Study of RAD001 in Soft Tissue Extremity and/or Retroperitoneal Sarcomas
Condition: Sarcoma
MeSH terms: Sarcoma
Intervention: RAD001
Intervention description: Patients were instructed to take RAD001 in the morning, at the same time each day.
Intervention MeSH terms: Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Soft Tissue; Retroperitoneal; resectable

Summary:

      The goal of this clinical research study is to learn if the study drug RAD001 can stop or
      slow the growth of resectable soft tissue sarcoma. The patient's physical state, their
      symptoms, changes in the size of the tumor, and laboratory findings obtained while on-study
      will help the research team decide if RAD001 is safe and effective in patients with this
      condition. The study drug, RAD001, is made by Novartis Pharmaceuticals Corporation.
    

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