Assessment of Safety and Therapeutic Efficacy of Promitil in Combination With Folfox in Patients With GI Malignancies

Summary

This single center, Phase 1b, prospective, dose limiting toxicity (DLT)-clearing study, will assess the safety and efficacy of intravenously administered PROMITIL in combination with FOLFOX in cancer patients with inoperable, locally advanced or metastatic GI solid tumors. Based on previous clinical results, we hypothesized that the addition of PROMITIL to FOLFOX, a treatment protocol consisting of oxaliplatin and fluoropyrimidine and commonly used to treat gastrointestinal (GI) malignancies, may enhance the overall efficacy of this combination regimen while maintain a reasonable safety profile.

Timeline

Start

2021-01-13

Primary completion

2023-09-10

Completion

2023-09-12

Outcome

Outcome not reported

Stopped: “Investigational drug not available”

Publications

• Background Gabizon A, Shmeeda H, Tahover E, Kornev G, Patil Y, Amitay Y, Ohana P, Sapir E, Zalipsky S. Development of Promitil(R), a lipidic prodrug of mitomycin c in PEGylated liposomes: From bench to bedside. Adv Drug Deliv Rev. 2020;154-155:13-26. doi: 10.1016/j.addr.2020.07.027. Epub 2020 Aug 7.
• Background Amitay Y, Shmeeda H, Patil Y, Gorin J, Tzemach D, Mak L, Ohana P, Gabizon A. Pharmacologic Studies of a Prodrug of Mitomycin C in Pegylated Liposomes (Promitil((R))): High Stability in Plasma and Rapid Thiolytic Prodrug Activation in Tissues. Pharm Res. 2016 Mar;33(3):686-700. doi: 10.1007/s11095-015-1819-7. Epub 2015 Nov 16.
• Results Gabizon AA, Tahover E, Golan T, Geva R, Perets R, Amitay Y, Shmeeda H, Ohana P. Pharmacokinetics of mitomycin-c lipidic prodrug entrapped in liposomes and clinical correlations in metastatic colorectal cancer patients. Invest New Drugs. 2020 Oct;38(5):1411-1420. doi: 10.1007/s10637-020-00897-3. Epub 2020 Jan 18.
• Results Golan T, Grenader T, Ohana P, Amitay Y, Shmeeda H, La-Beck NM, Tahover E, Berger R, Gabizon AA. Pegylated liposomal mitomycin C prodrug enhances tolerance of mitomycin C: a phase 1 study in advanced solid tumor patients. Cancer Med. 2015 Oct;4(10):1472-83. doi: 10.1002/cam4.491. Epub 2015 Jul 14.

Drugs

Indications