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A Single-arm, Open Label Phase II Study of RAD001 in Soft Tissue Extremity and/or Retroperitoneal Sarcomas

Phase 2
18 Years
Not Enrolling

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Trial Information

A Single-arm, Open Label Phase II Study of RAD001 in Soft Tissue Extremity and/or Retroperitoneal Sarcomas

A single-arm, open label, proof of principle phase II study exploring the efficacy of RAD001
in resectable soft tissue sarcomas either in the extremities, trunk or retroperitoneum.
Patients with resectable sarcomas as detailed below were to have a core biopsy for molecular
markers prior to therapy with RAD001 10mg PO daily x 2 weeks. Within 7-14 days of the end of
therapy with RAD001, the patients were to be brought to surgery for definitive resection or,
should they be candidates for neoadjuvant radiation, would have 6 16 gauge core biopsies
taken percutaneously or using image guidance. Pharmacodynamic markers as detailed in the
objectives were to be assessed in the laboratory.

Patients were to be numbered sequentially from 1 to 40, or more if there were patients that
dropped out due to drug toxicity, with the goal of achieving 40 patients in accrual for
evaluation of the pre- and post-treatment tumor samples for Pharmacodynamic assays.

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,

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Pharmacodynamics (PD) Markers

Outcome Description:

PD markers of RAD001 on downstream signaling pathways in patients with sarcomas: p70S6K, S6-RP, P-AKT, cleaved PARP and PCNA by Western blot, quantitative multiplex assays and immunohistochemical studies measured pre and post the 2 week treatment of RAD001. Patients were to be separated into two groups, responders and non responders based on PD results and downstream up regulation of the referenced pathways. Mean fractional inhibition of each PD marker for the responding and non-responding groups were to be calculated. Our planned analysis was for 40 participants.

Outcome Time Frame:

Pre and post the 2 week treatment

Safety Issue:


Principal Investigator

Jonathan S. Zager, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

January 2010

Completion Date:

October 2011

Related Keywords:

  • Sarcoma
  • Soft Tissue
  • Retroperitoneal
  • resectable
  • Sarcoma



H. Lee Moffitt Cancer Center and Research InstituteTampa, Florida  33612