Back to results

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

Primary Purpose

Castrate Resistant Prostate Cancer, Chemotherapy Naive Prostate Cancer, Prostate Cancer

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Pasireotide

Everolimus

Laboratory biomarker analysis

About this trial

This is an interventional treatment trial for Castrate Resistant Prostate Cancer focused on measuring Castrate Resistant, Chemotherapy Naive, Prostate Cancer, SOM230, Everolimus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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.

Sites / Locations

Yale Cancer Center
Sidney Kimmel Cancer Center at Thomas Jefferson University

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Cohort A (pasireotide)

Cohort B (pasireotide and everolimus)

Arm Description

Patients receive pasireotide IM once every 4 weeks

Patients receive pasireotide as in cohort A and everolimus PO QD

Outcomes

Primary Outcome Measures

Number of Participants Alive and Progression Free After 12 Weeks of 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

Number of Participants With > 50% Decline From Baseline PSA Level

Number of Participants Without New Bone Lesions After 12 Weeks of Treatment

Number of Participants With Progression Free Survival (PFS) Based on RECIST 1.1 Criteria

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

Full Information

NCT ID

NCT01313559

First Posted

March 10, 2011

Last Updated

April 23, 2018

Sponsor

Sidney Kimmel Cancer Center at Thomas Jefferson University

Collaborators

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01313559

Brief Title

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

Official Title

An Open Label Randomized Phase II Study of SOM230 and Everolimus in Castrate-Resistant, Chemotherapy-Naïve Prostate Cancer Patients

Study Type

Interventional

2. Study Status

Record Verification Date

April 2018

Overall Recruitment Status

Terminated

Why Stopped

Slow accrual

Study Start Date

June 2011 (undefined)

Primary Completion Date

September 15, 2012 (Actual)

Study Completion Date

November 29, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sidney Kimmel Cancer Center at Thomas Jefferson University

Collaborators

Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Castrate Resistant Prostate Cancer, Chemotherapy Naive Prostate Cancer, Prostate Cancer

Keywords

Castrate Resistant, Chemotherapy Naive, Prostate Cancer, SOM230, Everolimus

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort A (pasireotide)

Arm Type

Active Comparator

Arm Description

Patients receive pasireotide IM once every 4 weeks

Arm Title

Cohort B (pasireotide and everolimus)

Arm Type

Experimental

Arm Description

Patients receive pasireotide as in cohort A and everolimus PO QD

Intervention Type

Drug

Intervention Name(s)

Pasireotide

Other Intervention Name(s)

SOM230

Intervention Description

Given IM

Intervention Type

Drug

Intervention Name(s)

Everolimus

Other Intervention Name(s)

42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001

Intervention Description

Given PO

Intervention Type

Other

Intervention Name(s)

Laboratory biomarker analysis

Intervention Description

Correlative studies

Primary Outcome Measure Information:

Title

Number of Participants Alive and Progression Free After 12 Weeks of Treatment

Description

Time Frame

12 weeks after treatment

Secondary Outcome Measure Information:

Title

Number of Participants With > 50% Decline From Baseline PSA Level

Time Frame

After 12 weeks of treatment

Title

Number of Participants Without New Bone Lesions After 12 Weeks of Treatment

Time Frame

After 12 weeks of treatment

Title

Number of Participants With Progression Free Survival (PFS) Based on RECIST 1.1 Criteria

Description

Time Frame

Assessed up to 30 days after completion of study treatment

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jianqing Lin, MD

Organizational Affiliation

Sidney Kimmel Cancer Center at Thomas Jefferson University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Yale Cancer Center

City

New Haven

State/Province

Connecticut

ZIP/Postal Code

06520

Country

United States

Facility Name

Sidney Kimmel Cancer Center at Thomas Jefferson University

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19107

Country

United States

12. IPD Sharing Statement

Links:

URL

http://hospitals.jefferson.edu/

Description

Thomas Jefferson University Hospital

Learn more about this trial

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

We'll reach out to this number within 24 hrs