Clinical Trials /

A Phase I Trial of Vemurafenib and Hydroxychloroquine in Patients With Advanced BRAF Mutant Melanoma

NCT01897116

Description:

This is a Phase I study combining vemurafenib and hydroxychloroquine in the treatment of BRAF V600E+ metastatic melanoma.

Related Conditions:
  • Melanoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

A Phase I Trial of Vemurafenib and Hydroxychloroquine in Patients With Advanced <span class="go-doc-concept go-doc-biomarker">BRAF</span> <span class="go-doc-concept go-doc-keyword">Mutant</span> <span class="go-doc-concept go-doc-disease">Melanoma</span>

Title

  • Brief Title: A Phase I Trial of Vemurafenib and Hydroxychloroquine in Patients With Advanced BRAF Mutant Melanoma
  • Official Title: A Phase I Trial of Vemurafenib and Hydroxychloroquine in Patients With Advanced BRAF Mutant Melanoma
  • Clinical Trial IDs

    NCT ID: NCT01897116

    ORG ID: UPCC 06613

    Trial Conditions

    Melanoma

    Trial Interventions

    Drug Synonyms Arms
    Hydroxychloroquine (HCQ)
    Vemurafenib (VEM)

    Trial Purpose

    This is a Phase I study combining vemurafenib and hydroxychloroquine in the treatment of
    BRAF V600E+ metastatic melanoma.

    Detailed Description

    This study is testing vemurafenib and hydroxychloroquine (HCQ) in the treatment of
    metastatic BRAF V600E+ melanoma. Patients will be getting a known active treatment for their
    disease in combination with HCQ which may help overcome resistance so that responses to
    vemurafenib are more durable.

    Trial Arms

    Name Type Description Interventions

    Eligibility Criteria

    Inclusion Criteria:

    - Patients must be at least 18 years of age.

    - Patients must have histologically confirmed diagnosis of Stege IV metastic melanoma
    positive for BRAF V600E mutation by either the COBAS test or other CLIA approved
    assay.

    - Patients must have a ECOG performance status of 0 or 1.

    - Patients must have the following hematologic, renal and liver function: absolute
    neutrophil count > 1500/mm3, platelets > 100,000/mm3, hemoglobin >9g/dL, creatinine
    2 times the upper limits of normal (ULN), albumin > 2g/dL, total bilirubin 1.5
    mg/dl, ALT and AST 3 times above the upper limits of the institutional norm.

    - Patients must be able to provide written informed consent.

    - Negative serum pregnancy test within 7 days prior to commencement of dosing in
    premenopausal women. Women of non-childbearing potential may be included without
    serum pregnancy test if they are either sugically sterile or have been postmenopausal
    for 1 year.

    Fertile men and women must an effective method of contraception during treatment and for
    at least 6 months after completion of treatment as directed by their physician. Effective
    methods of contraception are defined as those which result in a low failure rate (i.e.,
    less than 1% per year) when used consistenly and correctly (for example implants,
    injectables, combined oral contraception or intra-uterine devices). At the discretion of
    the Investigator, acceptable methods of contraception may include total abstinence in
    cases where the lifestyle of the patient ensures compliance. (Periodic abstinence (e.g.
    calendar, ovulation, sympothermal, postovulation methods) with withdrawal are not
    acceptable methods of contraception.)

    - Patients with treated brain metastases that have been stable for 1 month are
    eligible; patients must be off steroids for 1 week prior to starting study treatment.

    - Any number and type of prior anticancer therapies except BRAF or MEK inhibitors.

    - Patients must have discontinued active immunotherapy (IL-2, interferon, CTLA-4, etc.)
    or chemotherapy at least 4 weeks prior to entering the study and oral targeted
    therapy at least 2 weeks prior to entering the study and have recovered from adverse
    events due to those agents. Patients must not receive any other investigational
    anticancer therapy during the period on study or the four weeks prior to entry, with
    the exception of vaccines.

    Exclusion Criteria:

    - Patients with serious concurrent infection or medical illness, which would jeopardize
    the ability of the patient to receive the treatment outlined in this protocol with
    reasonable safety.

    - Patients who are pregnant and breast-feeding.

    - Patients receiving concurrent therapy for their tumor (i.e.chemotherapeutics or
    investigational agents).

    - Patients with leptomeningeal disease.

    - Patients with a concurrent or prior malignancy within the last 2 years, unless they
    are patients with curatively treated carcinoma-in-situ, or basal cell carcinoma or
    squamous cell carcinoma of the skin. Patients with treated prostate cancer or breast
    cancer for which no concurrent therapy is indicated are eligible for this study.
    Patients who have been free of disease (any prior malignancy) for five years are
    eligible for this study.

    - Due to risk of disease exacerbation patients with porphyria are not eligible.

    - Due to risk of disease exacerbation patients with psoriasis are ineligible unless the
    disease is well controlled and they are under the care of a specialist for the
    disorder who agrees to monitor the patient for exacerbations.

    - Patients receiving cytochrome P450 enzyme-inducing anticonvulsant drugs (EIADs) (i.e.
    phenytoin, carbamazepine, Phenobarbital, primidone, or oxcarbazepine) are ineligible.

    - Patients with previously documented macular degeneration or diabetic retinopathy are
    ineligible.

    - Patients with prior exposure to BRAF or MEK inhibitors are not eligible.

    - Because patients witn immune deficiency are at increased risk of lethal infections
    when treated with bone marrow-suppressive therapy, HIV-positive patients are excluded
    from the study. For patients receiving combination anti-retroviral therapy, the
    potential impact of pharmacokinetic interactions with HCQ and VEM is unknown.
    Appropriate studies may be undertaken in patients with HIV and those receiving
    combination anti-retrovital therapy in the future.

    - History of congenital long QT syndrome or a corrected QTc interval 450 msec at
    baseline.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Number of Adverse Events

    Secondary Outcome Measures

    Trial Keywords