Phase 2 study of nintedanib for advanced progressing carcinoid tumors underway

By Liz Meszaros, MDLinx
Published October 23, 2017

Key Takeaways

Researchers have begun a phase 2 evaluation of nintedanib for the treatment of advanced progressing carcinoid tumors, according to reports given at the North American Neuroendocrine Tumor Society (NANETS) 2017 Symposium, October 19-21, 2017, in Philadelphia, PA.

“Serotonin is the cause of carcinoid symptoms and can signal the formation of fibroblasts via fibroblast growth receptors (FGFR). Nintedanib is an oral inhibitor of the FGFR pathway and several angiogenic signaling pathways thought to drive carcinoid tumor progression. We hypothesized that nintedanib may slow tumor progression in patients with progressing carcinoids,” noted Renuka Iyer, MD, professor of oncology; co-director, Liver and Pancreas Tumor Center; and section chief, Gastrointestinal Oncology, Roswell Park Cancer Institute, Buffalo, NY, and colleagues.

Nintedanib was developed by Boehringer Ingelheim, and is currently approved for the treatment of idiopathic pulmonary fibrosis and some types of non-small-cell lung cancer.

“We hypothesize that nintedanib may slow tumor progression in patients with progressing carcinoids,” reported Dr. Iyer and fellow researchers.

For this study, they plan to include 30 patients with unresectable/metastatic carcinoids treated with a stable dose of somatostatin analogue for 3 months or more. The primary endpoint is progression-free survival (PFS). In carcinoid tumors, a true PFS rate at 16 weeks of less than P=0.40 is considered unacceptable. If this occurs, the treatment will be deemed unworthy of further study.

Secondary endpoints included objective response rates, overall survival, change in quality of life, and toxicity.

As of June 2017, study accrual has been completed, and Dr. Iyer and fellow researchers are conducting their analyses. They will compile data for steady-state pharmacokinetics of nintedanib, Treg, and cytokine expression and growth factor data in groups based on response. In a subset analysis, they will assess gene mutations and copy number alterations on the mTOR pathway, as well as protein expression of AKT activation and other downstream targets.

“The 16-week PFS endpoint was just completed by all patients, six patients remain on study,” wrote these researchers. “No unexpected toxicity signal was seen.”

Study results are expected to be available in 2017-2018.

This study was funded by NCCN and Boehringer Ingelheim.

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