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MelanomaPhase 1NCT02068079

A Pilot Study of Trientine With Vemurafenib for the Treatment BRAF Mutated Metastatic Melanoma

A Phase 1 study testing Vemurafenib and Trientine in people with Melanoma, run by Duke University at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The purpose of this study is to evaluate the safety of combination therapy with vemurafenib and trientine in patients with BRAF mutated metastatic melanoma. Vemurafenib is a drug that is currently approved by the United States Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) to treat adult… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma
What is being tested?
Vemurafenib and Trientine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Apr 2014to Nov 2015
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Willing and able to give written informed consent.
  • ECOG performance status ≤ 1
  • Histologic diagnosis of unresectable stage IIIC or stage IV melanoma that is BRAF V600 mutation positive
  • Stable, treated brain metastases are allowed. Stable brain metastases are defined as stable on MRI 4 weeks after the completion of radiation, and currently asymptomatic no longer requiring corticosteroids for 2 weeks prior to the initiation of study drug.
  • Cutaneous tumor deposits that, in the opinion of the investigator are amenable to sequential biopsies for correlative analyses. In addition to these, all patients must have measurable disease (i.e., present with at least one measurable lesion per RECIST, version 1.1).
  • Able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
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  • Required values for initial laboratory tests:
  • WBC ≥ 2000/uL
  • ANC ≥ 1000/uL
  • Platelets ≥ 75 x 103/uL
  • Hemoglobin ≥ 9 g/dL (≥ 80 g/L; may be transfused)
  • Creatinine ≤ 2.0 x ULN
  • AST/ALT ≤ 2.5 x ULN for patients without liver metastasis, ≤ 5 times for liver metastases
  • Bilirubin ≤ 2.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
  • Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 26 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not post-menopausal. Post-menopause is defined as:
  • Amenorrhea ≥ 12 consecutive months without another cause, or
  • For women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level ≥ 35 mIU/mL.
  • Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential.
  • WOCBP must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours.
  • Men of fathering potential must be using an adequate method of contraception to avoid conception throughout the study [and for up to 26 weeks after the last dose of investigational product] in such a manner that the risk of pregnancy is minimized.

Who cannot join

  • Prior treatment with a BRAF or MEK inhibitor for metastatic melanoma (treatment in the adjuvant setting is allowed)
  • Any other malignancy form which the patient has been disease-free for less than 2 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or DCIS. Patients with prior malignancies that are not considered to be an active problem may be enrolled at the discretion of the investigator, regardless of time frame.
  • Women of childbearing potential (WOCBP), defined above in Section 4.1, who:
  • are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 26 weeks after cessation of study drug, or
  • have a positive pregnancy test at baseline, or
  • are pregnant or breastfeeding.
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  • Anti-cancer therapy within 28 days prior to starting on therapy
  • Any serious or unstable pre-existing medical conditions psychiatric disorders, or other conditions that could interfere with the subject's safety, obtaining informed consent, or compliance with study procedures.
  • Known history of Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection which will be allowed).
  • A history or evidence of cardiovascular risk including any of the following:
  • A QTc interval ≥ 500 ms at screening
  • A history or evidence of current clinically significant uncontrolled arrhythmias; Exception: Subjects with atrial fibrillation controlled for > 30 days prior to randomization are eligible.
  • A history (within 6 months prior to randomization) of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty
  • A history or evidence of current ≥Class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines
  • Treatment refractory hypertension defined as a blood pressure of systolic> 150 mmHg and/or diastolic > 100 mm Hg which cannot be controlled by antihypertensive therapy;
  • Patients with intra-cardiac defibrillators or permanent pacemakers;
  • A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) including:
  • Presence of predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, uncontrolled diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes)
  • Females who are nursing
  • A known diagnosis of Wilson's disease.
  • Patients with clinical symptoms consistent with active gastritis.
  • Patients with a condition that, in the opinion of the investigator, would interfere with the absorption of oral medication will be excluded from the study.
  • Patients requiring iron supplementation will be excluded.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Duke University Medical Center

    Durham, North Carolina, 27710

Other trials in United States

About this study

The purpose of this study is to evaluate the safety of combination therapy with vemurafenib and trientine in patients with BRAF mutated metastatic melanoma.

Vemurafenib is a drug that is currently approved by the United States Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) to treat adult patients with melanoma that has spread to other parts of the body or cannot be removed by surgery. It can only be used in patients whose cancer has a change (mutation) in the "BRAF" gene.

Read more

Preclinical data suggests that use of a copper chelator (reducer) is a strategy to block cellular signaling activity which would result in anti-tumor effects (slow tumor growth). Trientine is a copper chelator and is FDA approved for the treatment of Wilson's disease (a disease of copper metabolism) and is generally well tolerated. It works by binding to copper to help remove it from the body. Trientine is not FDA approved for the treatment of melanoma and its use in this study is investigational. "Investigational" means the study drug is still being tested in research studies.

All patients will receive vemurafenib at 960mg PO twice daily with continuous dosing in combination with trientine in escalating doses. The dose of trientine will depend on what portion of the study.

In order to participate in the study, patients must test positive for the change (mutation) in the BRAF gene.

Conditions
Melanoma
Being tested
Vemurafenib and Trientine
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Vemurafenib and TrientineDrug

Study groups in NCT02068079
Study groupRoleWhat they receive
Vemurafenib and TrientineOtherNot described
Receives: Drug: Vemurafenib and Trientine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose

    Maximum Tolerated Dose is defined as the highest dose level in which ≤1 of 6 patients experience a dose limiting toxicity.

    Measured: 1 Cycle (4 Weeks)

Secondary outcomes (7)

  1. Overall Response

    The number of complete and partial responses using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee v 1.1

    Measured: 1 year

  2. Progression Free Survival (PFS)

    PFS is defined as the time from study enrollment to disease progression or death due to any cause, whichever comes first.

    Measured: 2 years

  3. Overall Survival (OS)

    OS is defined from enrollment to death due to any cause.

    Measured: 2 years

  4. The change in phosphorylated Erk kinase activity relative to total Erk kinase activity

    Measured: Pre-treatment; two weeks into combination therapy (day 15), and at the time of disease progression while still on combination therapy, up to 2 years

  5. The change in phosphorylated MEK kinase activity relative to total MEK kinase activity

    Measured: Pre-treatment; two weeks into combination therapy (day 15), and at the time of disease progression while still on combination therapy, up to 2 years

  6. The change in the expression of the copper transporter CTR1

    Change will be measured as the percent change compared to the baseline status

    Measured: Up to 2 years

  7. Incidence of hyperproliferative skin lesions, specifically cutaneous squamous cell carcinomas and keratoacanthomas

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Feb 2014 (estimated)
  2. Study startApr 2014
  3. Primary completionNov 2015
  4. Study completionNov 2015

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02068079
Sponsor's protocol ID
Pro00045015
Status last verified
Jan 2019
First submitted
19 Feb 2014
Last updated
30 Jan 2019
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vemurafenib and Trientine in people with Melanoma, run by Duke University 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 20 inclusion and 23 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: withdrawn, as of the sponsor's last update on 30 Jan 2019. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Maximum Tolerated Dose (time frame: 1 Cycle (4 Weeks)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02068079.

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 30 Jan 2019; AzTrials last refreshed its copy on 7 Nov 2026.

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