AzTrials
AzTrials

Gastrointestinal Stromal Tumor (GIST)Phase 1NCT03158103

A Study of MEK162 (Binimetinib) in Combination With Pexidartinib in Patients With Advanced Gastrointestinal Stromal Tumor (GIST)

A Phase 1 study testing MEK162 and Pexidartinib in people with Gastrointestinal Stromal Tumor (GIST), run by Memorial Sloan Kettering Cancer Center at 1 site 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 test the safety and tolerability of the combination of pexidartinib and MEK162. This study tests different doses of pexidartinib in combination with different doses of MEK162 to see which dose combination of these drugs is safe and best tolerated in people. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Gastrointestinal Stromal Tumor (GIST)
What is being tested?
MEK162 and Pexidartinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
15 Apr 2017to 28 Apr 2021
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

  • Patients must have pathologically confirmed GIST.
  • In the Phase I dose escalation study, must have locally advanced, unresectable or metastatic GIST and have progressed on imatinib.
  • In the dose expansion portion of the phase I study, patients must have locally advanced, unresectable or metastatic GIST that is resistant to imatinib. This population includes patients who have not been treated with imatinib (imatinib-naïve) but considered to have primary resistance to imatinib, i.e. KIT/PDGFRA wild-type GIST, and patients with imatinib-refractory disease, i.e. has had prior treatment with imatinib.
  • Patients must be at least 18 years of age.
  • Disease must be measurable by RECIST 1.1.
  • ECOG Performance Status 0 or 1.
Show all 18Show fewer
  • Patient must be able to take oral medications.
  • Patients must sign an informed consent document.
  • Adequate renal, hepatic, and hematologic function defined by:
  • Serum Creatinine ≤ 1.5 mg/dL
  • Total Serum Bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • Serum AST (SGOT) and/or ALT (SGPT) ≤ 2.5 x ULN (or ≤ 5.0 x ULN if considered due to tumor)
  • ANC ≥ 1500/mm^3
  • Platelets ≥ 100,000/mm^3
  • Hemoglobin ≥ 9g/dL
  • Patients of childbearing potential are permitted in the study so long as they consent to avoid getting their partner pregnant or becoming pregnant, respectively, by using a reliable methods of contraception during and for 3 months following the last dose of the study drugs.
  • Females of childbearing potential must have a negative serum pregnancy test within 14 days of treatment.
  • Women of non-childbearing potential may be included if they are either surgically sterile or considered postmenopausal. Women who have documentation of at least 12 months of spontaneous amenorrhea and have an FSH level >40mIU/mL will be considered postmenopausal.

Who cannot join

  • Patients have a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
  • Patients have known active brain metastasis.
  • Leptomeningeal disease
  • Patients have known chronic liver disease (i.e., cirrhosis)
  • Active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus or known active or chronic infection with human immunodeficiency virus. Prior hepatitis infection that has been treated with highly effective therapy with no evidence of residual infection (including undetectable viral loads while on antiviral therapy) and with normal liver function (ALT, AST, total and direct bilirubin </= ULN) is allowed
  • Known active tuberculosis
Show all 24Show fewer
  • Concurrent active inoperable locally advanced or metastatic malignancy (other than malignancies, which the investigator determines are unlikely to interfere with treatment and safety analysis or are less of a treatment priority than their diagnosis of advanced GIST).
  • Patients have a history or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO) or predisposing factors to CSR or RVO (i.e. uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, hyperviscosity or hypercoagulability syndromes).
  • History of retinal degenerative disease.
  • History of Gilbert's syndrome.
  • Patients have clinically significant cardiovascular disease, including any of the following: 1) History of acute coronary syndrome including myocardial infarction, unstable angina, CABG, coronary angioplasty or stenting < 6 months prior to screening; 2) symptomatic chronic heart failure (New York Heart Association Criteria, Class II-IV); 3) evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities < 6 months prior to screening except atrial fibrillation (AF) and paroxysmal supraventricular tachycardia (PSVT).
  • A screening Fridericia corrected QT interval (QTcF) ≥ 450 ms (men) or ≥ 470 ms (women).
  • Left ventricular ejection fraction (LVEF) <50% as determined by a multigated acquisition (MUGA) scan or echocardiogram
  • Uncontrolled arterial hypertension defined as persistent elevation of systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100mmHg despite current therapy.
  • History of thromboembolic or cerebrovascular events ≤ 6 months prior to starting study treatment, including transient ischemic attacks, cerebrovascular accidents, deep vein thrombosis or pulmonary emboli
  • Patients who have neuromuscular disorders that are associated with elevated creatinine phosphokinase (i.e. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
  • Patients who are planning on embarking on a new strenuous exercise regimen after first dose of study treatment. NB: Muscular activities, such as strenuous exercise, that can result in significant increases in plasma CK levels should be avoided while on MEK162 treatment;
  • Impairment of gastrointestinal function or gastrointestinal disease (e.g., uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, ulcerative diseases, bowel resection with decreased intestinal absorption).
  • History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulatory or immunosuppressive medications or surgery) ≤ 12 months prior to randomization
  • Known history of acute or chronic pancreatitis
  • Patients had a major surgery within 3 weeks prior to study entry or who have not recovered from side effects of such procedure
  • Women who are pregnant or lactating.
  • Sexually active males unless they use a condom during intercourse while taking the drug and for 3 months after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.
  • Patients with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase I Study of Binimetinib in Combination With Pexidartinib in Patients With Advanced Gastrointestinal Stromal Tumor (GIST)

The purpose of this study is to test the safety and tolerability of the combination of pexidartinib and MEK162. This study tests different doses of pexidartinib in combination with different doses of MEK162 to see which dose combination of these drugs is safe and best tolerated in people.

Being tested
MEK162, Pexidartinib
Keywords
MEK162 (Binimetinib), Pexidartinib, 17-056
Medical subject headings
Gastrointestinal Stromal Tumors

What participants receive

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

  • MEK162Drug

    Also called Binimetinib

    MEK162 at 30mg twice daily

  • PexidartinibDrug

    pexidartinib 600mg daily (400mg in the morning, 200mg at night) for 4 weeks (1 cycle)

Study groups in NCT03158103
Study groupRoleWhat they receive
MEK162 in combination with PexidartinibExperimentalPexidartinib will be administered orally by the patients on a twice daily basis throughout the treatment cycle. Pexidartinib is available in 200mg tablets. MEK162 wiIl be administered orally on a twice daily basis throughout the treatment cycle. MEK162 is available in 15mg tablets. In this phase I study all patients will have a 2-week lead in of pexidartinib therapy alone. Thereafter, pexidartinib will be administered in combination with MEK162 on a consecutive daily basis. A treatment cycle consists of 28 days. In the dose escalation portion the dose of pexidartinib and MEK 162 will depend on the dose level cohort onto which the patient is enrolled.
Receives: Drug: MEK162; Drug: Pexidartinib

What is being measured

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

  1. Recommended phase II dose (RP2D)

    The dose escalation study will be pursued in standard 3+3 format, based on toxicities encountered during the first cycle of therapy.

    Measured: 1 year

Secondary outcomes (2)

  1. Number of participants with complete response

    defined by RECIST 1.1 criteria

    Measured: within 32 weeks

  2. Number of participants with partial response

    defined by RECIST 1.1 criteria

    Measured: within 32 weeks

Timeline

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

  1. First posted17 May 2017
  2. Study start15 Apr 2017
  3. Primary completion28 Apr 2021
  4. Study completion28 Apr 2021

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
Model description
The phase I study consists of a dose-escalation cohort and a dose-expansion cohort.
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03158103
Sponsor's protocol ID
17-056
Status last verified
Apr 2021
First submitted
16 May 2017
Last updated
30 Apr 2021
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Rosenbaum E, Kelly C, D'Angelo SP, Dickson MA, Gounder M, Keohan ML, Movva S, Condy M, Adamson T, Mcfadyen CR, Antonescu CR, Hwang S, Singer S, Qin LX, Tap WD, Chi P. A Phase I Study of Binimetinib (MEK162) Combined with Pexidartinib (PLX3397) in Patients with Advanced Gastrointestinal Stromal Tumor. Oncologist. 2019 Oct;24(10):1309-e983. doi: 10.1634/theoncologist.2019-0418. Epub 2019 Jun 18.

    PubMed 31213500

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MEK162 and Pexidartinib in people with Gastrointestinal Stromal Tumor (GIST), run by Memorial Sloan Kettering Cancer Center 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 18 inclusion and 24 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 30 Apr 2021. 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 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?

Recommended phase II dose (RP2D) (time frame: 1 year). 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 NCT03158103, 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 30 Apr 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in