Malignant MelanomaPhase 2NCT02050321
A Phase II Study of Vemurafenib Combined With Acitretin in Patients With Advanced Melanoma
A Phase 2 study testing Acitretin and Vemurafenib in people with Malignant Melanoma, run by University of Arizona at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Melanoma
- What is being tested?
- Acitretin and Vemurafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2013to Jul 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Arizona Cancer Center
Tucson, Arizona, 85724
About this study
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
- Being tested
- Acitretin, Vemurafenib
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcitretinDrug
Also called Soriatane
A combination of Acitretin and Vemurafenib will be administered to determine if it reduces the incidence of biopsy-confirmed cSCC at 6 months
VemurafenibDrug
Also called Zelboraf
A combination of Acitretin and Vemurafenib will be administered to determine if it reduces the incidence of biopsy-confirmed cSCC at 6 months
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Acitretin; Drug: Vemurafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Development of cSCC at 6 Months (Biopsy Confirmed).
Measured: 6 months post treatment
Secondary outcomes (1)
Number of Participants With Adverse Events
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
Measured: Baseline through 30 Days post Treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2014 (estimated)
- Study startDec 2013
- Primary completionDec 2014
- Study completionJul 2015
Why it stopped: Pharmaceutical company pulled support for the trial.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Malignant MelanomaStudies of the same condition, open and under way.
- More trials run by University of ArizonaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lee Cranmer, MD, PhD, Principal investigator, University of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02050321
- Sponsor's protocol ID
- 1312167559
- Status last verified
- Dec 2018
- First submitted
- 24 Jan 2014
- Last updated
- 26 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Vemurafenib Combined With Acitretin in Patients With Advanced Melanoma
- ClinicalTrials.gov ID
- NCT02050321
- Acronym / sponsor ID
- 1312167559
- Conditions
- Malignant Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Pharmaceutical company pulled support for the trial.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Study start
- Dec 2013
- Primary completion
- Dec 2014 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 30 Jan 2014 (estimated)
- Results
- Posted 19 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Acitretin and Vemurafenib | Experimental | Drug: Acitretin, Drug: VemurafenibVemurafenib 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcitretinAlso: SoriataneA combination of Acitretin and Vemurafenib will be administered to determine if it reduces the incidence of biopsy-confirmed cSCC at 6 months | Drug | Acitretin and Vemurafenib |
| VemurafenibAlso: ZelborafA combination of Acitretin and Vemurafenib will be administered to determine if it reduces the incidence of biopsy-confirmed cSCC at 6 months | Drug | Acitretin and Vemurafenib |
Primary outcome
Rate of Development of cSCC at 6 Months (Biopsy Confirmed).
Time frame: 6 months post treatment
1 secondary outcome
Number of Participants With Adverse Events
Time frame: Baseline through 30 Days post Treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lee Cranmer, MD, PhD principal investigator
University of Arizona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Acitretin and Vemurafenib in people with Malignant Melanoma, run by University of Arizona at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Development of cSCC at 6 Months (Biopsy Confirmed). (time frame: 6 months post treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Dec 2018.