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

NCT02050321 | Terminated Phase 2 Results DMC

• 1 other identifier: 1312167559
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Malignant Melanoma

Outcome Measures

Primary Outcomes (1)

• Rate of Development of cSCC at 6 Months (Biopsy Confirmed).

  6 months post treatment

Secondary Outcomes (1)

• Number of Participants With Adverse Events

  Baseline through 30 Days post Treatment

Study Arms (1)

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.

Drug: Acitretin; Drug: Vemurafenib

Interventions

Acitretin DRUG

A combination of Acitretin and Vemurafenib will be administered to determine if it reduces the incidence of biopsy-confirmed cSCC at 6 months

Also known as: Soriatane

Acitretin and Vemurafenib

Vemurafenib DRUG

A combination of Acitretin and Vemurafenib will be administered to determine if it reduces the incidence of biopsy-confirmed cSCC at 6 months

Also known as: Zelboraf

Acitretin and Vemurafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Arizona: lead

Study Sites (1)

University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Acitretin; Vemurafenib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Terpenes; Pigments, Biological; Biological Factors; Sulfonamides; Amides; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Lee Cranmer
• Organization: University of Arizona Cancer Center

lcranmer@uacc.arizona.edu

520 626-0501

Study Officials

• Lee Cranmer, MD, PhD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2014
• First Posted: January 30, 2014
• Study Start: December 1, 2013
• Primary Completion: December 1, 2014
• Study Completion: July 1, 2015
• Last Updated: December 26, 2018
• Results First Posted: April 19, 2017

Record last verified: 2018-12

Locations

US (1)