Study of Everolimus (RAD001) in Combination With Lenalidomide

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Brief Title

Study of Everolimus (RAD001) in Combination With Lenalidomide

Official Title

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

Brief Summary

      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.
    

Detailed Description

      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.

      An expansion cohort is currently enrolling patients with adenoidcystic carcinoma,
      neuroendocrine and kidney cancer.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

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

Secondary Outcome

 The frequency of achieving a complete plus partial response with the 2 drug combination by dose cohort to be assessed by non-investigational cross sectional imaging after every 2 cycles

Condition

Solid Organ Malignancies

Intervention

Lenalidomide

Study Arms / Comparison Groups

 Lenalidomide combination with everolimus
Description:  Non-randomized study of escalating doses of daily, orally administered lenalidomide in combination with standard doses of everolimus, an orally available mammalian target of rapamycin (mTOR) inhibitor.

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

44

Start Date

September 2010

Completion Date

May 2017

Primary Completion Date

May 2017

Eligibility Criteria

        Inclusion Criteria:

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

          -  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
             study.

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

          -  Patients must have at least one measurable site of disease according to Response
             Evaluation Criteria in Solid Tumors (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 radiation.

          -  Diagnosed with advanced refractory solid malignancies or intolerant of standard
             therapy for the stage of the disease (because there is currently no standard approved
             therapy for adenoidcystic carcinoma, therefore there is no requirement of prior
             therapy for this patient population).

          -  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.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 at study entry.

          -  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 upper limit of normal (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
                  higher

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

          -  All study participants must be registered into the mandatory Revlimid Risk Evaluation
             and Mitigation Strategy (REMS®) program, and be willing and able to comply with the
             requirements of the REMS® program.

          -  Females of reproductive potential must adhere to the scheduled pregnancy testing as
             required in the Revlimid REMS® program.

          -  Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
             test with a sensitivity of at least 50 milli-International Unit (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.

        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.

          -  Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).

          -  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 the cytochrome P450 (CYP450) enzyme(s) are
             provided.

          -  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 ≥ 3 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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Taofeek Owonikoko, PhD/MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01218555

Organization ID

IRB00031088

Secondary IDs

WCI1717-09

Responsible Party

Principal Investigator

Study Sponsor

Emory University

Collaborators

 Celgene

Study Sponsor

Taofeek Owonikoko, PhD/MD, Principal Investigator, Emory University Winship Cancer Institute


Verification Date

March 2018