New Prostate Cancer Clinical Trial

An open label randomized phase II study of SOM230 LAR and Everolimus in castrate resistant, chemotherapy-naïve prostate cancer patients

This trial concept was developed by Dr. Kevin Kelly one year ago. The goal of this study is to develop a new well tolerated therapy that can be offered to prostate cancer patients prior to receiving chemotherapy.

It is well known that mTOR is a therapeutic target for castrate resistant prostate cancer (CRPC). But mTOR inhibitors do not have sustained activity for CRPC. Inactivation of S6Kinase by mTOR inhibitors results in a feedback hyperactive growth factor-receptor tyrosine kinase-PI3K-Akt and Ras-Raf1-MEK1/2-ERK pathways which may contribute to cancer cell’s resistance to mTOR inhibition.

Prostate cancer cells usually have neuroendocrine (NE) differentiation features after they become castrate resistant. Somatostatin (SST) receptors (SSTR) are expressed in a high level in these advanced prostate cancer cells. When SSTR is activated pharmacologically by drugs similar to SST, the prostate cancer cell growth is inhibited.

Preclinical data supported that SSTR agonist SOM230 not only has anti-tumor effect directly, but also can block the up-regulated (feed-back loop), alternative PI3K or MAPK survival pathways induced by mTOR inhibitors. This phase II study is designed to see if SOM230 and Everolimus combination can achieve disease control without chemotherapy.

Patients will be randomized in a 1:1 fashion to either SOM230 alone (Cohort A) or SOM230 plus Everolimus in combination (Cohort B). A Simon optimal two stage design will be utilized and a “pick the winner” approach will determine which regimen will be recommended for further evaluation. The primary endpoint is to determine the proportion of patients with progression free of disease at 12 weeks. Serum cytokine/cell-signalling panel (includes Interleukins,VEGF, IGF-1 etc) and neuroendocrine differentiation biomarkers will be examined. Akt/mTOR pathway target assessment will be performed in skin biopsy specimen.

The trial is ready to be opened for accrual and Jefferson will lead the trial. Yale Cancer Center will also participate this study.

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