Dr Heldermon on a Phase 1/2 Trial Design of Epidiferphane Plus a Taxane in Breast Cancer

“We’re doing [a pharmacokinetics] analysis 1 hour, 2 hours, and 12 hours post-chemotherapy and looking at circulating cytokines that are associated with neuropathy as well as other immune responses, just to make sure that we are not adversely affecting the pharmacokinetics of the chemotherapy itself.”

Coy Heldermon, MD, PhD, associate professor of medicine and breast cancer specialist, Division of Hematology and Oncology, University of Florida, discusses the study design of a phase 1/2 trial (NCT05074290) evaluating the pharmacokinetics and safety of epidiferphane given with taxane chemotherapy in patients with breast cancer.

Although the breast cancer treatment paradigm has grown significantly in recent years, taxane chemotherapy remains a common treatment option. However, adverse effects (AEs) frequently associated with taxanes include anemia and peripheral neuropathy, which are often not addressed well during treatment. Unaddressed AEs during treatment typically lead to treatment dose reductions and delays, and early discontinuation.

In the study, patients with breast cancer started at half of the target taxane dose before receiving the full target dose, Heldermon begins. Patients were stratified based on the type of taxane, which included treatment of 4 tablets of paclitaxel or docetaxel 3 times a day, he explains. A pharmacokinetics analysis was done 1 hour, 2 hours, and 12 hours following chemotherapy, he adds. The safety aspect of the trial included evaluating for circulating cytokines associated with neuropathy and other immune responses to ensure epidiferphane does not negatively affect the pharmacokinetics of the chemotherapy, Heldermon emphasizes.

Of note, the study is including patients at least 18 years of age who are about to begin a new paclitaxel-containing regimen weekly (80-90 mg/m2), a docetaxel-containing regimen every 3 weeks (75-100 mg/m2), or nab-paclitaxel (Abraxane) weekly or every 3 weeks (weekly, 75-125 mg/m2; 3 weeks, 260 mg/m2). Patients could have an ECOG performance status of 0 to 3. Patients on the phase 1 portion of the study required an initiation of neoadjuvant chemotherapy or had a clinical diagnosis of metastatic breast cancer. Patients on the phase 2 portion of the study will be required to have a clinical diagnosis of breast cancer of any stage and histology.

If the safety of epidiferphane and taxanes is established in patients receiving neoadjuvant treatment and in those with metastatic breast cancer, the study will expand the specific cohort that demonstrates safety with taxanes at the target dose, Heldermon notes. This expanded portion of the trial will evaluate safety, effects on tumor response, dose intensity, and—specifically—rates of anemia and neuropathy, he concludes.