Intervention: Everolimus
Trial phase: Phase 2
ATC code: L01EG02 | L04AA18
SMILES: COC1CC2CCC(C)C(O)(O2)C(=O)C(=O)N2CCCCC2C(=O)OC(C(C)CC2CCC(OCCO)C(OC)C2)CC(=O)C(C)C=C(C)C(O)C(OC)C(=O)C(C)CC(C)C=CC=CC=C1C
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 2
Group description: RAD001 was administered orally as once daily dose of 10 mg PO daily x 2 weeks (14 X 10 mg tablets) continuously from study day 1 until the end of therapy (2 weeks later) or unacceptable toxicity.
Eligibility criteria:
Inclusion Criteria:

Have a resectable primary or recurrent sarcoma according to diagnostic imaging criteria (computed tomography [CT] and/or magnetic resonance imaging [MRI]) that has not been previously irradiated.
Primary/recurrent or persistent sarcoma must be amenable to core biopsy for pre RAD001 pharmacodynamic studies
World Health Organization (WHO) performance status ≤ 2
Adequate bone marrow function shown by: absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, Platelets ≥ 100 x 10^9/L, hemoglobin (Hb) >9 g/dL
Adequate liver function shown by: serum bilirubin ≤ 1.5 x upper limit of normal (ULN); alanine transaminase (ALT) and aspartic transaminase (AST) ≤ 2.5x ULN
International Normal Ratio (INR) and partial thromboplastin time (PTT) ≤1.5. (Anticoagulation 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 randomization.)
Adequate renal function: serum creatinine ≤ 1.5 x ULN
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, patient can only be included after initiation of appropriate lipid lowering medication.
Signed informed consent
Patients with resectable soft tissue extremity or retroperitoneal sarcomas amenable to pre-treatment core biopsy
Biopsy proven surgically resectable retroperitoneal sarcomas of any histologic grade

Exclusion Criteria:

Currently receiving anticancer therapies or have received anticancer therapies within 4 weeks of the start of study drug. Note: Primary/recurrent/ persistent sarcoma must not have been previously treated with radiation. Primary/recurrent or persistent sarcoma must not have been treated within 4 weeks of the start of RAD001 with other chemotherapeutic agents
Have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
Receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
Should not receive immunization with attenuated live vaccines within 1 week of study entry or during study period
Brain or leptomeningeal metastases
Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin.
Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: Symptomatic congestive heart failure of New York Heart Association (NYHA) Class III or IV; unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease; severely impaired lung function as defined as spirometry and diffusing lung capacity oxygenation (DLCO) that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air; uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN; active (acute or chronic) or uncontrolled severe infections; liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
Known history of human immunodeficiency virus (HIV) seropositivity
Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001
Patients with an active, bleeding diathesis
Females who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of RAD001)
Received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus).
Known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients
History of noncompliance to medical regimens
Unwilling or unable to comply with the protocol
Cutaneous sarcomas or sarcomas where neoadjuvant chemotherapy or radiation may be indicated in the treatment plan
Sarcomas must be deemed fully resectable by pre-treatment imaging
No evidence of distant disease