Pasireotide (SOM230) With or Without Everolimus in Treating Patients With Hormone Resistant, Chemotherapy Naive Prostate Cancer
This is an open label randomized phase II study for prostate cancer patients who have disease progression after hormonal therapy. SOM230 LAR (Pasireotide) binds to its receptor of prostate cancer cells and can prevent them from growing. Everolimus works by targeting a cell survival factor in prostate cancer. The combination of these drugs may work better for the treatment of prostate cancer without toxic chemotherapy. Patients will receive either SOM230 LAR (group A) or SOM230 LAR in combination with Everolimus (group B).
Castrate Resistant Prostate Cancer
Chemotherapy Naive Prostate Cancer
Other: Laboratory biomarker analysis
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open Label Randomized Phase II Study of SOM230 and Everolimus in Castrate-Resistant, Chemotherapy-Naïve Prostate Cancer Patients|
- Progression of Disease [ Time Frame: Proportion of patients alive and progression free after 12 weeks of treatment ] [ Designated as safety issue: Yes ]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.
- PSA response rate based on > 50% decline from baseline PSA level [ Time Frame: After 12 weeks of treatment ] [ Designated as safety issue: No ]Will be reported as medians with standard error
- Radiographic response rate (partial response or complete response by RECIST 1.1 criteria and no new bone metastases on bone scan) [ Time Frame: After 12 weeks of treatment ] [ Designated as safety issue: No ]Reported as medians with standard error
- Median progression free survival (PFS) based on RECIST 1.1 criteria [ Time Frame: Assessed up to 30 days after completion of study treatment ] [ Designated as safety issue: No ]Reported as medians with standard error. Possible risk factors will be compared for survival with Kaplan-Meier estimates and log-rank tests.
- Observed toxicities and dose modifications of SOM230 alone and in combination with everolimus assessed using the NCICTCAE version 4.0 grading of toxicities [ Time Frame: Assessed up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]Summarized using exact methods
|Study Start Date:||June 2011|
|Estimated Study Completion Date:||June 2018|
|Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
Active Comparator: Cohort A (pasireotide)
Patients receive pasireotide IM once every 4 weeks
Other Name: SOM230Other: Laboratory biomarker analysis
Experimental: Cohort B (pasireotide and everolimus)
Patients receive pasireotide as in cohort A and everolimus PO QD
Other Name: SOM230Drug: Everolimus
Other Names:Other: Laboratory biomarker analysis
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 prostate cancer.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01313559
|United States, Connecticut|
|Yale Cancer Center|
|New Haven, Connecticut, United States, 06520|
|United States, Pennsylvania|
|Thomas Jefferson University|
|Philadelphia, Pennsylvania, United States, 19107|
|Principal Investigator:||Jianqing Lin, MD||Thomas Jefferson University|