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Uveal MelanomaPhase 1NCT02768766

Intermittent Selumetinib for Uveal Melanoma

A Phase 1 study testing Selumetinib, 100mg, Selumetinib, 125mg and Selumetinib, 150mg in people with Uveal Melanoma, run by Shaheer A. Khan at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The purpose of this study is to find out what effects, good and/or bad, intermittent dosing of the drug Selumetinib will have on subjects with uveal melanoma. Selumetinib is a drug that blocks (or turns off) methyl ethyl ketone (MEK), a protein activated in some uveal melanoma cells. Selumetinib is a MEK inhibitor. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Uveal Melanoma
What is being tested?
Selumetinib, 100mg, Selumetinib, 125mg and Selumetinib, 150mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
3 sitesUnited States
Study dates
28 Feb 2017to 18 Sep 2020
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

  • Histopathologically confirmed diagnosis of metastatic or unresectable uveal melanoma. Note - Documentation of mutation status for uveal melanoma will not be required prospectively given the high rate of GNAQ/11 mutations (>90%) in this population
  • Able to provide informed consent prior to initiation of study
  • Age ≥ 18 years old
  • Measurable indicator lesion by RECIST v1.1
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam.
  • Karnofsky Performance Status ≥ 60% or Eastern Cooperative Oncology Group (ECOG) ≤2
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  • Ability to take oral medications
  • All clinically significant toxicities from prior therapy must be ≤ grade 1 (with the exception of alopecia)
  • Organ and marrow function and laboratory values as follows:
  • Adequate marrow function
  • absolute neutrophil count (ANC) >1500 cells/mm3
  • platelet count >100,000/mm3
  • hemoglobin >9.0g/dL
  • Adequate hepatic function
  • Angiotensin Sensitivity Test/alternative (AST/ALT)<2.5x upper limit of normal if no documented liver disease or <5x upper limit of normal if documented liver disease
  • Total bilirubin <1.5X upper limit of normal unless known diagnosis of Gilbert's disease
  • Alkaline phosphatase <2.5x upper limit of normal if no documented liver disease or <6x upper limit of normal if documented liver or bone disease
  • Creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
  • Negative pregnancy test (serum or urine) for women of child bearing potential
  • The effects of selumetinib on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and 4 weeks after study discontinuation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of selumetinib administration.

Who cannot join

  • Patients who have had chemotherapy or immunotherapy within 4 weeks or radiation therapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
  • Patients who are receiving any other investigational agents concurrently. Palliative radiation therapy will be allowed as long as the patient meets all other eligibility criteria.
  • Have had recent major surgery within a minimum 4 weeks prior to starting study treatment, with the exception of surgical placement for vascular access.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib
  • Every effort must be made to avoid the use of a concomitant medication that can prolong the corrected QT (QTc) interval while receiving selumetinib (hyd-sulfate AZD6244). If the patient cannot discontinue medications that prolong QTc interval while receiving selumetinib, close cardiac monitoring should be performed.
  • Patients with QTc interval >450 msecs or other factors that increase the risk of QTc prolongation or arrhythmic events (ex. Heart failure, hypokalemia, family history of long QT syndrome) including heart failure that meets New York Heart Association (NYHA) class III and IV definitions (see Appendix A) are excluded.
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  • Prior or current cardiomyopathy including but not limited to the following: known hypertrophic cardiomyopathy, known arrhythmogenic right ventricular cardiomyopathy, previous moderate or severe impairment of left ventricular systolic function (LVEF <45% on echocardiography or equivalent on MuGA) even if full recovery has occurred.
  • Atrial fibrillation with a ventricular rate >100 bpm on ECG at rest
  • Baseline Left ventricular ejection fraction (LVEF) below the LLN or <55% measured by echocardiography or institution's lower limit of normal (LLN) for MUGA
  • Severe valvular heart disease
  • Uncontrolled Angina - Canadian Cardiovascular Society grade II-IV despite medical therapy
  • Acute coronary syndrome within 6 months prior to starting treatment
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Pregnant women are excluded from this study because selumetinib may be teratogenic or have abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with selumetinib, breastfeeding should be discontinued if the mother is treated with selumetinib.
  • HIV positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with selumetinib.
  • Prior treatment with a MEK, Ras or Raf inhibitor
  • History of current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED) in the eye unaffected by uveal melanoma; intraocular pressure (IOP) >21mmgHG or uncontrolled glaucoma
  • History of interstitial lung disease or pneumonitis
  • Patients with known Hepatitis B or C
  • Refractory nausea and vomiting, active gastrointestinal disease (e.g. inflammatory bowel disease), or significant bowel resection that would preclude adequate absorption
  • Patients taking vitamin E supplements while on study
  • Have known or suspected brain metastases or spinal cord compression, unless the condition has been asymptomatic, has been treated with surgery and / or radiation, and has been stable for at least 4 weeks prior to the first dose of study medication
  • Any unresolved toxicity ≥ CTCAE Grade 2 from previous anti-cancer therapy, except for alopecia
  • Have evidence of any other significant clinical disorder or laboratory finding that, as judged by the investigator, makes it undesirable for the patient to participate in the study.
  • Patients being actively treated for a secondary malignancy

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Columbia University Medical Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: Multi-Center Phase Ib Study of Intermittent Dosing of the MEK Inhibitor, Selumetinib, in Patients With Advanced Uveal Melanoma Not Previously Treated With a MEK Inhibitor

The purpose of this study is to find out what effects, good and/or bad, intermittent dosing of the drug Selumetinib will have on subjects with uveal melanoma. Selumetinib is a drug that blocks (or turns off) methyl ethyl ketone (MEK), a protein activated in some uveal melanoma cells. Selumetinib is a MEK inhibitor. Blocking MEK may stop the cancer from growing.

Read the detailed description

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, and arises from melanocytes within the choroid plexus of the eye. The development of metastasis is common and occurs in approximately 50% of patients with posterior UM within 15 years of initial diagnosis and treatment. As no effective systemic therapy has yet been identified for this disease, outcomes for metastatic UM are poor with a median survival of 12 months.

There is no FDA approved therapy for patients with advanced UM. Studies have shown that inhibition of the Mitogen-activated protein kinase (MAPK) pathway with the MEK inhibitor selumetinib (hyd-sulfate AZD6244) is an effective therapy for uveal melanoma but despite this treatment, cures are not achieved. Although drugs such as selumetinib have been studied when patients take the treatment every day, research has shown that in some cases, it may be better to use the treatment on an intermittent schedule. Such a strategy may reduce the side effects, allow higher doses of the drug to be used, more completely block the MAPK pathway, and prevent the development of drug resistance mechanisms within the tumor.

Conditions
Uveal Melanoma
Being tested
Selumetinib, 100mg, Selumetinib, 125mg, Selumetinib, 150mg, Selumetinib, 175mg, Selumetinib, 200mg
Keywords
MEK inhibitor, Selumetinib, hyd-sulfate AZD6244, Uveal melanoma, Melanoma
Medical subject headings
Uveal Melanoma, Melanoma

What participants receive

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

  • Selumetinib, 100mgDrug

    Also called hyd-sulfate AZD6244

    100mg, oral capsules, twice daily

    An orally active, small molecule with potential antineoplastic activity. Selumetinib is an ATP-independent inhibitor of mitogen-activated protein kinase kinase (MEK) or MAPK/extracellular-signal-regulated kinase (ERK) kinase) 1 and 2. Inhibition of both MEK1 and 2 by selumetinib prevents the activation of MEK1/2 dependent effector proteins and transcription factors, thereby leading to an inhibition of cellular proliferation in various cancers.

  • Selumetinib, 125mgDrug

    Also called hyd-sulfate AZD6244

    125mg, oral capsules, twice daily

    An orally active, small molecule with potential antineoplastic activity. Selumetinib is an ATP-independent inhibitor of mitogen-activated protein kinase kinase (MEK) or MAPK/extracellular-signal-regulated kinase (ERK) kinase) 1 and 2. Inhibition of both MEK1 and 2 by selumetinib prevents the activation of MEK1/2 dependent effector proteins and transcription factors, thereby leading to an inhibition of cellular proliferation in various cancers.

  • Selumetinib, 150mgDrug

    Also called hyd-sulfate AZD6244

    150mg, oral capsules, twice daily

    An orally active, small molecule with potential antineoplastic activity. Selumetinib is an ATP-independent inhibitor of mitogen-activated protein kinase kinase (MEK) or MAPK/extracellular-signal-regulated kinase (ERK) kinase) 1 and 2. Inhibition of both MEK1 and 2 by selumetinib prevents the activation of MEK1/2 dependent effector proteins and transcription factors, thereby leading to an inhibition of cellular proliferation in various cancers.

  • Selumetinib, 175mgDrug

    Also called hyd-sulfate AZD6244

    175mg, oral capsules, twice daily

    An orally active, small molecule with potential antineoplastic activity. Selumetinib is an ATP-independent inhibitor of mitogen-activated protein kinase kinase (MEK) or MAPK/extracellular-signal-regulated kinase (ERK) kinase) 1 and 2. Inhibition of both MEK1 and 2 by selumetinib prevents the activation of MEK1/2 dependent effector proteins and transcription factors, thereby leading to an inhibition of cellular proliferation in various cancers.

  • Selumetinib, 200mgDrug

    Also called hyd-sulfate AZD6244

    200mg, oral capsules, twice daily

    An orally active, small molecule with potential antineoplastic activity. Selumetinib is an ATP-independent inhibitor of mitogen-activated protein kinase kinase (MEK) or MAPK/extracellular-signal-regulated kinase (ERK) kinase) 1 and 2. Inhibition of both MEK1 and 2 by selumetinib prevents the activation of MEK1/2 dependent effector proteins and transcription factors, thereby leading to an inhibition of cellular proliferation in various cancers.

  • Selumetinib, 225mgDrug

    Also called hyd-sulfate AZD6244

    225mg, oral capsules, twice daily

    An orally active, small molecule with potential antineoplastic activity. Selumetinib is an ATP-independent inhibitor of mitogen-activated protein kinase kinase (MEK) or MAPK/extracellular-signal-regulated kinase (ERK) kinase) 1 and 2. Inhibition of both MEK1 and 2 by selumetinib prevents the activation of MEK1/2 dependent effector proteins and transcription factors, thereby leading to an inhibition of cellular proliferation in various cancers.

Study groups in NCT02768766
Study groupRoleWhat they receive
Dose Level 1: SelumetinibExperimentalSubjects will receive selumetinib (hyd-sulfate AZD6244) orally twice a day for three days followed by four days off in four week cycles at a dose of 100mg.
Receives: Drug: Selumetinib, 100mg
Dose Level 2: SelumetinibExperimentalSubjects will receive selumetinib (hyd-sulfate AZD6244) orally twice a day for three days followed by four days off in four week cycles at a dose of 125mg.
Receives: Drug: Selumetinib, 125mg
Dose Level 3: SelumetinibExperimentalSubjects will receive selumetinib (hyd-sulfate AZD6244) orally twice a day for three days followed by four days off in four week cycles at a dose of 150mg.
Receives: Drug: Selumetinib, 150mg
Dose Level 4: SelumetinibExperimentalSubjects will receive selumetinib (hyd-sulfate AZD6244) orally twice a day for three days followed by four days off in four week cycles at a dose of 175mg.
Receives: Drug: Selumetinib, 175mg
Dose Level 5: SelumetinibExperimentalSubjects will receive selumetinib (hyd-sulfate AZD6244) orally twice a day for three days followed by four days off in four week cycles at a dose of 200mg.
Receives: Drug: Selumetinib, 200mg
Dose Level 6: SelumetinibExperimentalSubjects will receive selumetinib (hyd-sulfate AZD6244) orally twice a day for three days followed by four days off in four week cycles at a dose of 225mg.
Receives: Drug: Selumetinib, 225mg

What is being measured

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

  1. Maximum Tolerated Dose (MTD) of intermittent selumetinib

    MTD is defined as the dose associated with a target probability of dose limiting toxicity (DLT) of 25%. DLT will be assessed over the course of first two cycles of treatment (i.e., 8 weeks) for dose selection for subsequent patient treatment initiation.

    Measured: Up to 8 weeks

Secondary outcomes (6)

  1. Number of adverse events (AEs)

    Number of AE throughout the study to assess the safety and tolerability of intermittent selumetinib

    Measured: Up to 2 years

  2. Number of serious adverse events (SAEs)

    Number of SAE throughout the study to assess the safety and tolerability of intermittent selumetinib

    Measured: Up to 2 years

  3. Number of subjects with Dose Limiting Toxicity (DLT)

    Number of subjects with DLT throughout the study to assess the safety and tolerability of intermittent selumetinib. Toxicity was graded using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v. 4.0). For recurrent adverse events (AEs), the highest reported grade per event per patient was assessed. The DLT observation period was 8 weeks from the initiation of treatment. DLT was defined as any of the following: 1) any serious AE deemed related to the investigational treatment (included grade 1 or 2 ocular toxicity requiring dose reduction); 2) receiving <75% of the planned doses during weeks 1-8; and, 3) death related to the investigational regimen.

    Measured: 8 weeks

  4. Overall Response Rate (ORR)

    The overall response rate (ORR) was defined as a confirmed complete response (CR) (Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm) or partial response (PR) (At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters) according to RECIST 1.1 criteria.

    Measured: Up to 2 years

  5. Progression Free Survival (PFS)

    PFS measured from date of enrollment until the date of progression or death, whichever occurred first.

    Measured: Up to 2 years

  6. Overall Survival (OS)

    OS defined as the time from the date of enrollment to the date of death by any cause.

    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 posted11 May 2016 (estimated)
  2. Study start28 Feb 2017
  3. Primary completion18 Sep 2020
  4. Study completion18 Sep 2020

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
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02768766
Sponsor's protocol ID
AAAQ6999
Status last verified
Aug 2023
First submitted
10 May 2016
Last updated
31 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Carvajal RD, Piperno-Neumann S, Kapiteijn E, Chapman PB, Frank S, Joshua AM, Piulats JM, Wolter P, Cocquyt V, Chmielowski B, Evans TRJ, Gastaud L, Linette G, Berking C, Schachter J, Rodrigues MJ, Shoushtari AN, Clemett D, Ghiorghiu D, Mariani G, Spratt S, Lovick S, Barker P, Kilgour E, Lai Z, Schwartz GK, Nathan P. Selumetinib in Combination With Dacarbazine in Patients With Metastatic Uveal Melanoma: A Phase III, Multicenter, Randomized Trial (SUMIT). J Clin Oncol. 2018 Apr 20;36(12):1232-1239. doi: 10.1200/JCO.2017.74.1090. Epub 2018 Mar 12.

    PubMed 29528792

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Selumetinib, 100mg, Selumetinib, 125mg and Selumetinib, 150mg in people with Uveal Melanoma, run by Shaheer A. Khan at 3 sites 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 25 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: finished, as of the sponsor's last update on 31 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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 (MTD) of intermittent selumetinib (time frame: Up to 8 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 NCT02768766, which also lists 1 linked publication.

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 31 Aug 2023.

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