Clinical Trials /

A Phase II Study of Vemurafenib Combined With Acitretin in Patients With Advanced Melanoma

NCT02050321

Description:

We propose to conduct a phase 2 study to assess whether the addition of acitretin to vemurafenib therapy is able to decrease the rate of cutaneous squamous cell carcinoma (cSCC) development, a known side effect of vemurafenib therapy, in patients with advanced melanoma. Further, we seek a preliminary assessment as to whether the addition of acitretin to vemurafenib enhances the clinical efficacy of this anti-melanoma agent.

Related Conditions:
  • Melanoma
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

A Phase II Study of Vemurafenib Combined With <span class="go-doc-concept go-doc-intervention">Acitretin</span> in Patients With Advanced <span class="go-doc-concept go-doc-disease">Melanoma</span>

Title

  • Brief Title: A Phase II Study of Vemurafenib Combined With Acitretin in Patients With Advanced Melanoma
  • Official Title: A Phase II Study of Vemurafenib Combined With Acitretin in Patients With Advanced Melanoma
  • Clinical Trial IDs

    NCT ID: NCT02050321

    ORG ID: 1312167559

    Trial Conditions

    Malignant Melanoma

    Trial Interventions

    Drug Synonyms Arms
    Acitretin Soriatane Acitretin and Vemurafenib
    Vemurafenib Zelboraf Acitretin and Vemurafenib

    Trial Purpose

    We propose to conduct a phase 2 study to assess whether the addition of acitretin to
    vemurafenib therapy is able to decrease the rate of cutaneous squamous cell carcinoma (cSCC)
    development, a known side effect of vemurafenib therapy, in patients with advanced melanoma.
    Further, we seek a preliminary assessment as to whether the addition of acitretin to
    vemurafenib enhances the clinical efficacy of this anti-melanoma agent.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Acitretin and Vemurafenib Experimental Vemurafenib is self-administered at a dose of 960 mg (four 240 mg tablets) twice daily. The first dose should be taken in the morning and the second dose should be taken in the evening approximately 12 hours later. Each dose can be taken with or without a meal. Acitretin will initially be dosed at 25 mg orally per day with dosing altered every two weeks with a 50 mg dose. Acitretin, Vemurafenib

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically or cytologically confirmed advanced melanoma.

    - BRAF mutation detected by DNA sequencing of exon 15.

    - Age 18 or older.

    - ECOG Performance Status 0-2.

    - Appropriate tumor imaging studies (i.e. CT scan chest, abdomen and pelvis or PET/CT
    scan) performed within 28 days of study registration.

    - Patients with melanoma measurable by RECIST 1.1 criteria will be monitored using this
    system for evidence of disease response/progression.

    - Patients with a known history of brain metastases must have a diagnostic quality MRI
    of the brain or contrasted CT scan of the head performed within 28 days prior to
    registration.

    - Female patients of child bearing capacity must have had 2 negative urine or serum
    pregnancy tests with a sensitivity of at least 25 mIU/mL before receiving the initial
    acitretin prescription. The first test (a screening test) is obtained by the
    prescriber when the decision is made to pursue acitretin therapy. The second
    pregnancy test (a confirmation test) should be done during the first 5 days of the
    menstrual period immediately preceding the beginning of acitretin therapy. The second
    test will be need to be repeated if not performed within 14 days prior to
    registration.

    - Willingness to use at least two forms of contraception during sexual intercourse,
    including at least one form of barrier contraception, for at least 30 days prior to
    receiving the first dose of acitretin AND during the study period, AND up to 3 years
    after receiving the last dose of acitretin.

    - Patients must agree not to consume alcoholic beverages while receiving acitretin and
    for 2 months after cessation of therapy.

    - Electrocardiogram with QTc <450 ms at baseline.

    - Patients must be evaluated for the following within 14 days prior to registration:

    - leukocytes >3,000/mcL

    - absolute neutrophil count >1,500/mcL

    - platelets >100,000/mcL

    - Hemoglobin >9.0 g/dL

    - AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal

    - Alkaline phosphatase <2.5 X institutional upper limit of normal

    - Total bilirubin <1.5 X institutional upper limit of normal

    - Renal function serum creatinine <1.5 mg/dL OR 1.5 x institutional normal;
    alternatively, creatinine clearance as assessed by 24-hour urine collection 60
    ml/min

    - Total cholesterol < 239 mg/dL or < 6.1 mmol/L

    - LDL < 159 mg/d or < 4.1mmol/L

    - HDL > 40 mg/dL or >1.0 mmol/L

    - Serum triglycerides < 199 mg/dL or < 2.2 mmol/L

    - Potassium 3.5-5.5 mMol/L

    - Magnesium 1.7-2.6mg/dL

    - Calcium 8.5-10.6 mg/dL

    Exclusion Criteria:

    - Known hypersensitivity to vemurafenib, acitretin, or vitamin A analogues.

    - Uncontrolled hypertension.

    - Serious and uncontrolled hypertriglyceridemia.

    - Uncontrolled coronary artery disease or active anginal symptoms.

    - Uncontrolled brain metastases.

    - Concomitant malignancies or previous malignancies within the last 5 years, with the
    exception of adequately treated basal or squamous cell carcinoma of the skin,
    carcinoma in situ of the cervix, or low-grade prostate cancer.

    - Myocardial Infarction, Transient Ischemic Attack (TIA), Cerebrovascular Accident
    (CVA) or symptomatic Congestive Heart Failure (CHF) within 6 months of study
    registration.

    - Corrected QTc interval >450ms at baseline, history of congenital long QT syndrome, or
    known and uncorrectable electrolyte abnormalities.

    - History of organ or hematologic transplant.

    - Underlying defined genetic syndrome based on individual or family history
    predisposing to high risk of non-melanoma or melanoma skin cancer as assessed by the
    treating Oncologist.

    - Concurrent use of St John's Wort.

    - Concurrent (or within 60 days prior to acitretin dosing) use of methotrexate or other
    tetracyclines, phenytoin, vitamin A supplements, Tegison (etretinate) or
    progestin-only oral contraceptives.

    - Pregnant or nursing.

    - Receipt of any other investigational agents.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Rate of development of cSCC at 6 months (biopsy confirmed).

    Secondary Outcome Measures

    Adverse Events

    Trial Keywords