Clinical Trials /

Everolimus for Cancer With TSC1 or TSC2 Mutation

NCT02201212

Description:

In this research study, the investigators are evaluating the clinical benefit of everolimus in cancer patients with inactivating TSC1 or TSC2 mutations or activating MTOR mutations. This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug called everolimus to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is being studied. It also means that the FDA (the U.S. Food and Drug Administration) has not yet approved everolimus for your type of cancer. Everolimus is a drug that may stop cancer cells from growing by blocking an important factor (mTOR) involved in the growth of cells. This drug has been used in treatment for other cancers and is approved by the Food and Drug Administration for treatment of several types of cancer, including renal cell carcinoma. Treatment with this drug has been associated with responses in some patients whose cancers had mutations in TSC1 or TSC2. The investigators think that patients whose tumors have mutations in TSC1 or TSC2 may have a good chance of responding to treatment with drugs like everolimus.

Related Conditions:
  • Cancer
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Everolimus</span> for <span class="go-doc-concept go-doc-disease">Cancer</span> With <span class="go-doc-concept go-doc-biomarker">TSC1</span> or <span class="go-doc-concept go-doc-alteration">TSC2 Mutation</span>

Title

  • Brief Title: Everolimus for Cancer With TSC1 or TSC2 Mutation
  • Official Title: A Phase II Trial of Everolimus for Cancer Patients With Inactivating Mutations in TSC1 or TSC2 or Activating MTOR Mutations
  • Clinical Trial IDs

    NCT ID: NCT02201212

    ORG ID: 14-229

    NCI ID: CRAD001MUS217T

    Trial Conditions

    TSC1

    TSC2

    Tuberous Sclerosis Complex

    MTOR

    Trial Interventions

    Drug Synonyms Arms
    Everolimus Afinitor, Zortress, Afinitor Disperz, RAD001 Everolimus

    Trial Purpose

    In this research study, the investigators are evaluating the clinical benefit of everolimus
    in cancer patients with inactivating TSC1 or TSC2 mutations or activating MTOR mutations.

    This research study is a Phase II clinical trial, which tests the safety and effectiveness
    of an investigational drug called everolimus to learn whether the drug works in treating a
    specific cancer. "Investigational" means that the drug is being studied. It also means that
    the FDA (the U.S. Food and Drug Administration) has not yet approved everolimus for your
    type of cancer.

    Everolimus is a drug that may stop cancer cells from growing by blocking an important factor
    (mTOR) involved in the growth of cells. This drug has been used in treatment for other
    cancers and is approved by the Food and Drug Administration for treatment of several types
    of cancer, including renal cell carcinoma. Treatment with this drug has been associated with
    responses in some patients whose cancers had mutations in TSC1 or TSC2. The investigators
    think that patients whose tumors have mutations in TSC1 or TSC2 may have a good chance of
    responding to treatment with drugs like everolimus.

    Detailed Description

    Patients who fulfill eligibility criteria will be entered into the trial.The participant
    will be given a study drug-dosing calendar for each treatment cycle. Each treatment cycle
    lasts 28 days (4 weeks), during which time the participant will be taking the study drug
    orally (by mouth) once daily. The diary will also include special instructions for taking
    the study drug. In addition to the administration of the study drugs the participant will be
    asked to return to the clinic at various time points so that additional exams can be
    performed. These study visits may last as long as 2 hours.

    Trial Arms

    Name Type Description Interventions
    Everolimus Experimental Everolimus Fixed doses orally once a day per each 28 day cycle Participants will stay on study as long as they do not progress for a maximum of 24 months. Tumor assessments will be performed after every 2 cycles for as long as they are on study. Everolimus

    Eligibility Criteria

    Inclusion Criteria: Participants must meet the following criteria on screening examination
    to be eligible to participate in the study:

    - Participants must have histologically confirmed advanced malignancy that is either
    metastatic and/or unresectable and/or recurrent, with confirmed inactivating
    mutations in TSC1 or TSC2, or activating mutations in MTOR, identified in any
    CLIA-certified laboratory. All genetic findings must be reviewed by the study PI, Dr.
    David Kwiatkowski, prior to study entry.

    - Biopsy of a primary or metastatic lesion must have been performed within the past two
    years. Sufficient pathologic material must be available to enable whole exome
    sequencing at the time of study entry.

    - Participants must have measurable disease, defined as at least one lesion that can be
    accurately measured in at least one dimension (longest diameter to be recorded) as
    20 mm with conventional techniques or as 10 mm with spiral CT scan. See section 10
    for the evaluation of measureable disease.

    - Participants may have received any number of prior therapies, from 0 to > 10, but
    prior treatment with PI3-kinase or mTOR inhibitors is not permitted.

    - Age 18 years.

    - ECOG performance status <2 (see Appendix A).

    - Participants must have normal organ and marrow function as defined below:

    - Leukocytes 3,000/mcL

    - Absolute neutrophil count 1,500/mcL

    - Platelets 100,000/mcL

    - Hemoglobin 9.0 gr/dL

    - Total bilirubin 1.5 ULN

    - AST (SGOT)/ALT (SGPT) 2.5 X institutional upper limit of normal. Patients with
    confirmed liver metastases are permitted to have AST/ALT at levels 5X the
    institutional upper limit of normal.

    - Creatinine 1.5 X the institutional upper limit of normal.

    - Total cholesterol < 300 mg/dL

    - Triglycerides < 250 mg/dL

    - The effects of everolimus on the developing human fetus are unknown. For this reason
    and because anti-neoplastic agents are known to be teratogenic, women of
    child-bearing potential and men must agree to use adequate contraception (hormonal or
    barrier method of birth control; abstinence) prior to study entry and for the
    duration of study participation. Should a woman become pregnant or suspect she is
    pregnant while participating in this study, she should inform her treating physician
    immediately.

    - Ability to understand and the willingness to sign a written informed consent
    document.

    - Participants who achieve either a partial response or stable disease 4 months must
    agree to undergo a tumor biopsy, if safe and feasible, at the time of progressive
    disease while on study drug everolimus.

    Exclusion Criteria:Participants who exhibit any of the following conditions at screening
    will not be eligible for admission into the study.

    - Participants who have had any of the following:

    - chemotherapy in the previous 2 weeks (6 weeks for nitrosoureas or mitomycin C)

    - radiotherapy within 3 weeks

    - investigational agents within 3 weeks prior to entering the study

    - patients who have not recovered from significant (in the opinion of the investigator)
    adverse events due to previous agents administered.

    - Child-Pugh B or C hepatic impairment. Patients with a history of hepatitis or
    significant exposure risk should be tested for hepatitis B and C with serologic
    markers: HBsAg, HBs Ab, HBcoreIgG Ab, HCV Ab. Patients with active hepatitis B or C
    are excluded.

    - Any prior exposure to any PI3 kinase or mTOR inhibitor agent.

    - Participants may not be receiving any other research study agents.

    - Uncontrolled brain or leptomeningeal metastases, including patients who continue to
    require glucocorticoids for brain or leptomeningeal metastases. Asymptomatic or
    treated brain metastases are acceptable.

    - History of allergic reactions attributed to compounds of similar chemical or biologic
    composition to everolimus.

    - A list of prohibited medications on study are listed in Section 5.5

    - Chronic treatment with corticosteroids or other immunosuppressive therapy.

    - 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.

    - Pregnant women are excluded from this study because everolimus has the potential for
    teratogenic or abortifacient effects. Because there is an unknown but potential risk
    of adverse events in nursing infants secondary to treatment of the mother with
    everolimus, breastfeeding should be discontinued if the mother is treated with
    everolimus. These potential risks may also apply to other agents used in this study.

    - Individuals with a recent history of a different malignancy are ineligible except for
    the following circumstances: 1) Individuals with a history of other malignancies are
    eligible if they have been disease-free for at least 3 years OR are deemed by the
    investigator to be at low risk for recurrence of that malignancy; 2) Individuals with
    the following cancers are eligible if diagnosed and treated within the past 3 years:
    cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.

    - Individuals with known HIV infection are excluded from this study as combination
    antiretroviral therapy could potentially result in significant pharmacokinetic
    interactions with everolimus. In addition, these individuals are at increased risk of
    lethal infections due to the immunosuppressive effects of mTOR inhibition.

    - Patients who have received live attenuated vaccines within 1 week of start of
    Everolimus. Patient should also avoid close contact with others who have received
    live attenuated vaccines. Examples of live attenuated vaccines include intranasal
    influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and
    TY21a typhoid vaccines.

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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Objective Response Rate

    Secondary Outcome Measures

    Duration of Response Rate

    Progression-free Survival Rate

    Overall Survival Rate

    Toxicity Rate

    Trial Keywords

    TSC1

    TSC2

    Tuberous Sclerosis Complex

    MTOR