Clinical Trials /

Study of Trametinib + Ceritinib in Patients With Unresectable Melanoma

NCT03501368

Description:

The main purpose of this study is to determine the risks and benefits of ceritinib (ZYKADIA) given in combination with trametinib (MEKINIST) in patients who have progressed on prior melanoma therapy.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Trametinib + Ceritinib in Patients With Unresectable Melanoma
  • Official Title: Phase 1 Study of Trametinib + Ceritinib in Patients With Unresectable Melanoma

Clinical Trial IDs

  • ORG STUDY ID: MCC-19475
  • NCT ID: NCT03501368

Conditions

  • Melanoma
  • Unresectable Melanoma
  • Advanced Melanoma

Interventions

DrugSynonymsArms
CeritinibZYKADIATrametinib + Ceritinib Treatment
TrametinibMEKINISTTrametinib + Ceritinib Treatment

Purpose

The main purpose of this study is to determine the risks and benefits of ceritinib (ZYKADIA) given in combination with trametinib (MEKINIST) in patients who have progressed on prior melanoma therapy.

Detailed Description

      Ceritinib that has been approved for patients with metastatic non-small cell lung cancer
      (NSCLC) by the US Food and Drug Administration (FDA). While ceritinib is not currently
      FDA-approved specifically in melanoma, researchers believe ceritinib may also help keep
      melanoma cancer cells from growing and therefore potentially help patients with melanoma as
      well. Trametinib is currently FDA-approved for melanoma with a BRAFV600-mutation.
    

Trial Arms

NameTypeDescriptionInterventions
Trametinib + Ceritinib TreatmentExperimentalStudy treatment will be given in cycles. Each cycle will be 4 weeks (28 days). Post-Treatment (follow-up) Period: Participants will return to the study site between 30-40 days after the last dose of trametinib + ceritinib for an end-of-treatment assessment. Additional follow-up will occur for related Adverse Events (AEs) that are not resolved by this time and related Serious Adverse Events (SAEs) that occur after the time of this visit. Participants will be followed for survival every 3 months for the first year following end of treatment, and then every 6 months for up to 5 years after end of treatment.
  • Ceritinib
  • Trametinib

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of advanced/unresectable melanoma (AJCC v.8 Stage 3C/D/4)

          -  Measurable disease, defined as per Response Evaluation Criteria in Solid Tumors
             (RECIST) 1.1

          -  Must have at least one tumor site accessible for a biopsy

          -  Documented disease refractory to at least one PD1/PD-L1 (+/- CTLA-4) inhibitor
             treatment, or intolerance to these drugs and if BRAFV600-mutant melanoma, refractory
             disease to at least one BRAF and MEK inhibitor (defined as progression while on
             treatment), or intolerance to these drugs

          -  Last line of treatment prior to study enrollment must not have been BRAF/MEK inhibitor
             therapy

          -  Prior treatment-related toxicity resolved to ≤ Grade 2 or baseline

          -  Prior radiation allowed

          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤2

          -  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 for 90 days after completion of trametinib +
             ceritinib administration.

          -  Participants must have normal organ and marrow function.

        Exclusion Criteria:

          -  Potential participants with known hypersensitivity to any of the excipients of
             trametinib, ceritinib (microcrystalline cellulose, mannitol, crospovidone, colloidal
             silicon dioxide and magnesium stearate).

          -  An untreated or uncontrolled brain metastases or evidence of leptomeningeal disease.
             Patients with asymptomatic brain metastases or previously treated brain metastases
             that are stable (i.e., not requiring corticosteroids) at the time of study start will
             be eligible.

          -  Previous malignancy is not an exclusion provided that the other malignancy is
             considered under control, patient is not on concomitant anti-cancer drug therapy, and
             target lesions from melanoma are clearly defined for response assessment.

          -  Other severe, acute, or chronic medical conditions including uncontrolled diabetes
             mellitus or psychiatric conditions or laboratory abnormalities that, in the opinion of
             the investigator, may increase the risk associated with study participation or may
             interfere with the interpretation of study results.

          -  Clinically significant, uncontrolled heart disease and/or recent cardiac event (within
             6 months), such as:

               1. unstable angina within 6 months prior to screening;

               2. myocardial infarction within 6 months prior to screening;

               3. history of documented congestive heart failure (New York Heart Association
                  functional classification III-IV);

               4. cardiac arrhythmias not controlled with medication;

               5. Corrected QT (QTcF) >470 ms at baseline

          -  A history of interstitial lung disease or interstitial pneumonitis, including
             clinically significant radiation pneumonitis (i.e., affecting activities of daily
             living or requiring therapeutic intervention). (Note, this does NOT include
             immune-mediated pneumonitis)

          -  Impaired gastrointestinal (GI) function or GI disease that may alter absorption of
             study drugs or inability to swallow

          -  Receiving medications that meet one of the following criteria and that cannot be
             discontinued at least 1 week prior to start of treatment with study drugs and for the
             duration of participation:

               1. Medication with a known risk of prolonging the QT interval or inducing Torsades
                  de Pointes

               2. Strong inhibitors or strong inducers of CYP3A4/5, and Medications with a low
                  therapeutic index that are primarily metabolized by CYP3A4/5, and/or CYP2C9

               3. Therapeutic doses of warfarin sodium (Coumadin) or any other coumadin-derived
                  anti-coagulant. Anticoagulants not derived from warfarin are allowed (e.g.,
                  dabigatran, rivaroxaban, apixaban).

               4. Unstable or increasing doses of corticosteroids in the 5 days before first dose
                  of study treatment.

               5. Enzyme-inducing anticonvulsive agents
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum Tolerated Dose (MTD) and recommended Phase 2 Dose (RP2D)
Time Frame:Up to 12 months
Safety Issue:
Description:Maximum Tolerated Dose and recommended phase 2 dose of trametinib + ceritinib, determined by number and frequency of treatment related adverse events

Secondary Outcome Measures

Measure:Median Progression-free Survival (PFS)
Time Frame:Up to 5 years post treatment
Safety Issue:
Description:PFS is defined from the time of on-treatment to time of progression, censoring at last clinical follow up or if no longer followed at Moffitt, then based on date of last medical documentation of no progression. Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Measure:Overall Survival (OS)
Time Frame:Up to 5 years post treatment
Safety Issue:
Description:OS is defined as from the time of on-treatment to the time of death, censoring at last date known alive.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • cutaneous
  • refractory
  • melanoma
  • ceritinib

Last Updated

November 3, 2020