Medical oncologist Dr. Rama Balaraman isn't expecting any miracles from the pleural mesothelioma clinical trial involving nintedanib, the small-molecule enzyme inhibitor.
She is expecting progress.
Balaraman, at Florida Cancer Affiliates in Ocala, is participating in an international, multicenter trial that will expand the use of nintedanib within the U.S., giving patients another weapon in this fight against mesothelioma cancer.
“It is potentially a new way of approaching [this disease], and it's causing a lot of excitement,” Balaraman told Asbestos.com. “We are hopeful.”
Nintedanib, also known by brand name Ofev, already is administered in the U.S. for treatment of idiopathic pulmonary fibrosis. The drug relieves breathing problems by softening the lungs. The U.S. Food and Drug Administration (FDA) approved its use in 2014.
This phase II/III trial evaluates its safety and effectiveness for use alongside chemotherapy agents pemetrexed and cisplatin. Researchers hope it will increase the effectiveness of chemotherapy.
Pleural mesothelioma is a rare and aggressive cancer that starts in the thin membrane surrounding the lungs. It is caused by inhalation of microscopic asbestos fibers that become lodged in that membrane, causing inflammation, scarring and eventually, leading to cancer that can metastasize throughout the thoracic cavity.
A chemotherapy regimen, which works only sporadically and is not sustainable, is the most used standard-of-care treatment. Although therapies have improved in recent years, the typical patient with pleural mesothelioma still has a life expectancy of only 6-21 months after diagnosis.
Oncologists in Europe Already Administer Nintedanib
In Europe, oncologists administer nintedanib with chemotherapy to treat lung cancer, but the FDA has not approved it for that use in the United States. Clinical trial investigators are hoping this study can move nintedanib toward approval for various cancers, including mesothelioma.
“These clinical studies are important. [They're] the only way you can move treatment forward,” Balaraman said. “Sometimes you take baby steps, and sometimes it's a giant baby. You don't know what drug will be a baby step, and what drug will be that giant baby. Often, it's a combination of two baby-step drugs that make the giant baby.”
Boehringer Ingelheim, a German-based pharmaceutical company, produces the drug and steers the mesothelioma clinical trial in 23 different countries.
U.S. locations include San Francisco, Colorado Springs, Houston; Henderson, Nevada, and various satellite sites.
The study is a double-blind and placebo-controlled trial aimed at those with unresectable pleural mesothelioma. Patients with epithelioid and biphasic cell types are eligible for enrollment. The estimated completion date is October 2019.
Previous studies show nintedanib can inhibit tumor cell proliferation and migration, along with obstructing key enzymes that cause tumors to develop new blood vessels. It can block multiple pathways involved in the scarring of lung tissue.
Cancer Centers in US & Europe Testing Nintedanib
There are several ongoing clinical trials involving nintedanib in the U.S. and Europe.
- Karmanos Cancer Institute in Detroit: Researchers are in the midst of a phase II study of nintedanib for patients with recurrent pleural mesothelioma to assess overall survival improvement with the drug for those who finished their chemotherapy regimen.
- University of Michigan Comprehensive Cancer Center in Ann Arbor and the University of California Davis Cancer Center in Sacramento: Both centers will soon begin recruiting patients as part of the Karmanos study.
- Gustave Roussy cancer center in France: Researchers already are recruiting patients for a phase I study of mesothelioma involving nintedanib with pembrolizumab, an immunotherapy drug also known as Keytruda.
“These types of drugs [like nintedanib] have multiple mechanisms of action,” Balarama said. “It's a new way of approaching [mesothelioma] treatment. And there is a lot of excitement about it right now.”