Research & Clinical Trials

New Clinical Trial Tests Drug to Control Cancer Stem Cells

Written By:
Oct 23, 2013
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Written By: Tim Povtak,
October 23, 2013

A recently launched, international clinical trial that involves the targeted killing of mesothelioma cancer stem cells soon could provide a much-needed breakthrough for patients around the world.

The mesothelioma trial, which is expected to involve 350-400 patients across 11 countries, will study the cancer stem cell inhibitor defactinib (VS-6063), which has shown considerable promise in treating other cancers.

“The potential is there. If this (trial) turns out positive, it would be a big step forward for mesothelioma patients. It could become the next drug to be used,” oncologist James Stevenson, M.D., principal investigator at the Cleveland Clinic, told “It has been a long time coming. I know all the investigators working on this trial are excited about the promise.”

Stem cells represent only a small percentage of cells in a tumor, but they are considered the major cause of tumor resistance to chemotherapy, the primary reason for recurrence of the cancer, and eventual progression of the disease.

This will be the first time a drug has been designed to inhibit a specific protein  (Focal Adhesion Kinase, or FAK) within the mesothelioma stem cells.

“The hopes are high that we have something very promising here,” said Dean Fennell, Ph.D., Thoracic Medical Oncology chair at the University of Leicester in the United Kingdom.

“There is a lot of enthusiasm for this one. It could change the way we treat this disease,” said Fennell, also the incoming president of the International Mesothelioma Interest Group. “It has that kind of potential.”

Long-Term Maintenance

Defactinib, in the study, will be used for mesothelioma maintenance that follows the standard chemotherapy treatment with Alimta (Pemetrexed). Unlike standard chemotherapy, defactinib is less toxic with considerably fewer side effects, allowing it to be used for extended periods to combat the tumor stem cells that Alimta misses.

Alimta still is the only FDA-approved drug for the treatment of mesothelioma. It was approved in 2005. It has shown little, if any, ability to control cancer stem cells, which made this trial with defactinib so highly anticipated. Past research has suggested that standard chemotherapy, while shrinking the size of tumors, actually increases the percentage of untouchable stem cells, which leads to metastasis.

“The stem cells are like the queen bee in the beehive. They are the rare ones that drive the growth of the cancer,” Fennell told “When these cells are attacked, the cancer does not have the capacity to grow.”

Both Stevenson and Fennell were encouraged by the international scope of this trial and the early enthusiasm by both investigators and potential participants. Defactinib, for mesothelioma treatment, already has received an FDA Orphan Drug designation, which is designed to accelerate the development of therapies for rare diseases.

Study Will Span the Globe

The multi-center study involves the United States, Canada, Australia, the United Kingdom, New Zealand and South Africa. Fennell believes the broad coverage could produce a quicker-than-normal data analysis, coming as early as the end of 2014 or beginning of 2015.

The Cleveland Clinic in Ohio, along with the Abramson Cancer Center in Philadelphia, and the University of Chicago Medical Center in Chicago, are the three sites recruiting patients in the United States.

The study will compare the overall survivor rates and progression-free survival of subjects receiving defactinib against those receiving a placebo. Participants will receive 400 mg orally twice daily, or the placebo.

Participants will be required to first undergo a test to determine their level of the biomarker merlin. The pre-trial data already has suggested that defactinib will be more effective in patients with lower levels of merlin. The study will group patients accordingly, to evaluate the effectiveness of the drug in both the overall mesothelioma population, and also for those with low levels of merlin.

Help Could Be Near

Mesothelioma, which is caused by exposure to asbestos, has no cure. A diagnosis often comes with a prognosis of just six to 18 months. Even with a multi-level approach that includes surgery, chemotherapy and radiation, the increased survival is usually measured in months and not years.

“The incidence of mesothelioma is increasing worldwide. This is not going away,” Fennell said. “There is an unmet need right now for better treatment options. Our hope is to recruit participants quickly.”

Verastem Inc., which developed defactinib, also has helped fund testing the drug in trials involving ovarian cancer and non-small cell lung cancer. Verastem is developing several cancer drugs designed to target stem cells.

“Defactinib is a drug that is unique in the way it works,” Stevenson said. “To find a drug that could control this disease, to kill the stem cells left behind, would be a vast improvement.”

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