A phase II clinical trial of albumin-bound paclitaxel, cisplatin, gemcitabine (NABPLAGEM), and paricalcitol as neoadjuvant therapy in pancreatic cancer

BACKGROUND: For patients with untreated pancreatic ductal adenocarcinoma (PDAC), chemotherapy before surgery ("neoadjuvant therapy") has shown benefit in reducing recurrence and prolonging survival. Targeting the vitamin D receptor (VDR) with analogs such as paricalcitol may improve chemotherapy effectiveness. This study evaluated the efficacy and safety of neoadjuvant albumin-bound paclitaxel (nab-paclitaxel) plus cisplatin plus gemcitabine (NABPLAGEM) plus paricalcitol (NCT03138720). METHODS: Participants were ≥18 years, had stage I-III PDAC without prior chemotherapy or radiation, Karnofsky Performance Status ≥70, and elevated CA 19-9. Study treatment included nab-paclitaxel (125 mg/m2), cisplatin (25 mg/m2), gemcitabine (1000 mg/m2), and paricalcitol (25 mcg) on days 1 and 8 of a 21-day cycle for up to 6 months. The primary outcome was CA 19-9 normalization. Secondary outcomes included margin-negative resection (R0), pathologic complete response (pCR), radiologic response, safety, and survival. Microbiome was analyzed as an exploratory outcome. RESULTS: Thirty-two participants were enrolled with median age 69.4 years, 56.2% male, and 93.8% white. Patients had resectable (cohort A, n = 10) and borderline resectable/locally advanced (cohort B, n = 22) tumors. CA 19-9 normalization occurred in 14 patients (43.8%). Two patients (6.2%) achieved pCR, and 19 (59.4%) achieved R0. Complete or partial radiologic response occurred in 39.3% of patients. Adverse events included grade 3-4 anemia (43.8%) and thrombocytopenia (59.4%). Median (95% CI) overall survival was 43.2 (7.5-upper bound not achieved) and 18.4 (10.9-41.2) months for cohorts A and B, respectively. CONCLUSION: Neoadjuvant NABPLAGEM plus paricalcitol demonstrated a high CA 19-9 normalization rate and was fairly well tolerated.