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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Thomas Jefferson University
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT01313559
First received: March 10, 2011
Last updated: September 5, 2014
Last verified: September 2014
  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

Resource links provided by NLM:


Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 2015 (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:
  • 42-O-(2-hydroxy)ethyl rapamycin
  • Afinitor
  • RAD001
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
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01313559

Contacts
Contact: Jianqing Lin, MD 215-955-8874
Contact: Clinical Research Management Office 215-955-1661

Locations
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         
Sponsors and Collaborators
Thomas Jefferson University
Novartis Pharmaceuticals
Investigators
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: September 5, 2014
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
Neoplasms
Neoplasms by Site
Urogenital Neoplasms
Everolimus
Sirolimus
Genital Diseases, Male
Prostatic Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014