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

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

  • ORG STUDY ID: 1312167559
  • NCT ID: NCT02050321

Conditions

  • Malignant Melanoma

Interventions

DrugSynonymsArms
AcitretinSoriataneAcitretin and Vemurafenib
VemurafenibZelborafAcitretin and Vemurafenib

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.

Trial Arms

NameTypeDescriptionInterventions
Acitretin and VemurafenibExperimentalVemurafenib 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of Development of cSCC at 6 Months (Biopsy Confirmed).
Time Frame:6 months post treatment
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Number of Participants With Adverse Events
Time Frame:Baseline through 30 Days post Treatment
Safety Issue:
Description:The study period during which all AEs must be reported begins after informed consent is obtained and initiation of study treatment and ends 30 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier. All adverse events will be classified using either the MedDRA term or NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Terminated
Lead Sponsor:University of Arizona

Last Updated

December 26, 2018