A phase II study for adults with extensive-stage small cell lung cancer is testing the hypomethylating agent guadecitabine combined with the platinum-based chemotherapy drug carboplatin. The study is open to accrual at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center in Indianapolis, Ind.; IU Health Ball Memorial Cancer Center in Muncie, Ind.; and the University of Virginia Cancer Center in Charlottesville, Va.

More than 234,000 new cases of lung and bronchus cancer were estimated for 2018, 10 to 15 percent of which are small cell lung cancer. Small cell lung cancer is often treated with chemotherapy, which could be a platinum-based drug or another form of chemotherapy. However, eventually patients’ cancers stop responding to these drugs.

The HCRN study, LUN17-302, “A Phase II Study Evaluating Efficacy and Safety of Hypomethylating Agent Guadecitabine in Combination with Carboplatin in Extensive Stage Small Cell Lung Cancer,” will help determine whether the combination of guadecitabine with carboplatin is better, the same, or worse than the standard treatment and will evaluate the good and bad effects of this combined therapy.

“In this study we are treating patients with platinum, but combining it with guadecitabine, the drug that hypomethylates DNA, and assessing whether we are potentially able to make the cancer sensitive again to platinum,” said Shadia Jalal, MD, sponsor-investigator of the study and a medical oncologist and researcher at the IU Simon Comprehensive Cancer Center. “The primary goal of the trial is to assess what we call progression-free survival, meaning how long you can live without cancer progressing. We also assess overall survival.”

Cancer cells are sometimes resistant to cancer drugs, and researchers hope to learn whether this combined treatment will help patients with small cell lung cancer overcome resistance to platinum-based chemotherapy.

Cells can turn genes off to hide from the immune system in a process called methylation. This change to the surface of the gene camouflages the gene so it becomes unrecognizable.

“If you over-methylate a gene, then you silence it,” Dr. Jalal said. “Unfortunately, some of those genes that are getting silenced in cancer are genes that are called tumor suppressor genes. If you silence a gene that is supposed to suppress a tumor, you lose the ability to suppress cancer. Guadecitabine does the opposite. It hypomethylates the DNA and through that, you’re basically activating genes that shouldn’t be silenced.”

In this study, researchers are intentionally beginning with guadecitabine and then giving the platinum-based chemotherapy. “Our theory is that some of those agents make you open up your DNA and then you get more platinum lesions on the DNA, and that might be one of the reasons why you respond better,” Dr. Jalal said.

When a patient’s DNA is more open, she added, the platinum has better access to the DNA of the cancer.

Guadecitabine is being tested in clinical trials for the treatment of solid tumors, but it has not been approved by the U.S. Food and Drug Administration (FDA) to treat any disease. Carboplatin is used to treat several types of cancer, including lung cancer. The combination of guadecitabine and carboplatin to treat small cell lung cancer is not FDA-approved and should be considered investigational.

Study participants will receive four treatment cycles, with each cycle lasting 28 days. Guadecitabine will be given as a subcutaneous injection on days 1-5 of each cycle and carboplatin will be given intravenously on day 5 of each cycle. Participants may withdraw from the study at any time in consultation with their doctor if side effects become too severe or their cancer worsens.

Researchers will also collect blood and tissue samples for correlative research. Information gained through correlative tests may help researchers understand why some patients respond differently to treatment than others. These tests will also be used to explore relationships between biomarkers and clinical outcomes.

Up to 34 people may participate in the study. To qualify, participants must be adults age 18 or older with extensive-stage small cell lung cancer.

This study is supported by Astex Pharmaceuticals, Inc.

For more information about this research study, including full eligibility requirements, visit www.clinicaltrials.gov (study #NCT03913455).

About Hoosier Cancer Research Network:

Hoosier Cancer Research Network (formerly known as Hoosier Oncology Group) conducts innovative cancer research in collaboration with academic and community physicians and scientists across the United States. The organization provides comprehensive clinical trial management and support, from conception through publication. Created in 1984 as a program of the Walther Cancer Institute, Hoosier Cancer Research Network became an independent nonprofit clinical research organization in 2007. Since its founding, Hoosier Cancer Research Network has conducted more than 210 trials in a variety of cancer types and supportive care, resulting in more than 350 publications. More than 8,500 subjects have participated in Hoosier Cancer Research Network clinical trials.