Safety Study of CALAA-01 to Treat Solid Tumor Cancers

Summary

Rationale: CALAA-01 is a targeted therapeutic designed to inhibit tumor growth and/or reduce tumor size. The active ingredient in CALAA-01 is a small interfering RNA (siRNA). This siRNA inhibits tumor growth via RNA interference to reduce expression of the M2 subunit of ribonucleotide reductase (R2). The CALAA-01 siRNA is protected from nuclease degradation within a stabilized nanoparticle targeted to tumor cells. PURPOSE: This phase I trial will: * Determine the safety, toxicity, and the maximum tolerated dose (MTD) of CALAA-01 when administered intravenously to patients with relapsed or refractory cancer. * Characterize the pharmacokinetics (PK) of CALAA-01 after intravenous administration. * Provide preliminary evidence of efficacy of intravenous CALAA-01 by evaluating tumor response. * Recommend a dose of intravenous CALAA-01 for future clinical studies. * Evaluate immune response, by measuring antibody and cytokine levels, and the effect of intravenous CALAA-01 on complement.

Timeline

Start

2008-05

Primary completion

2012-09

Completion

2012-09

Publications

• Background Heidel JD, Yu Z, Liu JY, Rele SM, Liang Y, Zeidan RK, Kornbrust DJ, Davis ME. Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunit M2 siRNA. Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5715-21. doi: 10.1073/pnas.0701458104. Epub 2007 Mar 22.
• Background Heidel JD, Liu JY, Yen Y, Zhou B, Heale BS, Rossi JJ, Bartlett DW, Davis ME. Potent siRNA inhibitors of ribonucleotide reductase subunit RRM2 reduce cell proliferation in vitro and in vivo. Clin Cancer Res. 2007 Apr 1;13(7):2207-15. doi: 10.1158/1078-0432.CCR-06-2218.
• Background Bartlett DW, Davis ME. Impact of tumor-specific targeting and dosing schedule on tumor growth inhibition after intravenous administration of siRNA-containing nanoparticles. Biotechnol Bioeng. 2008 Mar 1;99(4):975-85. doi: 10.1002/bit.21668.
• Background Heidel JD. Linear cyclodextrin-containing polymers and their use as delivery agents. Expert Opin Drug Deliv. 2006 Sep;3(5):641-6. doi: 10.1517/17425247.3.5.641.
• Results Davis ME, Zuckerman JE, Choi CH, Seligson D, Tolcher A, Alabi CA, Yen Y, Heidel JD, Ribas A. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature. 2010 Apr 15;464(7291):1067-70. doi: 10.1038/nature08956. Epub 2010 Mar 21.

Drugs

Indications