Clinical Trials /

Everolimus in Patients With Advanced Solid Malignancies With TSC1, TSC2, NF1, NF2, or STK11 Mutations



The purpose of this research study is to look at participants with solid tumor malignancies and specific mutations respond to treatment with everolimus.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:



Phase 2

Trial Eligibility


<span class="go-doc-concept go-doc-intervention">Everolimus</span> in Patients With Advanced Solid Malignancies With <span class="go-doc-concept go-doc-biomarker">TSC1</span> and <span class="go-doc-concept go-doc-biomarker">TSC2</span> <span class="go-doc-concept go-doc-keyword">Mutations</span>


  • Brief Title: Everolimus in Patients With Advanced Solid Malignancies With TSC1 and TSC2 Mutations
  • Official Title: Phase II Study of Everolimus in Patients With Advanced Solid Malignancies With TSC1 and TSC2 Mutations
  • Clinical Trial IDs

    NCT ID: NCT02352844

    ORG ID: 201502067

    Trial Conditions

    Solid Malignancy

    Solid Tumor

    Trial Interventions

    Drug Synonyms Arms
    Everolimus RAD001, Afinitor, Votubia Arm 1 (everolimus)

    Trial Purpose

    The purpose of this research study is to look at participants with solid tumor malignancies
    and specific mutations respond to treatment with everolimus.

    Detailed Description

    Cancer is a molecularly heterogeneous disease comprised of complex genomic alterations in
    common and overlapping pathways. Somatic inactivating mutations in tuberous sclerosis
    complex 1 (TSC1) gene were recently identified as potential markers of response to mTOR
    therapy. Everolimus is an oral derivative of rapamycin. At the cellular and molecular level,
    everolimus acts as a signal transduction inhibitor, and selectively inhibits mTOR. We
    hypothesize that everolimus will exhibit clinical activity in solid malignancies harboring
    TSC1 and TSC2 mutations.

    Trial Arms

    Name Type Description Interventions
    Arm 1 (everolimus) Experimental Everolimus is an oral drug which will be administered on an outpatient basis at a dose of 10 mg daily on a 28-day cycle. Everolimus

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically confirmed diagnosis of advanced (metastatic, recurrent, or
    unresectable) cancer with mutations in TSC1 and/or TSC2 for which no standard of care
    option exists.

    - Measurable disease defined as lesions that can be accurately measured in at least one
    dimension (longest diameter to be recorded) as >10 mm with CT scan, as >20 mm by
    chest x-ray, or >10 mm with calipers by clinical exam.

    - Prior therapy (chemotherapy, radiation therapy, and surgery) is allowed if completed
    at least 2 weeks prior to registration and if all treatment-related toxicities are

    - At least 18 years of age.

    - ECOG performance status 2

    - Normal bone marrow and organ function as defined below:

    - Leukocytes > 3,000/mcL

    - Absolute neutrophil count > 1,500/mcL

    - Platelets > 100,000/mcL

    - Hemoglobin > 9.0 g/dL

    - Total serum bilirubin 2.0 x IULN

    - AST(SGOT)/ALT(SGPT) 2.5 x IULN ( 5.0 x IULN in patients with liver

    - Serum creatinine 1.5 x IULN OR creatinine clearance > 45 mL/min/1.73 m^2 for
    patients with creatinine levels above institutional normal

    - Fasting cholesterol 300 mg/dL OR 7.75 mmol/L AND fasting triglycerides 2.5
    x IULN. NOTE: In case one or both of these thresholds are exceeded, the patient
    can only be included after initiation of appropriate lipid lowering medication

    - Able to swallow tablets.

    - Women of childbearing potential, defined as all women physiologically capable of
    becoming pregnant, must use highly effective methods of contraception during the
    study and for 8 weeks after. Women are considered post-menopausal and not of
    childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea
    with an appropriate clinical profile (e.g., age appropriate, history of vasomotor
    symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy)
    or tubal ligation at least six weeks prior to randomization. In the case of
    oophorectomy alone, only when the reproductive status of the woman has been confirmed
    by follow-up hormone level assessment is she considered not of childbearing

    - Male patients whose sexual partner(s) are women of childbearing potential must agree
    to use adequate contraception during the study and for 8 weeks after the end of

    - Able to understand and willing to sign an IRB approved written informed consent
    document (or that of legally authorized representative, if applicable)

    Exclusion Criteria:

    - A history of other malignancy 3 years previous with the exception of basal cell or
    squamous cell carcinoma of the skin which were treated with local resection only or
    carcinoma in situ of the cervix.

    - Taking an investigational agent within 4 weeks of initiation of everolimus.

    - Symptomatic brain metastases. Known brain metastases are allowed if asymptomatic and
    previously treated.

    - A history of allergic reactions attributed to compounds of similar chemical or
    biologic composition to everolimus or other agents used in the study.

    - Known impairment of GI function or GI disease that may significantly alter the
    absorption of oral everolimus.

    - Currently taking CYP3A4 inhibitors or inducers (such as the antiepileptic drugs
    phenytoin, carbamazepine, or phenobarbital; cyclosporine; grapefruit or its juice;
    Seville oranges; starfruit; or St. John's wort)

    - Chronic treatment with corticosteroids or other immunosuppressive agents. Topical or
    inhaled corticosteroids are allowed.

    - Received live attenuated vaccine within 1 week of start of everolimus (i.e.
    intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever,
    varicella, and TY21a typhoid vaccines).

    - Uncontrolled diabetes mellitus defined as HbA1c > 8% despite adequate therapy.
    Patients with a known history of impaired fasting glucose or diabetes mellitus may be
    included; however, blood glucose and antidiabetic treatment must be monitored closely
    throughout the trial and adjusted as necessary.

    - Uncontrolled intercurrent illness including, but not limited to, ongoing or active
    infection, symptomatic congestive heart failure of NYHA class III or IV, active
    coronary artery disease, unstable angina pectoris, cardiac arrhythmia, myocardia
    infraction 6 months prior to start of everolimus, uncontrolled hypertension
    (systolic pressure > 150 mmHg or diastolic pressure > 90 mmHg), uncontrolled seizure
    disorder, liver disease such as cirrhosis, decompensated liver disease, active and
    chronic hepatitis, known severely impaired lung function (spirometry and DLCO 50% or
    less of normal and 02 saturation 88% or less at rest on room air), active bleeding
    diathesis, or psychiatric illness/social situations that would limit compliance with
    study requirements.

    - Pregnant and/or breastfeeding. Patient must have a negative pregnancy test within 14
    days of study entry.

    - Known HIV-positivity on combination antiretroviral therapy because of the potential
    for pharmacokinetic interactions with everolimus. In addition, these patients are at
    increased risk of lethal infections when treated with marrow-suppressive therapy.
    Appropriate studies will be undertaken in patients receiving combination
    antiretroviral therapy when indicated.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Response rate (RR)

    Secondary Outcome Measures

    Mutations associated with therapeutic response

    Genetic changes associated with disease progression

    Trial Keywords