RAD001 (Everolimus) and Pasireotide (SOM230) LAR in Patients With Advanced Uveal Melanoma

• Sponsor: Memorial Sloan Kettering Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01252251
• Collaborator: Novartis Pharmaceuticals (Industry)
• Enrollment: 14
• Location: 1
• Arm: 1
• Duration (Months): 67
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to find out what effects, good and/or bad, the drugs everolimus and pasireotide have on the patient and on melanoma. Pasireotide is also called SOM-230. Pasireotide is an experimental drug and is not approved by the Food and Drug Administration. Everolimus is also called RAD001. Everolimus is approved for use in the U.S. for kidney cancer. Everolimus is not approved for treatment of melanomas, but early studies show that it may help some patients with melanoma.

Condition or Disease	Intervention/Treatment	Phase
Uveal Melanoma	Drug: RAD001 (Everolimus) and Pasireotide (SOM230) LAR	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of RAD001 (Everolimus) and Pasireotide (SOM230) LAR in Patients With Advanced Uveal Melanoma
• Study Start Date: Nov 1, 2010
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RAD001 and pasireotide LAR This study will be an open-label, single-arm, phase II study of RAD001 and pasireotide LAR.	Drug: RAD001 (Everolimus) and Pasireotide (SOM230) LAR; Patients will be treated with SOM-230 (pasireotide) LAR 60mg IM once every 28 days and with RAD001 (Everolimus) 10mg PO daily. Each cycle is 28 days. An optional biopsy may be requested required after weeks of therapy. The biopsy may be performed between days 28 and 42.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Complete Response (CR) [at 16 weeks]

   For patients with metastatic uveal melanoma treated with RAD001 and pasireotide LAR.

2. Number of Participants With Partial Response (PR) [at 16 weeks]

   For patients with metastatic uveal melanoma treated with RAD001 and pasireotide LAR.

3. Number of Participants With Stable Disease (SD) [at 16 weeks]

   For patients with metastatic uveal melanoma treated with RAD001 and pasireotide LAR.

Secondary Outcome Measures

1. Median Progression Free Survival(PFS) [Up to 3 years]

2. Safety and Toxicity in This Patient Population. [16 weeks]

   Safety assessments will consist of monitoring and recording all adverse events, including serious adverse events, the regular monitoring of hematology (including glycosylated hemoglobin and coagulation parameters), blood chemistry (including fasting glucose, thyroid function tests, GH, IGF-1 and prolactin), urinalysis, regular monitoring of vital signs, echocardiography, ECGs, and body weight. Toxicity will be assessed using the NCI-CTC for Adverse Events, version 4.0 (CTCAEv4.0,

3. Median Overall Survival (OS) [Up to 3 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed metastatic uveal melanoma.

• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > or = to 20 mm with conventional techniques or as > or = to 10 mm with spiral CT scan.

• Patients may have had any number of prior therapies, but cannot have previously been treated with a somatostatin analogue or an mTOR inhibitor. At least 3 weeks must have elapsed since the last dose of systemic therapy. At least 6 weeks must have elapsed if the last regimen included BCNU or mitomycin C. At least 3 months must have elapsed if the last regimen included an anti-CTLA4 antibody. If the last regimen included an anti-CTLA4 antibody, radiographic disease progression since this therapy must be documented.

• Age > or = to 18 years. Because no dosing or adverse event data are currently available on the use of RAD001 and SOM230 in patients <18 years of age, children are excluded from this study but will be eligible for future pediatric trials, if applicable.

• Life expectancy of greater than 3 months.

• ECOG performance status 0 or 1.

• Patients must have normal organ and marrow function as defined below:

• leukocytes > or = to 3,000/mcL

• absolute neutrophil count > or = to 1,500/mcL

• platelets > or = to 100,000/mcL

• hemoglobin > or = to 9.0 g/dL not requiring transfusions within the past 2 weeks

• total bilirubin < 1.5 X institutional upper limit of normal

• AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional upper limit of normal

• Creatinine ≤ 1.5 X institutional upper limit of normal or creatinine clearance less than 60 ml/min

• Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication.

• INR ≤1.5. (Anticoagulation is allowed if target INR ≤ 1.5 on a stable dose of warfarin or on a stable dose of LMW heparin for >2 weeks at time of study initiation).

• Women of childbearing potential must have a negative serum pregnancy test within 14 days of the administration of the first study treatment. Women must not be lactating. Both men and women of childbearing potential must be advised of the importance of using effective birth control measures during the course of the study. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study.

• Ability to understand and the willingness to sign a written informed consent document.

• Evidence of disease progression, as determined by the investigator.

Exclusion Criteria:

• Patients may not be receiving any other investigational agents.

• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases. Treated brain metastases must have been stable for at least 2 months.

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to RAD001 or SOM230.

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or bleeding, severely impaired lung function, or psychiatric illness/social situations that would limit compliance with study requirements.

• Pregnant women are excluded from this study because RAD001 and SOM230 are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants, breast-feeding should be discontinued.

• Patients with the presence of active or suspected acute or chronic uncontrolled infection or with a history of immunocompromise, including a positive HIV test result (ELISA and Western blot). The safety of a potentially immunosuppressive drug like everolimus is not proven in patients with HIV. HBV DNA and HCV RNA PCR testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection (see Section 8.0 and hepatitis B/C risk factor screening form.

• Baseline QTc > 450 ms.

• Patients with risk factors for torsades de pointes, including uncorrected hypokalemia, uncorrected hypomagnesemia, family history of long QT syndrome, clinically significant/symptomatic bradycardia, high-grade AV block, autonomic neuropathy (including that caused by diabetes or Parkinson's disease, uncontrolled hypothyroidism, cirrhosis, or the use of concomitant medications known to prolong the QT interval.

• Patients with a history of syncope, family history of idiopathic sudden death, a history of sustained or clinically significant cardiac arrhythmias, symptomatic congestive heart failure (NYHA Class III or IV), unstable angina pectoris, sustained ventricular tachycardia, ventricular fibrillation, advanced heart block, or a history of acute myocardial infarction within the six months preceding enrollment .

• No concomitant anti-cancer chemotherapy or other systemic drugs. Palliative radiation therapy will be allowed as long as the patient meets all other eligibility criteria.

• Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption.

• Chronic treatment with systemic steroids or another immunosuppressive agent.

• Patients should not receive immunization with attenuated live vaccines during study period or within 1 week of study entry. Close contact with those who have received attenuated live vaccines should be avoided during treatment with RAD001. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines.

• Patients with prior or concurrent malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, or any other cancer from which the patient has been disease free for five years.

• Patients with a fasting plasma glucose > 1.5 ULN. Note: At the principle investigator's discretion, non-eligible patients can be re-screened after adequate medical therapy has been instituted.

• Patients with symptomatic cholelithiasis.

• Patients who have a history of alcohol or drug abuse in the 6 month period prior to receiving treatment with pasireotide or RAD001.

• History of liver disease, such as cirrhosis or chronic active hepatitis B and C.

• Presence of Hepatitis B surface antigen (HbsAg).

• Presence of Hepatitis C antibody test (anti-HCV).

• History of, or current alcohol misuse/abuse within the past 12 months.

• Known gallbladder or bile duct disease, acute or chronic pancreatitis.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• Memorial Sloan Kettering Cancer Center
• Novartis Pharmaceuticals

Investigators

• Principal Investigator: Michael Postow, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Memorial Sloan Kettering Cancer Center

Publications

None provided.

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT01252251
• Other Study ID Numbers: 10-123
• First Posted: Dec 2, 2010
• Last Update Posted: Aug 1, 2017
• Last Verified: Jun 1, 2016

• Keywords provided by Memorial Sloan Kettering Cancer Center: PASIREOTIDE (SOM230); RAD001 (EVEROLIMUS); eye; 10-123
• Additional relevant MeSH terms: Melanoma; Uveal Neoplasms; Everolimus; Pasireotide

Study Results

Participant Flow

Recruitment Details	Protocol Open to Accrual 11/30/2010, Protocol Closed to Accrual 8/11/2015, Primary Completion Date 6/13/2016, Recruitment location is the medical clinic

Arm/Group Title	RAD001 and Pasireotide LAR
Arm/Group Description	This study will be an open-label, single-arm, phase II study of RAD001 and pasireotide LAR. RAD001 (Everolimus) and Pasireotide (SOM230) LAR: Patients will be treated with SOM-230 (pasireotide) LAR 60mg IM once every 28 days and with RAD001 (Everolimus) 10mg PO daily. Each cycle is 28 days. An optional biopsy may be requested required after weeks of therapy. The biopsy may be performed between days 28 and 42.
Period Title: Overall Study
STARTED	14
COMPLETED	13
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	RAD001 and Pasireotide LAR
Arm/Group Description	This study will be an open-label, single-arm, phase II study of RAD001 and pasireotide LAR. RAD001 (Everolimus) and Pasireotide (SOM230) LAR: Patients will be treated with SOM-230 (pasireotide) LAR 60mg IM once every 28 days and with RAD001 (Everolimus) 10mg PO daily. Each cycle is 28 days. An optional biopsy may be requested required after weeks of therapy. The biopsy may be performed between days 28 and 42.
Overall Participants	14
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	8 57.1%
Male	6 42.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	13 92.9%
Not Hispanic or Latino	0 0%
Unknown or Not Reported	1 7.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	13 92.9%
More than one race	0 0%
Unknown or Not Reported	1 7.1%
Region of Enrollment (Count of Participants)
United States	14 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Complete Response (CR)
Description	For patients with metastatic uveal melanoma treated with RAD001 and pasireotide LAR.
Time Frame	at 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001 and Pasireotide LAR
Arm/Group Description	This study will be an open-label, single-arm, phase II study of RAD001 and pasireotide LAR. RAD001 (Everolimus) and Pasireotide (SOM230) LAR: Patients will be treated with SOM-230 (pasireotide) LAR 60mg IM once every 28 days and with RAD001 (Everolimus) 10mg PO daily. Each cycle is 28 days. An optional biopsy may be requested required after weeks of therapy. The biopsy may be performed between days 28 and 42.
Measure Participants	13
Participants Evaluated	13 92.9%
Complete Response	0 0%

2. Primary Outcome

Title	Number of Participants With Partial Response (PR)
Description	For patients with metastatic uveal melanoma treated with RAD001 and pasireotide LAR.
Time Frame	at 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001 and Pasireotide LAR
Arm/Group Description	This study will be an open-label, single-arm, phase II study of RAD001 and pasireotide LAR. RAD001 (Everolimus) and Pasireotide (SOM230) LAR: Patients will be treated with SOM-230 (pasireotide) LAR 60mg IM once every 28 days and with RAD001 (Everolimus) 10mg PO daily. Each cycle is 28 days. An optional biopsy may be requested required after weeks of therapy. The biopsy may be performed between days 28 and 42.
Measure Participants	13
Participants Evaluated	13 92.9%
Partial Response	0 0%

3. Primary Outcome

Title	Number of Participants With Stable Disease (SD)
Description	For patients with metastatic uveal melanoma treated with RAD001 and pasireotide LAR.
Time Frame	at 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001 and Pasireotide LAR
Arm/Group Description	This study will be an open-label, single-arm, phase II study of RAD001 and pasireotide LAR. RAD001 (Everolimus) and Pasireotide (SOM230) LAR: Patients will be treated with SOM-230 (pasireotide) LAR 60mg IM once every 28 days and with RAD001 (Everolimus) 10mg PO daily. Each cycle is 28 days. An optional biopsy may be requested required after weeks of therapy. The biopsy may be performed between days 28 and 42.
Measure Participants	13
Count of Participants [Participants]	7 50%

4. Secondary Outcome

Title	Median Progression Free Survival(PFS)
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001 and Pasireotide LAR
Arm/Group Description	This study will be an open-label, single-arm, phase II study of RAD001 and pasireotide LAR. RAD001 (Everolimus) and Pasireotide (SOM230) LAR: Patients will be treated with SOM-230 (pasireotide) LAR 60mg IM once every 28 days and with RAD001 (Everolimus) 10mg PO daily. Each cycle is 28 days. An optional biopsy may be requested required after weeks of therapy. The biopsy may be performed between days 28 and 42.
Measure Participants	13
Median (Full Range) [weeks]	16

5. Secondary Outcome

Title	Safety and Toxicity in This Patient Population.
Description	Safety assessments will consist of monitoring and recording all adverse events, including serious adverse events, the regular monitoring of hematology (including glycosylated hemoglobin and coagulation parameters), blood chemistry (including fasting glucose, thyroid function tests, GH, IGF-1 and prolactin), urinalysis, regular monitoring of vital signs, echocardiography, ECGs, and body weight. Toxicity will be assessed using the NCI-CTC for Adverse Events, version 4.0 (CTCAEv4.0,
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001 and Pasireotide LAR
Arm/Group Description	This study will be an open-label, single-arm, phase II study of RAD001 and pasireotide LAR. RAD001 (Everolimus) and Pasireotide (SOM230) LAR: Patients will be treated with SOM-230 (pasireotide) LAR 60mg IM once every 28 days and with RAD001 (Everolimus) 10mg PO daily. Each cycle is 28 days. An optional biopsy may be requested required after weeks of therapy. The biopsy may be performed between days 28 and 42.
Measure Participants	13
At least 1 dose reduction due to toxicity	7 50%
No dose reduction due to toxicity	6 42.9%

6. Secondary Outcome

Title	Median Overall Survival (OS)
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RAD001 and Pasireotide LAR
Arm/Group Description	This study will be an open-label, single-arm, phase II study of RAD001 and pasireotide LAR. RAD001 (Everolimus) and Pasireotide (SOM230) LAR: Patients will be treated with SOM-230 (pasireotide) LAR 60mg IM once every 28 days and with RAD001 (Everolimus) 10mg PO daily. Each cycle is 28 days. An optional biopsy may be requested required after weeks of therapy. The biopsy may be performed between days 28 and 42.
Measure Participants	13
Median (Full Range) [months]	11

Adverse Events

Time Frame	28 weeks
Arm/Group Title	RAD001 and Pasireotide LAR
Arm/Group Description	This study will be an open-label, single-arm, phase II study of RAD001 and pasireotide LAR. RAD001 (Everolimus) and Pasireotide (SOM230) LAR: Patients will be treated with SOM-230 (pasireotide) LAR 60mg IM once every 28 days and with RAD001 (Everolimus) 10mg PO daily. Each cycle is 28 days. An optional biopsy may be requested required after weeks of therapy. The biopsy may be performed between days 28 and 42.
All Cause Mortality
	RAD001 and Pasireotide LAR
	Affected / at Risk (%)	# Events
Total	0/13 (0%)
Serious Adverse Events
	RAD001 and Pasireotide LAR
	Affected / at Risk (%)	# Events
Total	6/13 (46.2%)
Gastrointestinal disorders
Abdominal pain	1/13 (7.7%)
Dysphagia	1/13 (7.7%)
Mucositis oral	1/13 (7.7%)
General disorders
Fatigue	1/13 (7.7%)
Hepatobiliary disorders
Acute kidney injury	2/13 (15.4%)
Infections and infestations
Lung infection	1/13 (7.7%)
Nervous system disorders
Dizziness	1/13 (7.7%)
Other (Not Including Serious) Adverse Events
	RAD001 and Pasireotide LAR
	Affected / at Risk (%)	# Events
Total	13/13 (100%)
Blood and lymphatic system disorders
Anemia	1/13 (7.7%)
Eye disorders
Blurred vision	1/13 (7.7%)
Gastrointestinal disorders
Diarrhea	8/13 (61.5%)
Mucositis oral	7/13 (53.8%)
Nausea	5/13 (38.5%)
Constipation	2/13 (15.4%)
Abdominal pain	1/13 (7.7%)
Anal mucositis	1/13 (7.7%)
Dry mouth	1/13 (7.7%)
Dysphagia	1/13 (7.7%)
Oral pain	1/13 (7.7%)
Vomiting	1/13 (7.7%)
General disorders
Fatigue	4/13 (30.8%)
Non-cardiac chest pain	2/13 (15.4%)
Fever	1/13 (7.7%)
Investigations
Cholesterol high	11/13 (84.6%)
White blood cell decreased	9/13 (69.2%)
CPK increased	8/13 (61.5%)
Platelet count decreased	8/13 (61.5%)
Alkaline phosphatase increased	5/13 (38.5%)
Neutrophil count decreased	5/13 (38.5%)
Alanine aminotransferase increased	3/13 (23.1%)
Aspartate aminotransferase increased	3/13 (23.1%)
Serum amylase increased	3/13 (23.1%)
Lipase increased	2/13 (15.4%)
Creatinine increased	1/13 (7.7%)
Lymphocyte count decreased	1/13 (7.7%)
Metabolism and nutrition disorders
Hyperglycemia	13/13 (100%)
Hypertriglyceridemia	11/13 (84.6%)
Hyponatremia	9/13 (69.2%)
Hypophosphatemia	6/13 (46.2%)
Hypoalbuminemia	4/13 (30.8%)
Hypokalemia	3/13 (23.1%)
Hyperkalemia	2/13 (15.4%)
Hypercalcemia	2/13 (15.4%)
Musculoskeletal and connective tissue disorders
Chest wall pain	1/13 (7.7%)
Pain in extremity	1/13 (7.7%)
Nervous system disorders
Dizziness	2/13 (15.4%)
Headache	2/13 (15.4%)
Psychiatric disorders
Insomnia	1/13 (7.7%)
Respiratory, thoracic and mediastinal disorders
Cough	4/13 (30.8%)
Sore throat	1/13 (7.7%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	2/13 (15.4%)
Dry skin	2/13 (15.4%)
Erythema multiforme	1/13 (7.7%)
Pruritus	1/13 (7.7%)
Rash acneiform	1/13 (7.7%)
Vascular disorders
Hot flashes	1/13 (7.7%)

Limitations/Caveats

[Not Specified]

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.