DINOMITE Trial Explores Papaverine Plus Radiation in Rectal Cancer

Terence M. Williams, MD, PhD, a professor and chair in the Department of Radiation Oncology at City of Hope, discusses what inspired the new phase 1 DINOMITE trial (NCT06834126) at City of Hope that aims to treat patients with rectal cancer with papaverine and radiation therapy. He also explains what makes this different from traditional methods.

“The research that we were doing was focused on understanding how to improve the effects of radiation tumor cells while sparing the normal cells that surround the tumor. One of the areas we became interested in was in colorectal cancer,” Williams explains.

According to Williams, rectal cancer is about a third of colorectal cancer. This type of cancer commonly is treated when it is localized in the pelvis area with chemotherapy, radiation and surgery.

“Sometimes surgery is required, or the type of surgery that is required is such that that leaves a patient with a permanent colostomy…and they are forced to have that for the rest of their lives,” says Williams.

Papaverine, an investigational drug shown to sensitise tumor cells to radiation therapy by blocking oxygen consumption in tumor cells in preclinical and ongoing clinical trials, is now being tested in this phase 1 study when given in combination with radiation therapy.

The phase 1 trial will test the combination of papaverine and radiation therapy when given to patients with rectal cancer that has spread to nearby tissue or lymph nodesetermine, aiming to determine the maximum tolerated dose and the recommended phase 2 dose. The other primary end point of the trial is to determine the safety and tolerability of the combination.

“We believe that this strategy is a new way to effectively improve radiation effects on tumors, more so than normal tissues, because normal tissue have well oxygenated already, but tumors have areas of hypoxia, which is low oxygen content. So, this drug is designed to elevate the oxygen levels within tumors,” Williams says.

REFERENCE:

Papaverine in combination with radiation therapy for the treatment of locally advanced rectal cancer, DINOMITE trial. ClinicalTrials.gov. Updated March 24, 2025. Accessed May 28, 2025. https://clinicaltrials.gov/study/NCT06834126