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

• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01313559
• Collaborator: Novartis Pharmaceuticals (Industry)
• Enrollment: 6
• Locations: 2
• Arms: 2
• Duration (Months): 18
• Patients Per Site: 3
• Patients Per Site Per Month: 0.2

Study Details

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).

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 Design

• Study Type: Interventional
• 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: Jun 1, 2011
• Actual Primary Completion Date: Sep 15, 2012
• Actual Study Completion Date: Nov 29, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Cohort A (pasireotide) Patients receive pasireotide IM once every 4 weeks	Drug: Pasireotide; Given IM; Other Names: 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 Names: SOM230 ; Drug: Everolimus; Given PO; Other Names: 42-O-(2-hydroxy)ethyl rapamycin Afinitor RAD001 ; Other: Laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Number of Participants Alive and Progression Free After 12 Weeks of Treatment [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 [After 12 weeks of treatment]

2. Number of Participants Without New Bone Lesions After 12 Weeks of Treatment [After 12 weeks of treatment]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Yale Cancer Center	New Haven	Connecticut	United States	06520
2	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

Investigators

• Principal Investigator: Jianqing Lin, MD, Sidney Kimmel Cancer Center at Thomas Jefferson University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center
• Thomas Jefferson University Hospital

Publications

None provided.

• Responsible Party: Sidney Kimmel Cancer Center at Thomas Jefferson University
• ClinicalTrials.gov Identifier: NCT01313559
• Other Study ID Numbers: 11D.78; 2010-52
• First Posted: Mar 11, 2011
• Last Update Posted: Apr 25, 2018
• Last Verified: Apr 1, 2018

• Keywords provided by Sidney Kimmel Cancer Center at Thomas Jefferson University: Castrate Resistant; Chemotherapy Naive; Prostate Cancer; SOM230; Everolimus
• Additional relevant MeSH terms: Prostatic Neoplasms; Everolimus; Pasireotide

Study Results

Participant Flow

Arm/Group Title	Cohort A (Pasireotide)	Cohort B (Pasireotide and Everolimus)
Arm/Group Description	Patients receive pasireotide IM once every 4 weeks Pasireotide: Given IM Laboratory biomarker analysis: Correlative studies	Patients receive pasireotide as in cohort A and everolimus PO QD Pasireotide: Given IM Everolimus: Given PO Laboratory biomarker analysis: Correlative studies
Period Title: Overall Study
STARTED	4	2
COMPLETED	0	0
NOT COMPLETED	4	2

Baseline Characteristics

Arm/Group Title	Cohort A (Pasireotide)	Cohort B (Pasireotide and Everolimus)	Total
Arm/Group Description	Patients receive pasireotide IM once every 4 weeks Pasireotide: Given IM Laboratory biomarker analysis: Correlative studies	Patients receive pasireotide as in cohort A and everolimus PO QD Pasireotide: Given IM Everolimus: Given PO Laboratory biomarker analysis: Correlative studies	Total of all reporting groups
Overall Participants	4	2	6
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	0 0%	1 50%	1 16.7%
>=65 years	4 100%	1 50%	5 83.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	78.0 (4.6)	69.4 (8.4)	75.2 (6.8)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	4 100%	2 100%	6 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	4 100%	2 100%	6 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 25%	0 0%	1 16.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 25%	0 0%	1 16.7%
White	2 50%	2 100%	4 66.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	4 100%	2 100%	6 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Alive and Progression Free After 12 Weeks of Treatment
Description	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.
Time Frame	12 weeks after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort A (Pasireotide)	Cohort B (Pasireotide and Everolimus)
Arm/Group Description	Patients receive pasireotide IM once every 4 weeks Pasireotide: Given IM Laboratory biomarker analysis: Correlative studies	Patients receive pasireotide as in cohort A and everolimus PO QD Pasireotide: Given IM Everolimus: Given PO Laboratory biomarker analysis: Correlative studies
Measure Participants	4	2
Number [participants]	0 0%	0 0%

2. Secondary Outcome

Title	Number of Participants With > 50% Decline From Baseline PSA Level
Time Frame	After 12 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort A (Pasireotide)	Cohort B (Pasireotide and Everolimus)
Arm/Group Description	Patients receive pasireotide IM once every 4 weeks Pasireotide: Given IM Laboratory biomarker analysis: Correlative studies	Patients receive pasireotide as in cohort A and everolimus PO QD Pasireotide: Given IM Everolimus: Given PO Laboratory biomarker analysis: Correlative studies
Measure Participants	4	2
Number [participants]	2 50%	0 0%

3. Secondary Outcome

Title	Number of Participants Without New Bone Lesions After 12 Weeks of Treatment
Time Frame	After 12 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort A (Pasireotide)	Cohort B (Pasireotide and Everolimus)
Arm/Group Description	Patients receive pasireotide IM once every 4 weeks Pasireotide: Given IM Laboratory biomarker analysis: Correlative studies	Patients receive pasireotide as in cohort A and everolimus PO QD Pasireotide: Given IM Everolimus: Given PO Laboratory biomarker analysis: Correlative studies
Measure Participants	4	2
Number [participants]	0 0%	0 0%

4. Secondary Outcome

Title	Number of Participants With Progression Free Survival (PFS) Based on RECIST 1.1 Criteria
Description	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
Time Frame	Assessed up to 30 days after completion of study treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cohort A (Pasireotide)	Cohort B (Pasireotide and Everolimus)
Arm/Group Description	Patients receive pasireotide IM once every 4 weeks Pasireotide: Given IM Laboratory biomarker analysis: Correlative studies	Patients receive pasireotide as in cohort A and everolimus PO QD Pasireotide: Given IM Everolimus: Given PO Laboratory biomarker analysis: Correlative studies
Measure Participants	4	2
Number [participants]	0 0%	0 0%

Adverse Events

Arm/Group Title	Cohort A (Pasireotide)		Cohort B (Pasireotide and Everolimus)
Arm/Group Description	Patients receive pasireotide IM once every 4 weeks Pasireotide: Given IM Laboratory biomarker analysis: Correlative studies		Patients receive pasireotide as in cohort A and everolimus PO QD Pasireotide: Given IM Everolimus: Given PO Laboratory biomarker analysis: Correlative studies
All Cause Mortality
	Cohort A (Pasireotide)		Cohort B (Pasireotide and Everolimus)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cohort A (Pasireotide)		Cohort B (Pasireotide and Everolimus)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/4 (25%)		0/2 (0%)
Blood and lymphatic system disorders
Elevated creatinine	1/4 (25%)	1	0/2 (0%)	0
Renal and urinary disorders
Urinary tract obstruction	1/4 (25%)	1	0/2 (0%)	0
Other (Not Including Serious) Adverse Events
	Cohort A (Pasireotide)		Cohort B (Pasireotide and Everolimus)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		2/2 (100%)
Blood and lymphatic system disorders
Anemia	1/4 (25%)	1	0/2 (0%)	0
Elevated creatinine	0/4 (0%)	0	1/2 (50%)	2
Elevated transaminase	0/4 (0%)	0	1/2 (50%)	1
Hyperglycemia	3/4 (75%)	5	2/2 (100%)	6
Hypertension	1/4 (25%)	1	0/2 (0%)	0
Hypocalcemia	1/4 (25%)	1	0/2 (0%)	0
Hypokalemia	1/4 (25%)	1	0/2 (0%)	0
Hypophosphatemia	1/4 (25%)	1	0/2 (0%)	0
Cardiac disorders
Sinus bradycardia	1/4 (25%)	1	0/2 (0%)	0
Gastrointestinal disorders
Constipation	1/4 (25%)	1	1/2 (50%)	1
Diarrhea	2/4 (50%)	2	1/2 (50%)	2
Dyspepsia	1/4 (25%)	1	0/2 (0%)	0
Gastroesophageal reflux disease	1/4 (25%)	1	0/2 (0%)	0
General disorders
Abdominal pain	1/4 (25%)	1	0/2 (0%)	0
Anorexia	2/4 (50%)	2	1/2 (50%)	1
Chest discomfort	1/4 (25%)	1	0/2 (0%)	0
Chills	0/4 (0%)	0	1/2 (50%)	2
Cough	1/4 (25%)	1	1/2 (50%)	1
Decreased appetite	0/4 (0%)	0	1/2 (50%)	1
Dehydration	2/4 (50%)	3	1/2 (50%)	1
Dizziness	2/4 (50%)	3	0/2 (0%)	0
Dry mouth	1/4 (25%)	1	1/2 (50%)	1
Dry skin	0/4 (0%)	0	1/2 (50%)	1
Dysgeusia	0/4 (0%)	0	1/2 (50%)	1
Fall	1/4 (25%)	1	0/2 (0%)	0
Fatigue	3/4 (75%)	3	2/2 (100%)	4
Flatulence	2/4 (50%)	2	0/2 (0%)	0
Headache	3/4 (75%)	4	0/2 (0%)	0
Hip pain	0/4 (0%)	0	1/2 (50%)	1
Hot flashes	1/4 (25%)	1	0/2 (0%)	0
Mood alteration	1/4 (25%)	1	0/2 (0%)	0
Mucositis	0/4 (0%)	0	2/2 (100%)	2
Muscular pain	1/4 (25%)	1	0/2 (0%)	0
Nausea	1/4 (25%)	1	0/2 (0%)	0
Pain at injection site	0/4 (0%)	0	1/2 (50%)	1
Shoulder pain	0/4 (0%)	0	1/2 (50%)	1
Side pain	1/4 (25%)	1	0/2 (0%)	0
Sweating	0/4 (0%)	0	2/2 (100%)	2
Tremors	1/4 (25%)	1	0/2 (0%)	0
Urinary incontinence	1/4 (25%)	1	0/2 (0%)	0
Vomiting	1/4 (25%)	1	1/2 (50%)	1
Weakness	1/4 (25%)	1	0/2 (0%)	0
Weight loss	1/4 (25%)	1	2/2 (100%)	2
Infections and infestations
Infection	1/4 (25%)	1	0/2 (0%)	0
Renal and urinary disorders
Hematuria	1/4 (25%)	1	0/2 (0%)	0
Urinary frequency	0/4 (0%)	0	1/2 (50%)	1
Urinary retention	1/4 (25%)	1	0/2 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/4 (25%)	1	0/2 (0%)	0
Skin and subcutaneous tissue disorders
Rash	0/4 (0%)	0	2/2 (100%)	3

Limitations/Caveats

Study terminated prematurely due to slow accrual

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.