An Open Label Randomized Phase II Study of SOM230 and Everolimus in Castrate-Resistant, Chemotherapy-Naïve Prostate Cancer Patients
Prostate cancer cells typically have neuroendocrine (NE) differentiation features after they
become resistant to hormonal therapy. Somatostatin (SST - a peptide hormone) receptors
(SSTR) are usually expressed in a high level in these advanced prostate cancer cells. When
SSTR is activated pharmacologically by drugs similar to SST, prostate cancer cell growth is
inhibited. SOM230 is a new agent which can activate SSTR and block other key survival
molecules/pathways such as phosphatidylinositol 3-kinases (PI3K), mitogen-activated protein
(MAP) kinases (MAPK) signaling pathways. Thus SOM230 itself has anticancer activity for
It is also well known that hormonal refractory prostate cancer can grow in an environment of
very low male hormone level because of the activation of several non-androgen receptor
survival pathways. One key survival pathway is mediated by an important molecule called
mammalian target of rapamycin (mTOR). Drugs, such as Everolimus, have anticancer activity
in prostate cancer pre-clinically, but do not sustain its activity. The reason was that
cancer cells can up-regulate other survival pathways such as PI3K, MAPK, thus bypass mTOR.
It is hypothesized that SOM230 not only have anti-tumor effect in prostate cancer directly,
but also can block the up-regulated (feed-back loop), alternative PI3K or MAPK survival
pathways induced by mTOR inhibitors.
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.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Progression of Disease
Progression of disease is defined as disease progression by RECIST 1.1 criteria on CT scan (X-ray computed tomography), or appearance of > 2 new bone lesions on bone scan, or prostate-specific antigen (PSA) progression by Prostate Cancer Clinical Trials Working Group (PCWG2) criteria or death from any cause.
Proportion of patients alive and progression free after 12 weeks of treatment
Jianqing Lin, MD
Thomas Jefferson University
United States: Food and Drug Administration
|Yale Cancer Center||New Haven, Connecticut 06520-8028|
|Thomas Jefferson University||Philadelphia, Pennsylvania 19107-6541|