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Phase I Study of Everolimus (RAD001) in Combination With Lenalidomide in Patients With Advanced Solid Malignancies Enriched for Renal Cell Carcinoma

Phase 1
18 Years
Open (Enrolling)
Solid Organ Malignancies

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Trial Information

Phase I Study of Everolimus (RAD001) in Combination With Lenalidomide in Patients With Advanced Solid Malignancies Enriched for Renal Cell Carcinoma

The purpose of this study is to study the combination of two anticancer drugs, everolimus
(RAD001) and lenalidomide in patients whose cancer is no longer responding to standard
treatment or patients who are unable to tolerate the standard treatment for their cancer.
The investigators seek to establish the safety of taking these two medications together and
to determine the appropriate doses of the two drugs when given together as well as identify
potential side effects when the drugs are administered together.

Another purpose of this study is to find out if the medication works for the patient's kind
of cancer and side effects of the combination of RAD001 and lenalidomide by looking at the
patient's response to the treatment. The investigators want to find out what effects, good
or bad, the drugs have on the patient's cancer.

This study will also look at specific substances called biomarkers in the patient's blood
and in the tumor tissue which are involved in the growth of tumor cells and determine if the
levels of these biomarkers are related to the patient's response to treatment or development
of side effects.

Inclusion Criteria:

- Subjects must meet the following inclusion/exclusion criteria to be eligible for the

- Ability to understand and willingness to voluntarily sign an informed consent form.

- Histologic or cytologic confirmation of a solid malignancy

- Age ≥18 years at the time of signing the informed consent form. Because no dosing or
adverse event data are currently available on the use of everolimus in combination
with lenalidomide in patients <18 years of age, children are excluded from this

- Able to adhere to the study visit schedule and other protocol requirements.

- Patients must have at least one measurable site of disease according to RECIST
criteria that has not been previously irradiated. If the patient has had previous
radiation to the marker lesion(s), there must be evidence of progression since the

- Diagnosed with advanced refractory solid malignancies or intolerant of standard
therapy for the stage of the disease

- All previous cancer therapy, including radiation, hormonal therapy and surgery, must
have been discontinued at least 4 weeks prior to treatment in this study. A minimum
of 6 weeks treatment break is required in case of nitrosoureas or mitomycin C.

- ECOG performance status of 0 - 2 at study entry (see Appendix A).

- Able to receive prophylactic anticoagulation with aspirin, warfarin or low molecular
weight heparin when required for lenalidomide administration

- 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.

- Laboratory test results within these ranges:

- Absolute neutrophil count 1500 ≥ /mm³

- Platelet count ≥ 100,000/mm³

- Hb ≥9 g/dL

- Creatinine within institutional limits of normal or Creatinine clearance ≥ 60
ml/min/m2 if elevated creatinine

- Total bilirubin < 2.0 mg/dL or < 1.5.0 x ULN for the institution whichever is

- AST (SGOT) and ALT (SGPT) < 2.x ULN or < 5 x ULN if hepatic metastases are

- All study participants must be registered into the mandatory RevAssist® program, and
be willing and able to comply with the requirements of RevAssist®.

- Females of childbearing potential (FCBP)† must have a negative serum or urine
pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to
and again within 24 hours of prescribing lenalidomide (prescriptions must be filled
within 7 days) and must either commit to continued abstinence from heterosexual
intercourse or begin TWO acceptable methods of birth control, one highly effective
method and one additional effective method AT THE SAME TIME, at least 28 days before
she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing.
Men must agree to use a latex condom during sexual contact with a FCBP even if they
have had a successful vasectomy. See Appendix B: Risks of Fetal Exposure, Pregnancy
Testing Guidelines and Acceptable Birth Control Methods.

Exclusion Criteria:

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements including signing the informed consent form.

- Pregnant or breast feeding females. (Lactating females must agree not to breast feed
while taking lenalidomide).

- Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study.

- Use of any other experimental drug or therapy within 28 days of baseline.

- Known hypersensitivity to thalidomide or everolimus (including other rapamycins,
sirolimus and temsirolimus).

- The development of erythema nodosum if characterized by a desquamating rash while
taking thalidomide or similar drugs.

- Prior treatment with lenalidomide or everolimus

- Concurrent use of other anti-cancer agents or treatments.

- Patients known to be positive for HIV or infectious hepatitis, type B or C requiring
active therapy. Patients on combination antiviral therapy are ineligible because of
the potential for pharmacokinetic interactions with everolimus and or lenalidomide.
In addition, these patients are at increased risk of lethal infections when treated
with marrow-suppressive therapy. Appropriate studies will be undertaken in this
patient population.

- Symptomatic brain metastasis. Patients with treated brain metastasis must be
completely weaned off of steroid therapy for at least 14 days prior to starting
protocol therapy

- Patients receiving chronic, systemic treatment with corticosteroids or another
immunosuppressive agent. Topical or inhaled corticosteroids are allowed.

- Patients should not receive immunization with attenuated live vaccines within one
week of study entry or during study period

- Diagnosed venous thromboembolic disease within the preceding 6 months (patient on
full dose or prophylactic anticoagulation are eligible)

- Patients receiving any medications or substances that are inhibitors or inducers of
CYP450 enzyme(s) are ineligible. Lists of excluded medications and substances known
or with the potential to interact with theCYP450 enzyme(s) are provided in Appendix

- History of other malignancies except: (i) adequately treated basal or squamous cell
carcinoma of the skin; (ii) curatively treated, a) in situ carcinoma of the uterine
cervix, b) prostate cancer, or c) superficial bladder cancer; or (iii) other
curatively treated solid tumor with no evidence of disease for ≥ 5 years

- Patients, who have had a major surgery or significant traumatic injury within 4 weeks
of start of study drug, patients who 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

- Patients with an active, bleeding diathesis

Type of Study:


Study Design:

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

Outcome Measure:

The maximum doses of both drugs that can be administered without inducing dose limiting toxicity (DLT) in ≥33% of the treated patient cohort.

Outcome Time Frame:

Within the first 28 days for DLT and throughout the duration of the study for safety.

Safety Issue:


Principal Investigator

Taofeek Owonikoko, PhD/MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Emory University Winship Cancer Institute


United States: Institutional Review Board

Study ID:




Start Date:

September 2010

Completion Date:

December 2015

Related Keywords:

  • Solid Organ Malignancies
  • kidney cancer
  • adenoidcystic cancer
  • Neoplasms



Emory University Winship Cancer Institute Atlanta, Georgia  30322