Lipomedix launches an open-label, Phase 1b study of intravenously administered pegylated liposomal mitomycin C lipidated prodrug (PROMITIL) in combination with external beam radiotherapy in patients with advanced cancer requiring palliative radiotherapy for inoperable primary tumors or metastatic disease
The Phase 1b clinical study (LIPORAD-2018) was approved by the Israel Ministry of Health and is conducted in two Medical Centers in Israel. Patient recruitment started on January 2019.
This study launch follows encouraging preclinical and clinical data suggesting synergistic activity of the combination of Promitil® with radiotherapy (Tian X et al., Int. J. Radiation Oncol. Biol. Phys., 96:547-555, 2016; Tahover E et al., Front. Oncol., 8:544, 2018).
This will be an open-label, single-arm, prospective study, in which up to 18 patients requiring radiotherapy for metastatic disease or for an inoperable primary tumor with no definitive curative treatment option, will undergo a combination treatment comprised of intravenously delivered PROMITIL and standard of care radiotherapy
For further details on this Phase 1b clinical study and participating centers, refer to:
A Phase I, Dose-Escalating, Safety Study of an Intravenously Administered Pegylated-Liposomal Mitomycin-C Lipid-based Prodrug (PL-MLP, Promitil®) in Cancer Patients with Solid Tumors (completed and published, 2015)
A Phase 1A clinical study with Promitil® in patients with advanced-stage solid tumors was completed in Nov 2014. The study took place at two medical centers in Israel under the approval of the Israeli Ministry of Health. A total of 27 patients received 102 Promitil® infusions. Dose-limiting toxicity was thrombocytopenia. The maximal tolerated dose of Promitil® was found to be ~3-fold greater than for MMC in mg-equivalents, confirming that toxicity is substantially reduced. Pharmacokinetic analysis indicates that Promitil® has a slow blood clearance, with a half-life of ~1 day which is characteristic of pegylated liposomes. Anti-tumor activity was observed in various cancer types (Golan et al., Cancer Medicine 4:1472–1483, 2015).
This clinical study of Promitil was expanded to a Phase 1B in patients with advanced colorectal cancer, receiving a 3rd or later line of therapy. The objectives of this expanded phase of the study were to evaluate the safety and disease control rate of Promitil® given either as a single agent, or in combination with Capecitabine, and/or Bevacizumab. Capecitabine, an oral fluopyrimidine, and Bevacizumab, an anti-VEGF monoclonal antibody, are part of the standard therapy of colon cancer. The expanded phase was conducted in 4 medical sites in Israel (Shaare Zedek, Sheba, Ichilov, and Rambam) and completed accrual in mid-2017 of 61 patients in four cohorts, the final report was released in June 2018.
Promitil dosing in 61 mCRC patients, as a single agent or in combination with capecitabine and/or bevacizumab, demonstrated its relative high safety profile with encouraging signs of antitumor activity. Thus, Promitil is an effective tool to safely achieve a high dose intensity with a prodrug of mitomycin c. These preliminary findings will require validation in randomized phase 2-3 studies.