Combination L-Glutamine with Gemcitabine and Nab-Paclitaxel in Treatment-Naïve Advanced Pancreatic Cancer: The Phase I GlutaPanc Study Protocol

Abstract

Advanced pancreatic cancer is underscored by progressive therapeutic resistance and a dismal 5-year survival rate of 3%. Preclinical data demonstrated glutamine supplementation, not deprivation, elicited antitumor effects against pancreatic ductal adenocarcinoma (PDAC) alone and in combination with gemcitabine in a dose-dependent manner. The GlutaPanc phase I trial is a single-arm, open-label clinical trial investigating the safety of combination L-glutamine, gemcitabine, and nab-paclitaxel in subjects (n = 16) with untreated, locally advanced unresectable or metastatic pancreatic cancer. Following a 7-day lead-in phase with L-glutamine, the dose-finding phase via Bayesian design begins with treatment cycles lasting 28 days until disease progression, intolerance, or withdrawal. The primary objective is to establish the recommended phase II dose (RP2D) of combination L-glutamine, gemcitabine, and nab-paclitaxel. Secondary objectives include safety of the combination across all dose levels and preliminary evidence of antitumor activity. Exploratory objectives include evaluating changes in plasma metabolites across multiple time points and changes in the stool microbiome pre and post L-glutamine supplementation. If this phase I clinical trial demonstrates the feasibility of L-glutamine in combination with nab-paclitaxel and gemcitabine, we would advance the development of this combination as a first-line systemic option in subjects with metastatic pancreatic cancer, a high-risk subgroup desperately in need of additional therapies.

Keywords: L-glutamine; chemotherapy; clinical trial; gemcitabine; metastatic; nab-paclitaxel; pancreatic cancer.

Figure 1

Study Schema of the GlutaPanc trial. A single-institution, open-label, single-arm, non-randomized, phase I clinical trial investigating the feasibility of combination L-glutamine, gemcitabine, and nab-paclitaxel in treatment-naïve, unresectable or metastatic pancreatic cancer. The primary objective is to determine the recommended phase II dose (RP2D) of combination L-glutamine, gemcitabine, and nab-paclitaxel in this patient population. PDAC, pancreatic ductal adenocarcinoma; ECOG PS, Eastern Cooperative Oncology Group (ECOG) performance status; BID, twice daily; ORR, overall response rate; PFS, progression-free survival; OS, overall survival.