Neratinib and Everolimus, Palbociclib, or Trametinib in Treating Participants With Refractory and Advanced or Metastatic Solid Tumors With EGFR Mutation/Amplification, HER2 Mutation/Amplification, or HER3/4 Mutation or KRAS Mutation

Summary

This phase I trial studies the side effects and best dose of neratinib in combination with everolimus, palbociclib, or trametinib in participants with solid tumors with EGFR mutation/amplification, HER2 mutation/amplification, HER3/4 mutation, or KRAS mutation that do not respond to treatment (refractory) and have spread to other parts of the body (advanced or metastatic). Neratinib, palbociclib, and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as everolimus, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving neratinib with everolimus, palbociclib, or trametinib may work better than neratinib alone in treating participants with solid tumors.

Timeline

Start

2017-10-31

Primary completion

2028-10-01

Completion

2028-10-01

Publications

• Piha-Paul SA, Tseng C, Tran HT, Gao M, Karp DD, Subbiah V, Tsimberidou AM, Kawedia JD, Fu S, Pant S, Yap TA, Morris VK, Kee BK, Blum Murphy M, Lim J, Meric-Bernstam F. A phase I trial of the pan-ERBB inhibitor neratinib combined with the MEK inhibitor trametinib in patients with advanced cancer with EGFR mutation/amplification, HER2 mutation/amplification, HER3/4 mutation or KRAS mutation. Cancer Chemother Pharmacol. 2023 Aug;92(2):107-118. doi: 10.1007/s00280-023-04545-4. Epub 2023 Jun 14.

Drugs

Indications