Gong Jun, Osipov Arsen, Lorber Jeremy, Tighiouart Mourad, Kwan Albert K, Muranaka Hayato, Akinsola Rasaq, Billet Sandrine, Levi Abrahm, Abbas Anser, Davelaar John, Bhowmick Neil, Hendifar Andrew E
Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Biostatistics and Bioinformatics Research Center, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Biomedicines. 2023 May 8;11(5):1392. doi: 10.3390/biomedicines11051392.
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 ( = 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.
晚期胰腺癌的特点是治疗抵抗不断进展，5年生存率低至3%，令人沮丧。临床前数据表明，补充谷氨酰胺而非剥夺谷氨酰胺，单独或与吉西他滨联合使用时，对胰腺导管腺癌（PDAC）具有剂量依赖性的抗肿瘤作用。GlutaPanc I期试验是一项单臂、开放标签的临床试验，旨在研究L-谷氨酰胺、吉西他滨和纳米白蛋白结合型紫杉醇联合用药在16例未经治疗的局部晚期不可切除或转移性胰腺癌患者中的安全性。在为期7天的L-谷氨酰胺导入期之后，通过贝叶斯设计的剂量探索阶段开始，治疗周期为28天，直至疾病进展、出现不耐受或患者退出。主要目标是确定L-谷氨酰胺、吉西他滨和纳米白蛋白结合型紫杉醇联合用药的推荐II期剂量（RP2D）。次要目标包括所有剂量水平联合用药的安全性以及抗肿瘤活性的初步证据。探索性目标包括评估多个时间点血浆代谢物的变化以及补充L-谷氨酰胺前后粪便微生物群的变化。如果这项I期临床试验证明L-谷氨酰胺与纳米白蛋白结合型紫杉醇和吉西他滨联合使用的可行性，我们将推进该联合用药方案的研发，使其成为转移性胰腺癌患者一线全身治疗的选择，这是一个急需更多治疗方法的高危亚组。
