
Keywords: lapatinib ditosylate Zolinza (vorinostat) Cancer Stem Cells
Sponsor: University of Maryland, Baltimore
Start date: 2010-03-01; Completion date: 2012-10-01
Enrollment: 12 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

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

Detailed description:
Lapatinib is an anti-cancer drug that is approved by the Food and Drug Administration (FDA) for the treatment of metastatic HER2-positive breast cancer. HER2 is a protein involved in the growth of some cancer cells. In lab tests and small clinical studies, lapatinib is also found to kill other types of cancer that have another related protein called epidermal growth factor receptor (EGFR). For participants who have other cancers, the use of lapatinib in this study is investigational. This means the drug is not FDA approved for this use.

Vorinostat is only FDA approved for the treatment of cutaneous T cell lymphoma (a type of cancer). Vorinostat is not currently FDA approved for breast cancer or any other type of cancer. The use of vorinostat in this study is investigational.

Cancer cells can travel through the blood stream and spread to other organs. This process is called metastasis. Lab tests and small clinical trials have shown that vorinostat kills some cancer cells and prevents these cancer cells from traveling through the blood stream. These trials have shown that vorinostat improves how well lapatinib kills cancer cells.

Newer studies have also shown that a subset of cells, called "cancer stem cells," can come back, spread, and become resistant to the usual chemotherapy. In laboratory tests, we found that vorinostat and lapatinib can reduce the number of cancer stem cells. We are looking at combining vorinostat and lapatinib in the hope that we can reduce the number of cancer stem cells and cancer cells traveling through the blood stream.

There are two parts to this study.

First part- We want to learn more about the best dose of vorinostat to be given with lapatinib. We want to learn about how much vorinostat and lapatinib goes into the blood during treatment. We also want to learn the side effects (safety) of the combination of vorinostat and lapatinib. All patients will receive the FDA-approved dose of lapatinib. The first group of patients will get a slightly lower dose of vorinostat than is given normally. If the side effects are not too serious, the next group of patients will get the dose of vorinostat that is given normally.

Second part- We will find out how well the combination of vorinostat and lapatinib works in patients with HER2-positive metastatic breast cancer.

Arms: arm 1: lapatinib 1,250 mg continuous daily and escalating doses of vorinistat (200mg run-up, 300mg, and 400mg 4 days on 3 days off) arm 2: lapatinib 1,250 mg continuous daily and vorinostat 400 mg 4 days on 3 days
Interventions: intervention 1: Vorinostat intervention 2: Lapatinib
Intervention descriptions: intervention 1: 300 mg 4 days on then 3 days off

As defined in the protocol, the dose of vorinostat was increased to 400 mg 4 days on then 3 days off in the pilot phase because the adverse event threshold was not met. In the Phase II cohort, the dose of vorinistat was 400 mg 4 days on and 3 days off. intervention 2: 1,250 mg once daily

Protocol documents: