Clinical Trials /

Vemurafenib in Combination With Everolimus or Temsirolimus With Advanced Cancer

NCT01596140

Description:

The goal of this clinical research study is to find the highest tolerable dose of vemurafenib that can be given in combination with either everolimus or temsirolimus. The safety of these drug combinations will also be studied. Vemurafenib is designed to block BRAF inside the cancer cells, which is a mutation that is involved in cancer cell growth. Temsirolimus and everolimus are designed to block the growth of cancer cells, which may cause cancer cells to die.

Related Conditions:
  • Cancer
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Vemurafenib in Combination With <span class="go-doc-concept go-doc-intervention">Everolimus</span> or <span class="go-doc-concept go-doc-intervention">Temsirolimus</span> With Advanced <span class="go-doc-concept go-doc-disease">Cancer</span>

Title

  • Brief Title: Vemurafenib in Combination With Everolimus or Temsirolimus With Advanced Cancer
  • Official Title: A Phase I Dose-Escalation Study of the BRAF Inhibitor Vemurafenib (Zelboraf) in Combination With an mTOR Inhibitor, Everolimus (Afinitor) or Temsirolimus (Torisel), in Subjects With Advanced Cancer
  • Clinical Trial IDs

    NCT ID: NCT01596140

    ORG ID: 2012-0153

    NCI ID: NCI-2012-00789

    Trial Conditions

    Advanced Cancer

    Solid Tumor

    Trial Interventions

    Drug Synonyms Arms
    Vemurafenib Zelboraf, PLX4032, RO5185426 Vemurafenib + Oral Everolimus, Vemurafenib + Intravenous Temsirolimus
    Everolimus Afinitor, RAD001 Vemurafenib + Oral Everolimus
    Temsirolimus Temodar Vemurafenib + Intravenous Temsirolimus

    Trial Purpose

    The goal of this clinical research study is to find the highest tolerable dose of
    vemurafenib that can be given in combination with either everolimus or temsirolimus. The
    safety of these drug combinations will also be studied.

    Vemurafenib is designed to block BRAF inside the cancer cells, which is a mutation that is
    involved in cancer cell growth.

    Temsirolimus and everolimus are designed to block the growth of cancer cells, which may
    cause cancer cells to die.

    Detailed Description

    Study Drug Administration:

    If you are found to be eligible to take part in this study, your doctor will decide whether
    you will receive either everolimus or temsirolimus

    You will be assigned to a dose level of vemurafenib based on when you join this study. Up to
    5 dose levels of vemurafenib will be tested. Up to 6 participants will be enrolled at each
    dose level. The first group of participants will receive the lowest dose level. Each new
    group will receive a higher dose than the group before it, if no intolerable side effects
    were seen. This will continue until the highest tolerable dose of vemurafenib is found.

    Study Drug Administration:

    You will take 3 vemurafenib tablets in the morning and 3 tablets in the evening.You will
    take it every day during each 28-day study cycle. You will take vemurafenib in combination
    with either 1 tablet of everolimus every day of each cycle or you will receive temsirolimus
    by vein over 30-60 minutes on Days 1, 8, 15, and 22 of each cycle.

    You will receive a dosing diary to record ONLY the date and times when you did NOT take a
    scheduled dose of the study drug. You should bring this diary and any used or unused study
    drug bottles to your next study visit (even empty bottles must be returned).

    Study Visits:

    At all study visits, you will be asked about any drugs you may be taking and if you have had
    any side effects from them.

    On Days 1 and 15 of Cycle 1 and Day 1 of Cycle 6:

    - You will have a physical exam, including measurement of your vital signs.

    - Your performance status will be recorded.

    - Blood (about 3 teaspoons) will be drawn for routine tests.

    - You will have an ECG (Day 15 only)

    On Day 1 of Cycles 2 and 5:

    - You will have a physical exam, including measurement of your vital signs.

    - Your performance status will be recorded.

    - Blood (about 3 teaspoons) will be drawn for routine tests.

    - You will have an ECG.

    - Your skin will be checked.

    - You will have a CT scan or MRI scan to check the status of the disease (Cycle 5 only).

    On Day 1 of Cycle 3:

    - You will have a physical exam, including measurement of your vital signs.

    - Your performance status will be recorded.

    - Blood (about 3 teaspoons) will be drawn for routine tests.

    - You will have an ECG.

    - You will have a CT scan or MRI scan to check the status of the disease.

    On Day 1 of Cycle 4:

    - You will have a physical exam, including measurement of your vital signs.

    - Your performance status will be recorded.

    - Blood (about 3 teaspoons) will be drawn for routine tests.

    - You will have an ECG.

    - You will have a head and neck exam to check the status of the disease.

    On Day 1 of Cycle 7:

    - You will have a physical exam, including measurement of your vital signs.

    - Your performance status will be recorded.

    - Blood (about 3 teaspoons) will be drawn for routine tests.

    - You will have a CT scan or MRI scan to check the status of the disease.

    - You will have a head and neck exam to check the status of the disease.

    On Day 1 of Cycles 8 and beyond:

    - You will have a physical exam, including measurement of your vital signs.

    - Your performance status will be recorded.

    - Blood (about 3 teaspoons) will be drawn for routine tests.

    After Cycle 7, every 12 weeks:

    - You will have an ECG.

    - You will have a head and neck exam to check the status of the disease.

    - Your skin will be checked.

    On Day 1 of every 2 cycles:

    - You will have a CT scan or MRI scan to check the status of the disease.

    Length of Study:

    You may continue taking the study drugs for as long as the doctor thinks it is in your best
    interest. You will no longer be able to take the study drugs if the disease gets worse, if
    intolerable side effects occur, or if you are unable to follow study directions.

    Your participation on the study will be over once you have completed the follow-up.

    End of Study Drug Dosing Visit:

    Once you are no longer taking the study drug, you will have a study visit. At this visit:

    You will be asked about any drugs you may be taking and if you have had any side effects
    from them.

    - You will have a physical exam, including measurement of your vital signs.

    - Your performance status will be recorded.

    - Blood (about 3 teaspoons) will be drawn for routine tests.

    - You will have an ECG.

    - You will have a CT scan or MRI scan to check the status of the disease.

    - Your skin will be checked.

    Safety Follow-Up Visit:

    If you leave the study for any reason other than the disease getting worse, you will have a
    follow-up visit about 28 days after your last dose. At this visit:

    - You will be asked about any drugs you may be taking and if you have had any side
    effects from them.

    - You will have an ECG.

    - Your skin will be checked.

    - You will have a head and neck exam to check the status of the disease.

    Follow-Up:

    Every 3 months after the last dose of study drug (for up to 12 months) you will be contacted
    by phone and asked about any new drugs you may be taking. This should take less than 5
    minutes. This follow up may be during a regularly scheduled clinic visit.

    Participant Responsibilities:

    - Take the study drug as instructed by the study staff.

    - Keep your study appointments. If you cannot keep an appointment, reschedule as soon as
    you know that you will miss the appointment.

    - Tell your doctor or study staff about any side effects, doctor visits, or
    hospitalizations that you may have.

    - Keep the study drug in a safe place, for your use only, and away from children. It must
    be stored at room temperature but not warmer than 77 degrees F (25 degrees Celsius).

    - Complete your diaries as instructed

    - While on this study, you cannot take part in any other research project without
    approval from your doctor.

    This is an investigational study. Vemurafenib is FDA-approved for metastatic melanoma. Its
    use in other types of cancer is investigational. Everolimus and temsirolimus are FDA
    approved kidney cancer. The combination of these drugs is investigational.

    Up to 114 participants will be enrolled in this study. All will take part at MD Anderson.

    Trial Arms

    Name Type Description Interventions
    Vemurafenib + Oral Everolimus Experimental Vemurafenib starting dose 720 mg orally twice day (morning/evening) for 28-day cycle plus Oral Everolimus starting dose 5 mg daily. Vemurafenib, Everolimus
    Vemurafenib + Intravenous Temsirolimus Experimental Vemurafenib starting dose 720 mg orally twice day (morning/evening) for 28-day cycle plus Intravenous Temsirolimus starting dose 15 mg daily on Days 1, 8, 15, and 22 of each cycle. Vemurafenib, Temsirolimus

    Eligibility Criteria

    Inclusion Criteria:

    1. Confirmation of BRAF mutation-positive malignancy is required for selection of
    patients for vemurafenib therapy

    2. Measurable or non-measurable disease by RECIST 1.1.

    3. Patients with advanced cancer should be refractory to standard therapy, relapsed
    after standard therapy, or have no standard therapy available that improves survival
    by at least three months.

    4. Patients must be at least 3 weeks past receiving cytotoxic therapy and at least 5
    half-lives after their previous treatment or 3 weeks, whichever is shorter, after
    biologic therapy. Patients may receive palliative radiotherapy immediately or during
    treatment provided that not all target lesions are radiated.

    5. ECOG performance status </= 2 (Karnofsky >/= 60%; Lansky Score >/= 50).

    6. Patients must have normal organ and marrow function defined as: absolute neutrophil
    count >/=1,000/mL; platelets >/=50,000/mL; creatinine < 2.0; total bilirubin < 2.0;
    ALT(SGPT) </= 3 X ULN; Exception for patients with liver metastasis: ALT(SGPT) </= 5
    X ULN.

    7. Women of childbearing potential and men must agree to use adequate contraception
    (hormonal or barrier method of birth control; abstinence) prior to study entry, for
    the duration of study participation, and for 30 days after the last dose.

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

    Exclusion Criteria:

    1. Patients with uncontrolled concurrent illness, including but not limited to: ongoing
    or active infection requiring hospitalization; psychiatric illness/social situations
    that would limit compliance with study requirements.

    2. Exclusion of patients with creatinine >2.0 and bilirubin > 2.0.

    3. Pregnant or lactating women.

    4. Patients with a history of bone marrow transplant within the previous two years.

    5. Patients with a known hypersensitivity to any of the components of the drug products.

    6. Patients with major surgery within 30 days prior to entering the study.

    7. Patients with a baseline QTc > 500 ms.

    8. Patients who are unable to swallow pills.

    Minimum Eligible Age: N/A

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Maximum Tolerated Dose (MTD) of Combination Vemurafenib

    Secondary Outcome Measures

    Tumor Response

    Trial Keywords

    Vemurafenib

    Everolimus

    Afinitor

    RAD001

    temsirolimus

    BRAF gene mutation

    solid tumor

    relapsed BRAF mutation positive malignant melanoma

    refractory BRAF mutation positive malignant melanoma