Clinical Trials /

Everolimus With and Without Temozolomide in Adult Low Grade Glioma

NCT02023905

Description:

The purpose of this study is to find out what effects, good and/or bad, everolimus (RAD001, also known as Afinitor®) alone or with temozolomide has on the patient and the patient's low-grade glioma. Everolimus is being investigated as an anticancer agent based on its potential to prevent tumor cells from growing and multiplying. Specifically, there is a protein called mTOR that we think helps many tumors to grow, and everolimus blocks the effect of mTOR. Temozolomide is also an anticancer agent that prevents tumor cells from growing and multiplying. About 159 people total will take part in this study. Patients will be assigned to one of three treatment groups depending on the results of some tests done on their tumor. Each group will have 53 patients in it. 2 groups will receive treatment with everolimus alone, while the third group will receive treatment with both everolimus and temozolomide. In this study, patients will be assigned to one of 3 treatment arms based on two characteristics of their tumor, called "1p/19q" (this is a test of the tumor chromosomes) and "p-PRAS40" (this is a test of a pathway in the tumor called mTOR). If the patient's tumor is 1p/19q intact and p-PRAS40 positive, the patient will be assigned to Treatment Arm 1, and the patient will receive everolimus alone. If the patient's tumor is 1p/19q intact and p-PRAS40 negative, the patient will be assigned to Treatment Arm 2 and the patient will receive everolimus and temozolomide. If the patient's tumor is 1p/19q co-deleted, regardless of the p-PRAS40 result, the patient will be assigned to Treatment Arm 3, and the patient will receive everolimus alone.

Related Conditions:
  • Glioma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Everolimus</span> With and Without <span class="go-doc-concept go-doc-intervention">Temozolomide</span> in Adult Low Grade <span class="go-doc-concept go-doc-disease">Glioma</span>

Title

  • Brief Title: Everolimus With and Without Temozolomide in Adult Low Grade Glioma
  • Official Title: PI3K/mTOR Pathway Activation Selected Phase II Study of Everolimus (RAD001) With and Without Temozolomide in the Treatment of Adult Patients With Supratentorial Low-Grade Glioma
  • Clinical Trial IDs

    NCT ID: NCT02023905

    ORG ID: Novartis- CRAD001CUS225T

    NCI ID: Cancer Center # 131012

    Trial Conditions

    Low Grade Glioma

    WHO Grade II Astrocytomas

    Oligodendrogliomas

    Mixed Oligoastrocytomas

    Trial Interventions

    Drug Synonyms Arms
    Everolimus RAD001, Afinitor Arm 1, Arm 2, Arm 3
    Temozolomide Temodar, TMZ Arm 2

    Trial Purpose

    The purpose of this study is to find out what effects, good and/or bad, everolimus (RAD001,
    also known as Afinitor) alone or with temozolomide has on the patient and the patient's
    low-grade glioma. Everolimus is being investigated as an anticancer agent based on its
    potential to prevent tumor cells from growing and multiplying. Specifically, there is a
    protein called mTOR that we think helps many tumors to grow, and everolimus blocks the
    effect of mTOR. Temozolomide is also an anticancer agent that prevents tumor cells from
    growing and multiplying. About 159 people total will take part in this study. Patients will
    be assigned to one of three treatment groups depending on the results of some tests done on
    their tumor. Each group will have 53 patients in it. 2 groups will receive treatment with
    everolimus alone, while the third group will receive treatment with both everolimus and
    temozolomide. In this study, patients will be assigned to one of 3 treatment arms based on
    two characteristics of their tumor, called "1p/19q" (this is a test of the tumor
    chromosomes) and "p-PRAS40" (this is a test of a pathway in the tumor called mTOR). If the
    patient's tumor is 1p/19q intact and p-PRAS40 positive, the patient will be assigned to
    Treatment Arm 1, and the patient will receive everolimus alone. If the patient's tumor is
    1p/19q intact and p-PRAS40 negative, the patient will be assigned to Treatment Arm 2 and the
    patient will receive everolimus and temozolomide. If the patient's tumor is 1p/19q
    co-deleted, regardless of the p-PRAS40 result, the patient will be assigned to Treatment Arm
    3, and the patient will receive everolimus alone.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Arm 1 Experimental If the tumor is 1p/19q intact, then patients will be further selected by whether or not their tumor demonstrates activation of the PI3K/mTOR pathway. If activation is present, patients will be treated in Arm 1 with single-agent everolimus at 10 mg daily continuously. In all arms, treatment with everolimus will continue for up to 24 cycles, after which patients will be followed with interval MRIs until progression. Everolimus
    Arm 2 Experimental If the tumor is 1p/19q intact, then patients will be further selected by whether or not their tumor demonstrates activation of the PI3K/mTOR pathway. If activation is not present, patients will be treated in Arm 2 with combined everolimus and Temozolomide. Everolimus will be given at 10 mg daily continuously, and Temozolomide will be dosed initially at 150 mg/m2/day for 5 days out of a 28-day cycle. In all arms, treatment with everolimus will continue for up to 24 cycles, after which patients will be followed with interval MRIs until progression. In Arm 2, TMZ will be stopped after 12 cycles. Everolimus, Temozolomide
    Arm 3 Experimental If the tumor is 1p/19q intact, then patients will be further selected by whether or not their tumor demonstrates activation of the PI3K/mTOR pathway. If 1p/19q co-deletion is present, patients will be treated in Arm 3 with single-agent everolimus at 10 mg daily continuously. In all arms, treatment with everolimus will continue for up to 24 cycles, after which patients will be followed with interval MRIs until progression. Everolimus

    Eligibility Criteria

    Inclusion Criteria:

    - Age 18 years

    - KPS 60

    - Adequate bone marrow function as shown by: ANC 1.5 x 109/L, Platelets 100 x
    109/L, Hb 9.0 g/dL;

    - Adequate liver function as shown by: Total serum bilirubin 2.0 mg/dL, ALT and AST
    2.5x ULN, INR 2;

    - Adequate renal function: serum creatinine 1.5 x ULN;

    - Fasting serum cholesterol 300 mg/dL OR 7.75 mmol/L AND fasting triglycerides
    2.5x 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 with
    confirmed reduction of lab values to within eligibility parameters;

    - Signed informed consent prior to any screening procedures

    - Histologically proven supratentorial low-grade glioma at initial diagnosis; pathology
    must have been reviewed by UCSF neuropathology. Eligible low-grade gliomas include:
    astrocytoma, oligodendroglioma and mixed oligoastrocytoma. Pilocytic astrocytomas are
    excluded.

    - Evaluable disease

    - No prior tumor treatment except for surgery at diagnosis

    - Must begin treatment within 120 days of surgical procedure

    - Paraffin-embedded sections of tissue acquired from surgery at the time of diagnosis
    must be available for analysis

    Exclusion Criteria:

    - Currently receiving anticancer therapies or who have received anticancer therapies
    within 4 weeks of the start of everolimus (including chemotherapy, radiation therapy,
    antibody based therapy, etc.);

    - Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g.
    sirolimus, temsirolimus);

    - Known impairment of gastrointestinal (GI) function or GI disease that may
    significantly alter the absorption of oral everolimus;

    - Uncontrolled diabetes mellitus as defined by HbA1c > 8.0% 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;

    - Any severe and/or uncontrolled medical conditions such as: unstable angina pectoris,
    symptomatic congestive heart failure, myocardial infarction 6 months prior to start
    of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically
    significant cardiac disease; symptomatic congestive heart failure of New York heart
    Association Class III or IV; active (acute or chronic) or uncontrolled severe
    infection, liver disease such as cirrhosis, decompensated liver disease, and chronic
    hepatitis (i.e. quantifiable HBV-DNA and/or positive HbsAg, quantifiable HCV-RNA);
    known severely impaired lung function (spirometry and DLCO 50% or less of normal and
    O2 saturation 88% or less at rest on room air); active, bleeding diathesis;

    - Chronic treatment with corticosteroids or other immunosuppressive agents. Topical or
    inhaled corticosteroids are allowed, and treatment with low dose Decadron ( 3mg
    daily) is allowed;

    - Known history of HIV seropositivity;

    - Positive serological test results for hepatitis B

    - Positive serological test result for hepatitis C

    - Recipients of live attenuated vaccines within 1 week of start of everolimus and
    during the study. 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;

    - History of another primary malignancy, with the exceptions of: non-melanoma skin
    cancer, and carcinoma in situ of the cervix, uterus, or breast, unless the patient
    has been disease free for 3 years;

    - History of non-compliance to medical regimens or who are considered potentially
    unreliable or will not be able to complete the entire study;

    - Currently part of or have participated in any clinical investigation with an
    investigational therapeutic drug within 1 month prior to dosing;

    - Pregnant or nursing (lactating) women;

    - Women of child-bearing potential (WOCBP), defined as all women physiologically
    capable of becoming pregnant, who are not willing to use adequate methods of
    contraception during the study and for 8 weeks after the end of treatment.

    - Women are considered post-menopausal and not of child-bearing 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 child-bearing potential.

    - Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate
    contraception, during the study and for 8 weeks after the end of treatment

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Arm 1 & 2 Progression-free survival

    Arm 3 progression-free survival

    Secondary Outcome Measures

    Trial Keywords