Now Enrolling: ComboMATCH treatment trial E4 is testing a new option for patients with advanced solid tumors that progress despite taxane chemotherapy

Chemotherapy treatments are part of the usual approach for adults with advanced solid tumor cancers. Taxanes, which are a type of chemotherapy, have decades of use targeting cancer cells and helping to stop or slow their growth. However, when taxanes are used alone in patients with advanced disease, especially those who have had prior taxane therapy, tumors will continue to grow and spread in about 90% of patients.

One taxane used to treat cancer is paclitaxel—but sometimes proteins in the cancer can block the drug from working. In the EAY191-E4 trial, researchers want to see if another drug, nilotinib, helps paclitaxel work better. Nilotinib is part of a class of medications called kinase inhibitors. It is given in pill form and works by interfering with a protein that signals cancer cells to multiply—essentially blocking the protein from blocking the paclitaxel. This helps slow or stop cancer cells. Nilotinib is FDA-approved to treat adults with certain types of chronic myeloid leukemia (CML).

Pre-clinical studies recently showed that nilotinib and paclitaxel may be stronger and more effective together at killing cancer cells than either drug alone. A small phase 1 clinical trial (NCT02379416), which is ongoing, is testing the safety of the combination. It is demonstrating efficacy with the nilotinib-paclitaxel combination, including in patients who did not benefit from prior taxane-based therapy.

Surprisingly, both this trial and the pre-clinical data found less nerve damage in hands and feet (peripheral neuropathy) from the combination compared to paclitaxel alone. Peripheral neuropathy is a common and painful side effect of paclitaxel.

Based on these discoveries, researchers have opened the EAY191-E4 trial to evaluate the nilotinib-paclitaxel combination in 40 patients. Further, as they collect information on the side effects of the treatment, they hope to determine whether nilotinib may help make paclitaxel less toxic and more tolerable for patients. If this trial is successful, the combination would move on to a larger randomized phase 3 trial for confirmation outside of ComboMATCH.

To be eligible for EAY191-E4, patients must have solid cancers that are progressing after treatment with taxane therapies. They must not have a mutation in the c-KIT or PDGFRA tumor genes.

All patients will receive nilotinib and paclitaxel together in cycles that will repeat every 28 days. Patients may stay on treatment so long as the tumors shrink or remain stable, and they are able to tolerate any side effects. Patients will have imaging (CT scans or MRI) before, during, and after treatment to measure tumor size and thus monitor which tumors respond to—or resist—the combination treatment.

Another goal of the trial is to gather information for future research. To that end, patients will undergo a tumor biopsy and submit blood samples before starting treatment. Blood samples are being collected to look for the presence of circulating tumor DNA.

To take part in this treatment trial, patients must first enroll in the ComboMATCH registration trial (EAY191) to help determine eligibility.

This treatment trial is led by Alice Chen, MD, of the National Cancer Institute.

Learn more about EAY191-E4 at ecog-acrin.org.