Pasireotide (SOM230) With or Without Everolimus in Treating Patients With Hormone Resistant, Chemotherapy Naive Prostate Cancer
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Purpose
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).
| Condition | Intervention | Phase |
|---|---|---|
|
Castrate Resistant Prostate Cancer Chemotherapy Naive Prostate Cancer Prostate Cancer |
Drug: Pasireotide Drug: Everolimus Other: Laboratory biomarker analysis |
Phase 2 |
| Study Type: | Interventional |
| 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
| Estimated Enrollment: | 64 |
| Study Start Date: | June 2011 |
| Estimated Study Completion Date: | June 2016 |
| Estimated Primary Completion Date: | June 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Cohort A (pasireotide)
Patients receive pasireotide IM once every 4 weeks
|
Drug: Pasireotide
Given IM
Other Name: SOM230
Other: Laboratory biomarker analysis
Correlative studies
|
|
Experimental: Cohort B (pasireotide and everolimus)
Patients receive pasireotide as in cohort A and everolimus PO QD
|
Drug: Pasireotide
Given IM
Other Name: SOM230
Drug: Everolimus
Given PO
Other Names:
Other: Laboratory biomarker analysis
Correlative studies
|
Detailed Description:
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Male |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age minimum: 18 years old
- Histological confirmation of prostatic adenocarcinoma
- PSA > or = to 2 ng/ml
- PSA progression (serially rises on two occasions each at least one week apart) OR disease progression on imaging studies (CT scan or bone scan).
- Minimally symptomatic - no symptoms attributed to prostate cancer greater than Grade I based on NCI CTCAE Version 4.0 grading of toxicities
- Discontinuation of all antiandrogen, ketoconazole and investigational drugs for at least 4 weeks (6 weeks for bicalutamide) prior to study initiation
- Maintain castrate levels of testosterone (<50ng/dL)
- Karnofsky Performance Status > or = to 60%
- Life expectancy > 3 months
- Adequate hematologic, renal, and liver function
Exclusion Criteria:
- Currently active second malignancy other than non-melanoma skin cancers.
- Clinically significant cardiovascular disease: EF < 30%, NHYA Class III or greater congestive heart failure, myocardial infarction/unstable angina within 6 months prior to study enrollment, or significant ECG abnormalities such as QRS/QT prolongation (see Section 5.3).
- Progressive pulmonary disease, such as advanced COPD, pulmonary fibrosis, or supplemental O2 requirement.
- Known CNS disease, except for treated brain metastases.
- Poorly controlled diabetes mellitus (HbA1c > 7 %) or fasting blood glucose level >126 mg/dL in non-diabetic patients or > 189 mg/dL in diabetic patients (can be enrolled after initiation or titration of anti-diabetic agent(s)).
- Poorly controlled hypercholesterolemia (fasting serum cholesterol >300 mg/dL) or hypertriglyceridemia (> 2.5 x ULN). Patients above either threshold can be included after initiation of appropriate lipid lowering medication.
- Current use of chronic steroids (equivalent of 20mg prednisone daily). Inhaled steroids are acceptable.
- Active gallbladder disease or hepatitis (AST or ALT > 2.0, or bilirubin > 1.5x ULN), liver cirrhosis, or severe liver impairment (Child-Pugh class C). It is highly recommended that patients positive for HBV-DNA or HBsAg are treated prophylactically with an antiviral for 1-2 weeks prior to receiving study drug.
- Serum creatinine >1.5 upper limit of normal or on dialysis.
- Prior use of a somatostatin analog or mTOR inhibitor for the treatment of PC.
Contacts and Locations| Contact: Jianqing Lin, MD | 215-955-8874 | |
| Contact: Clinical Research Management Office | 215-955-1661 |
| United States, Connecticut | |
| Yale Cancer Center | Not yet recruiting |
| New Haven, Connecticut, United States, 06520 | |
| Contact: Hari Deshpande, MD 203-737-5312 | |
| Principal Investigator: Hari Deshpande, MD | |
| Sub-Investigator: Geoffrey Gibney, MD | |
| Sub-Investigator: Adrienne Joy Burns, PA | |
| Sub-Investigator: Michael Hurwitz, MD | |
| United States, Pennsylvania | |
| Thomas Jefferson University | Recruiting |
| Philadelphia, Pennsylvania, United States, 19107 | |
| Contact: Jianqing Lin, MD 215-955-8874 | |
| Contact: Clinical Research Management Office 215-955-1661 | |
| Principal Investigator: Jianqing Lin, MD | |
| Sub-Investigator: William Kevin Kelly, DO | |
| Sub-Investigator: Jean Hoffman-Censits, MD | |
| Principal Investigator: | Jianqing Lin, MD | Thomas Jefferson University |
More Information
Additional Information:
No publications provided
| Responsible Party: | Thomas Jefferson University |
| ClinicalTrials.gov Identifier: | NCT01313559 History of Changes |
| Other Study ID Numbers: | 11D.78, 2010-52 |
| Study First Received: | March 10, 2011 |
| Last Updated: | December 5, 2012 |
| Health Authority: | United States: Food and Drug Administration United States: Institutional Review Board |
Keywords provided by Thomas Jefferson University:
|
Castrate Resistant Chemotherapy Naive Prostate Cancer SOM230 Everolimus |
Additional relevant MeSH terms:
|
Prostatic Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Neoplasms Everolimus Sirolimus Genital Diseases, Male Prostatic Diseases Immunosuppressive Agents |
Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antibiotics, Antineoplastic Antineoplastic Agents Therapeutic Uses Antifungal Agents Anti-Infective Agents Anti-Bacterial Agents |
ClinicalTrials.gov processed this record on May 19, 2013