Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer.

Abstract

BACKGROUND:

We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose.

METHODS:

Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using (99)Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry.

RESULTS:

Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1 ± 8.9 vs 31.3 ± 12.9 mg (P = 0.01). Both, AUC24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P < 0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P = 0.03) in tumour specimens.

CONCLUSION:

Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.

• Authors: M R Sarduy, I García, M A Coca, A Perera, L A Torres, C M Valenzuela, I Baladrón, M Solares, V Reyes, I Hernández, Y Perera, Y M Martínez, L Molina, Y M González, J A Ancízar, A Prats, L González, C A Casacó, B E Acevedo, P A López-Saura, D F Alonso, R Gómez, S E Perea-Rodríguez, CERVIFARM-300-II Study Group
• Journal: British journal of cancer (Br J Cancer) Vol. 112 Issue 10 Pg. 1636-43 (May 12 2015) ISSN: 1532-1827 [Electronic] England
• PMID: 25880012 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• NPM1 protein, human
• Nuclear Proteins
• Peptides, Cyclic
• Nucleophosmin
• CIGB-300

Topics

• Adult
• Area Under Curve
• Double-Blind Method
• Down-Regulation (drug effects)
• Female
• Half-Life
• Humans
• Injections, Intralesional (methods)
• Middle Aged
• Nuclear Proteins (metabolism)
• Nucleophosmin
• Peptides, Cyclic (administration & dosage)
• Uterine Cervical Neoplasms (drug therapy, metabolism)