Cervical cancer patients are being recruited for a Phase 2 clinical trial of a combination of Keytruda (pembrolizumab) and chemoradiation therapy.
The randomized trial (NCT02635360) is expected to include about 88 adults with locally advanced cervical cancer, or LACC. Keytruda’s developer, Merck, is sponsoring the trial, with University of Virginia researchers conducting it.
Researchers will discuss the trial at the American Society of Clinical Oncology annual meeting in Chicago, June 2-6. The title of the poster presentation is “A randomized phase II study of chemoradiation and pembrolizumab for locally advanced cervical cancer.”
The standard of care treatment for LACC is chemoradiation therapy. This includes a combination of brachytherapy — a form of radiotherapy in which radioactive seeds are implanted inside or close to tumors — and Platinol-based (cisplatin-based) chemotherapy. But only 66 percent of those who take this treatment regimen survive at least five years.
Most cervical cancer cells express DNA from the human papillomavirus, indicating the virus is present in the cells. It is not fully understood why and how this happens. Expression is the process by which information from a gene is used to create a functional product like a protein.
The cancer cells’ expression of DNA virus indicates that immune cells have failed to destroy all viral DNA and prevent its integration in human cells. That integration has been associated with the transformation of normal cervical cells into cancer cells.
Scientists think the transformation also impacts the regulation of proteins like PD-L1, which is believed to play a major role in suppressing the immune system. Problems with the regulation allow cancer cells to prevent immune cells from recognizing and destroying them, scientists believe.
In addition to these complex regulatory mechanisms, most of the immune cells that are able to infiltrate tumors express another protein, PD-1. The binding of the PD-1 and PD-L1 proteins inhibits immune cells from attacking cancer cells, scientists believe.
All this evidence suggests that blocking the signals that inhibit the immune system and enhancing immune response could be an effective strategy against this type of cancer.
The Phase 2 clinical trial was designed to test this hypothesis. By targeting immune-regulation mechanisms after chemoradiation therapy, researchers believe Keytruda can give the immune cell response to the cancer more punch.
While all patients in the trial will receive intravenous Keytruda once every 21 days for three months, they will be randomized so that some receive it at the same time as chemoradiation and others afterward.
In the first arm of the trial, patients will receive standard Platinol chemotherapy weekly, along with brachytherapy in the first five to six weeks. After chemoradiation is complete, patients will receive Keytruda. In the second arm, patients will receive Keytruda at the same time they are receiving chemotherapy and brachytherapy.
The primary goals of the study are to determine the safety of the treatment and the immune system’s response to Keytruda in both treatment regimens tested. Secondary endpoints include patients’ overall survival after treatment; their progression-free survival, or the time it takes before their cancer progresses; how many patients’ cancer spreads to other parts of their body; and patients’ metabolic response, or reaction to the therapy in any part of their body.