Date: 2012-12-06
Type of information:
phase: 1b
Announcement: presentation of resultats at the San Antonio Breast Cancer Symposium and announcement of a new trial
Company: Dompé (Italy)
Product: reparixin
Action mechanism: Reparixin is a potent selective chemokine interleukin-8 inhibitor developed by Dompè Italian R&D laboratories. Reparixin is an inhibitor of the CXCR1 receptor which in the body is activated by chemokine interleukin-8 that plays a key role in anti-inflammatory response. It is the first in a novel class of low-molecular weight inhibitors that can selectively modulate the receptor activity via an allosteric mechanism of action. An allosteric inhibitor can freeze the receptor in an inactive position binding it to a different site than the site taken by the natural ligand (IL-8).
Disease: HER-2 negative metastatic breast cancer
Therapeutic area: Cancer - Oncology
Country: USA
Trial details: REP0210 is a pilot clinical study in 40 patients with operable breast cancer, subdivided in 2 different subgroups based on the receptor characteristics of the tumor, and treated in monotherapy with reparixin orally before surgical treatment. The study aims at evaluating, in the two subgroups, the effects of reparixin on cancer stem cells (CSCs) in early stage tumors and in the tumoral microenvironment, namely to verify whether Reparixin is effectively able to reduce CSCs and related markers, and to evaluate possible differences between the two subgroups with the aim to precisely identify the “ideal” target population for this innovative treatment. The two subgroups of patients will be Estrogen Receptor positive (ER+) and/or Progesterone Receptor positive (PR+)/HER2– respectively, and ER– and/or PR–/HER2–. CSCs will be measured through cytofluorimetry in samples of bioptic tissue, which will be subjected to PCR-RT and/or immunohistochemistry and to the dosage of: epithelial-mesenchymal markers, of the serine/threonine protein-kinase AKT, of the focal-adhesion-kinase(FAK) and of receptor CXR1 levels. Analogously, the study will also measure antinflammatory and angiogenesis marker levels, infiltrating leucocytes and markers of autophagy (P62 and LC3).
Latest
news: Dompé has presented a clinical trial at the 34th CTRC-AACR San Antonio Breast Cancer Symposium in Texas, US. This phase 1b clinical trial evaluating reparixin combined with chemotherapy for the treatment of metastatic breast cancer is currently enrolling to the third cohort. The study will involve 15 patients in 3 different centers in the US and is expected to complete by the first quarter 2013. The second cohort has been completed in patients where limiting toxicity has not been observed, supporting the safety profile for the candidate drug. The evaluation of the third cohort is being carried out and will be completed in the first quarter 2013. A further 9 patients are expected to be enrolled at 3 prominent Oncological Centers in the US. Based on the excellent safety profile demonstrated, it has been announced, at SABCS, the setting up of a new, important, clinical study aimed at evaluating the effects of Reparixin in oral monotherapy on CSCs and on tumor microenvironment for the treatment of women with early stage breast cancer, before surgery.
The study will involve a total of 7 Clinical Centers in the US coordinated by Dr Lori Goldstein, Director of the Breast Evaluation Center and leader of the Breast Cancer Research Program at of the Department of Medical Oncology at the Fox Chase Cancer Center of Philadelphia (US). The first center that has been activated is the Methodist Hospital Research Institute of Houston, Texas, which is expected to enroll the first patient in December. The primary objective of the study is the evaluation, in women over 18 with HER-2 metastatic breast cancer, of the pharmacokinetic and safety profile for the combined treatment with Reparixin on CSCs, on the tumoral microenvironment and on plasmatic levels of inflammatory cytokines, and the analysis of the tumor response to the treatment as an indicator of efficacy.
Patients receive a cycle of 3 days of treatment with Reparixin oral tablets 3 times a day followed by a cycle of combined treatment with paclitaxel 80mg/m2/week + oral Reparixin 3 times per day for 21 days, in three different dosages (400 mg, 800 mg, 1200 mg). Safety is evaluated after the first cycle, and the treatment will continue until the observation of clinical benefits. Currently, the second cohort of 3 patients where no toxicity has been observed has been completed to confirm the safety profile of the candidate drug. The third cohort is currently enrolling and will be concluded in the first trimester 2013. Another 10 patients are expected to be enrolled at three clinical sites in the US.
