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Advanced Uveal MelanomaPhase 1/2NCT05677373

Testing the Safety and Effectiveness of Combining Two Drugs, PLX2853 and Trametinib in the Treatment of Advanced Uveal Melanoma

A Phase 1/2 study testing BRD4 Inhibitor PLX2853, Trametinib and Computed Tomography in people with Advanced Uveal Melanoma and Metastatic Uveal Melanoma, run by Alliance for Clinical Trials in Oncology.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase I/II trial tests the safety, side effects, and best dose of PLX2853 in combination with trametinib in treating patients with uveal (eye) melanoma that has spread to other places in the body (metastatic) or nearby tissues or lymph nodes (locally advanced), or that cannot be removed by surgery (unresectable). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
BRD4 Inhibitor PLX2853, Trametinib and Computed Tomography
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
13 Jan 2023to 31 Jul 2025
Phase
Phase 1/2
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 histologically documented advanced uveal melanoma. Pathology review and confirmation of diagnosis will occur at the site enrolling the patient on this study. Patients must have locally advanced unresectable or metastatic uveal melanoma (UM).
  • Patients must have at least one lesion which is measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. Measurable disease is not required in the phase I portion
  • Patients may be treatment-naïve or have received any number of prior systemic or liver-directed therapies for advanced UM. There are no maximum number of prior therapies received
  • There is no specified washout time for prior therapies however patients must have fully recovered from acute toxicities related to prior anti-cancer therapies including
  • Cytotoxic therapies, immunotherapy, small molecule targeted agents, cell therapy, liver-directed therapy, or radiation therapy
  • Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative pregnancy test done =< 7 days prior to registration is required
Show all 21Show fewer
  • Age >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
  • Absolute neutrophil count (ANC) >= 1000/mm^3
  • Hemoglobin >= 9g/dL (transfusions to achieve this level are allowed)
  • Platelet count >= 100,000/mm^3
  • Creatinine clearance >= 45 mL/minute (per Cockcroft-Gault equation)
  • Total bilirubin =<1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN)
  • Prothrombin time (PT)/international normalized ratio (INR) =< 1.5 x upper limit of normal (ULN)
  • No history of any medical condition such as uncontrolled infection (including hepatitis B [HepB], hepatitis C [HepC]), uncontrolled diabetes mellitus or cardiac disease which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
  • Patients who are human immunodeficiency virus (HIV)-infected on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible
  • Patients with a new or progressive brain metastases (active brain metastases) or leptomeningeal disease if the treating physician determines that immediate central nervous system (CNS) specific treatment is not required and is unlikely to be required during the first cycle of therapy are eligible
  • Patients with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification with a class 2B or better are eligible
  • Patients must be able to obtain confirmation of payment coverage (insurance or other) for trametinib * Trametinib will not be provided by the Alliance and must be obtained through commercial or other mechanisms independent of the clinical trial. Confirmation of payment coverage or medication access must be obtained by treating physician prior to registration

Who cannot join

  • Patients must not have received prior treatment with a BET or MEK inhibitor
  • No patients who cannot swallow oral formulations of the agent(s)
  • Chronic concomitant treatment with strong inhibitors of CYP3A4 is not allowed on this study. Patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study

About this study

Official title: Phase I/II Study of BET and MEK Inhibition in Advanced Uveal Melanoma

This phase I/II trial tests the safety, side effects, and best dose of PLX2853 in combination with trametinib in treating patients with uveal (eye) melanoma that has spread to other places in the body (metastatic) or nearby tissues or lymph nodes (locally advanced), or that cannot be removed by surgery (unresectable). PLX2853 works by targeting and inhibiting certain activities within cells that promote tumor growth. By inhibiting these activities, PLX2853 may help to stabilize or reduce the growth of tumor cells. Trametinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps stop the spread of tumor cells. Giving PLX2853 in combination with trametinib may help to shrink and stabilize tumor cells in patients with advanced uveal melanoma.

Read the detailed description

CO-PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose(s) (MTD(s)) and recommended phase II dose. (Phase I) II. To evaluate whether combination BRD4 inhibitor PLX2853 (PLX2853) and trametinib demonstrate clinical activity in advanced uveal melanoma (UM), as determined by a best response rate of 25% compared to a historical rate of 10%. (Phase II)

SECONDARY OBJECTIVES:

  1. To evaluate the overall response rate (ORR) associated with combination PLX2853 and trametinib.

II. To evaluate the progression-free survival (PFS) associated with combination PLX2853 and trametinib.

III. To evaluate the overall survival (OS) associated with combination PLX2853 and trametinib.

IV. To characterize the adverse event profile associated with combination PLX2853 and trametinib.

PHARMACOKINETICS SECONDARY OBJECTIVE:

  1. To evaluate the pharmacokinetic profile of combination PLX2853 and trametinib.

OUTLINE: This is a phase I dose-escalation study of PLX2853 and trametinib followed by a phase II study.

Patients receive PLX2853 orally (PO) in combination with trametinib PO throughout the study. Patients also undergo computed tomography (CT) or magnetic resonance imaging (MRI) with contrast and collection of blood at screening and on study.

Being tested
BRD4 Inhibitor PLX2853, Trametinib, Computed Tomography, Magnetic Resonance Imaging, Biospecimen collection
Medical subject headings
Uveal Melanoma

What participants receive

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

  • BRD4 Inhibitor PLX2853Drug

    Also called PLX 2853, PLX-2853, PLX2853

    Given PO

  • TrametinibDrug

    Also called 871700-17-3, GSK1120212, JTP-74057

    Given PO

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT scan, Computed Axial Tomography, CT Scan

    Undergo CT with contrast

  • Magnetic Resonance ImagingProcedure or surgery

    Also called MRI

    Undergo MRI with contrast

  • Biospecimen collectionProcedure or surgery

    Undergo collection of blood

  • Biospecimen collectionProcedure or surgery

    Correlative studies

Study groups in NCT05677373
Study groupRoleWhat they receive
Treatment (PLX2853, trametinib)ExperimentalPatients receive PLX2853 PO in combination with trametinib PO throughout the study. Patients also undergo collection of blood at screening and on study. Patients also undergo CT or MRI with contrast and collection of blood at screening and on study.
Receives: Drug: BRD4 Inhibitor PLX2853; Drug: Trametinib; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen collection

What is being measured

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

  1. Maximum tolerated dose (MTD) (Phase I)

    Measured: Up to 28 days (Cycle 1)

  2. Recommended Phase 2 Dose (RP2D) (Phase I)

    Will be found using a Keyboard design which will be the dose with an estimated dose-limiting toxicity (DLT) rate closest to 25% (the target DLT rate).

    Measured: Up to 28 days (Cycle 1)

Secondary outcomes (7)

  1. Overall response rate (ORR) (phase II)

    Defined as the number of patients that achieve a best response of PR or better divided by the total number of evaluable patients. Will be evaluated using a Simon two-stage mini-max design using a historical response rate of 10% based on some prior work in this disease population with chemotherapy and targeted therapy. A 95% confidence interval for this estimate will also be calculated based on properties of the binomial distribution.

    Measured: 2 years

  2. Median progression-free survival (PFS)

    The Kaplan-Meier (KM) method will be used to estimate the median PFS time. A 95% confidence interval for the median PFS time will also be calculated using KM methodology.

    Measured: At 1 year

  3. Progression free survival (PFS)

    Will be estimated using Kaplan-Meier method, and a 95% confidence interval will also be calculated using KM methodology.

    Measured: From registration until first evidence of progression (or death), assessed up to 2 years

  4. Median overall survival (OS)

    The Kaplan-Meier method will be used to estimate the median PFS time. A 95% confidence interval for the median PFS time will also be calculated using KM methodology.

    Measured: At 1 year

  5. Overall survival (OS)

    Will be estimated using Kaplan-Meier method, and a 95% confidence interval will also be calculated using KM methodology.

    Measured: From registration until death due to any cause, assessed up to 2 years

  6. Incidence of adverse events

    Adverse events will be recorded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 for each patient. Frequency tables and summary statistics will be used and with the appropriate methods of evaluating categorical and continuous data.

    Measured: Up to 2 years

  7. Systemic exposure to trametinib and PLX2853 - pharmacokinetics

    Systemic exposure to trametinib and PLX2853 will be assessed by determining trough plasma concentrations (Ctrough, Cmin), which is the concentration in a sample collected immediately prior to a next dose. Ctrough will be determined throughout the first two treatment cycles on day 1 and day 15. Ctrough of trametinib and PLX2853 will be summarized using descriptive statistics. Dose dependency of Ctrough in phase 1 will be investigated using exploratory statistics. Potential changes in systemic exposure to either trametinib and/or PLX2853 over time will be explored by investigating changes in Ctrough during the two cycles. In addition, will use population PK models combined with the Ctroughs to describe the full PK of trametinib and PLX2853.

    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 posted10 Jan 2023
  2. Study start13 Jan 2023 (estimated)
  3. Primary completion31 Jul 2025 (estimated)
  4. Study completion31 Jul 2025 (estimated)

Why it stopped: The drug company supporting this trial has withdrawn support, including the ability to provide study agent.

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 1/2
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
NCT05677373
Sponsor's protocol ID
A092106
Status last verified
Aug 2023
First submitted
9 Jan 2023
Last updated
18 Aug 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing BRD4 Inhibitor PLX2853, Trametinib and Computed Tomography in people with Advanced Uveal Melanoma and Metastatic Uveal Melanoma, run by Alliance for Clinical Trials in Oncology.

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 21 inclusion and 3 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 18 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

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 combined 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.

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?

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 (MTD) (Phase I) (time frame: Up to 28 days (Cycle 1)). The study lists 2 primary outcomes in all. 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 NCT05677373.

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 18 Aug 2023.

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