Pasireotide (SOM230) With or Without Everolimus in Treating Patients With Hormone Resistant, Chemotherapy Naive Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01313559
Recruitment Status : Terminated (Slow accrual)
First Posted : March 11, 2011
Results First Posted : January 16, 2018
Last Update Posted : April 25, 2018
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )

Brief Summary:
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 or disease Intervention/treatment Phase
Castrate Resistant Prostate Cancer Chemotherapy Naive Prostate Cancer Prostate Cancer Drug: Pasireotide Drug: Everolimus Other: Laboratory biomarker analysis Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : June 2011
Actual Primary Completion Date : September 15, 2012
Actual Study Completion Date : November 29, 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
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:
  • 42-O-(2-hydroxy)ethyl rapamycin
  • Afinitor
  • RAD001

Other: Laboratory biomarker analysis
Correlative studies

Primary Outcome Measures :
  1. Number of Participants Alive and Progression Free After 12 Weeks of Treatment [ Time Frame: 12 weeks after treatment ]
    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.

Secondary Outcome Measures :
  1. Number of Participants With > 50% Decline From Baseline PSA Level [ Time Frame: After 12 weeks of treatment ]
  2. Number of Participants Without New Bone Lesions After 12 Weeks of Treatment [ Time Frame: After 12 weeks of treatment ]
  3. Number of Participants With Progression Free Survival (PFS) Based on RECIST 1.1 Criteria [ Time Frame: Assessed up to 30 days after completion of study treatment ]
    Progression free survival (PFS) based on primary outcome criteria for disease progression. Patients without radiographic disease progression who permanently discontinue the study drugs will be censored

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01313559

United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06520
United States, Pennsylvania
Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
Sponsors and Collaborators
Sidney Kimmel Cancer Center at Thomas Jefferson University
Novartis Pharmaceuticals
Principal Investigator: Jianqing Lin, MD Sidney Kimmel Cancer Center at Thomas Jefferson University

Additional Information:
Responsible Party: Sidney Kimmel Cancer Center at Thomas Jefferson University Identifier: NCT01313559     History of Changes
Other Study ID Numbers: 11D.78
2010-52 ( Other Identifier: CCRRC )
First Posted: March 11, 2011    Key Record Dates
Results First Posted: January 16, 2018
Last Update Posted: April 25, 2018
Last Verified: April 2018

Keywords provided by Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University ):
Castrate Resistant
Chemotherapy Naive
Prostate Cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists