Combination L-Glutamine with Gemcitabine and Nab-Paclitaxel in Treatment-Naïve Advanced Pancreatic Cancer: The Phase I GlutaPanc Study Protocol
Jun Gong,
Arsen Osipov,
Jeremy Lorber,
Mourad Tighiouart,
Albert K. Kwan,
Hayato Muranaka,
Rasaq Akinsola,
Sandrine Billet,
Abrahm Levi,
Anser Abbas,
John Davelaar,
Neil Bhowmick,
Andrew E. Hendifar
Affiliations
Jun Gong
Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Arsen Osipov
Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Jeremy Lorber
Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Mourad Tighiouart
Biostatistics and Bioinformatics Research Center, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Albert K. Kwan
Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Hayato Muranaka
Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Rasaq Akinsola
Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Sandrine Billet
Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Abrahm Levi
Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Anser Abbas
Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
John Davelaar
Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Neil Bhowmick
Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Andrew E. Hendifar
Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
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.
