Brief Title
RAD001 (Everolimus) and Pasireotide (SOM230) LAR in Patients With Advanced Uveal Melanoma
Official Title
A Phase II Study of RAD001 (Everolimus) and Pasireotide (SOM230) LAR in Patients With Advanced Uveal Melanoma
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Number of Participants With Complete Response (CR)
Secondary Outcome
Median Progression Free Survival(PFS)
Condition
Uveal Melanoma
Intervention
RAD001 (Everolimus) and Pasireotide (SOM230) LAR
Study Arms / Comparison Groups
RAD001 and pasireotide LAR
Description: This study will be an open-label, single-arm, phase II study of RAD001 and pasireotide LAR.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
14
Start Date
November 2010
Completion Date
June 2016
Primary Completion Date
June 2016
Eligibility Criteria
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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Michael Postow, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01252251
Organization ID
10-123
Responsible Party
Sponsor
Study Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
Novartis Pharmaceuticals
Study Sponsor
Michael Postow, MD, Principal Investigator, Memorial Sloan Kettering Cancer Center
Verification Date
June 2016