Clinical Trials /

Treating Patients With Melanoma and ALK Alterations With Ensartinib

NCT03420508

Description:

The purpose of this study is to test the effects of the study drug, ensartinib, on the patient and the cancer. Ensartinib is a new, investigational type of treatment for melanoma with a particular type of abnormality.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Treating Patients With Melanoma and ALK Alterations With Ensartinib
  • Official Title: A Phase 2 Study of the ALK Inhibitor Ensartinib for Patients With Melanomas Harboring ALK Alterations or Aberrant ALK Expression

Clinical Trial IDs

  • ORG STUDY ID: 17-471
  • NCT ID: NCT03420508

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
Ensartinibensartinib

Purpose

The purpose of this study is to test the effects of the study drug, ensartinib, on the patient and the cancer. Ensartinib is a new, investigational type of treatment for melanoma with a particular type of abnormality.

Trial Arms

NameTypeDescriptionInterventions
ensartinibExperimentalThe screening portion of the trial will test archival tumor material for the presence of ALKATI using a Nanostring-based RNA assay for any patients deemed to be current or future candidates for this trial. This will require approximately 5 formalin-fixed paraffin- embedded (FFPE) slides of 5-8 micron thickness. For the treatment portion of the study, all patients will receive ensartinib orally at a dose of 225mg daily.
  • Ensartinib

Eligibility Criteria

        Inclusion Criteria:

        For Screening Phase:

          -  Patients ≥18 years of age

          -  Histologically confirmed advanced malignant melanoma, regardless of subtype

        For Treatment Phase, as above and in addition:

          -  progressing following PD-1 based checkpoint inhibitor therapy, with or without
             ipilimumab. Tumors harboring BRAF V600 alterations must also have received prior
             therapy with BRAF inhibitors (with or without a MEK inhibitor).

          -  Tumors must harbor an alteration in ALK using a CLIA-certified laboratory, including,
             but not limited to, ALKATI, ALK fusions, or ALK mutations.

          -  Disease must be measurable according to RECIST 1.1. Disease that has undergone local
             therapy in the past 30 days is not considered measurable unless the investigator has
             documented progression despite the local therapy.

          -  Asymptomatic untreated brain metastases are allowed. Symptomatic metastases that have
             undergone local therapy with RT or surgery and have not required an increase in
             steroid dose in prior 2 weeks are allowed. Disease that has undergone local therapy is
             not considered measurable.

          -  Patients must have an Eastern Cooperative Oncology Group (ECOG) Performance Status
             (PS) of 0-1

          -  Acceptable liver, renal, and hematological function:

               -  total bilirubin ≤1.5x upper limit of normal (ULN); patients with Gilbert's
                  Syndrome must have bilirubin ≤3x ULN

               -  Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤3
                  x ULN (≤5x if liver metastases are present)

               -  Serum creatinine ≤1.5 x ULN

               -  Hemoglobin ≥9 g/dL

               -  Neutrophils ≥1.5 x 10^9/L

               -  Platelets ≥100 x 10^9/L

               -  Prothrombin time, international normalized ratio [INR], and/or activated partial
                  thromboplastin time within ≤1.5 x ULN

          -  Prothrombin time, international normalized ratio [INR], and/or activated partial
             thromboplastin time within ≤1.5 x ULN

        Exclusion Criteria:

        For Screening Phase:

          -  Any prior ALK inhibition.

        For Treatment Phase, as above and in addition:

        Prior therapy with immune-activating agents within less than 1 cycle length prior to first
        day of study treatment (e.g. 3 weeks for ipilimumab or pembrolizumab; 2 weeks for
        nivolumab).

          -  Prior therapy with BRAF/MEK agents within 3 weeks prior to first day of study
             treatment.

          -  Any other systemic or regional anticancer therapy (cytotoxic chemotherapy,
             embolization) within 3 weeks or 1 cycle length, whichever is shorter, prior to first
             day of study treatment

          -  Prior RT or clinically relevant major surgery (e.g. craniotomy, metastasectomy) within
             2 weeks prior to first day of study treatment.

          -  Any other active malignancy other than melanoma that, in the opinion of the
             investigator, would interfere with study participation.

          -  Receipt of any other systemic anticancer therapy with the exception of hormonal
             therapy for a hormonally sensitive (e.g. breast or prostate) cancer.

          -  Receipt of strong CYP3A inhibitors or inducers per Appendix A.

          -  Clinically significant cardiovascular disease, including:

               -  QTc interval by Bazett's formula >480 ms

               -  Symptomatic bradycardia <45 beats per minute

               -  Other clinically significant ECG abnormalities (e.g. bundle branch block) may be
                  eligible after discussion with the Principal Investigator

               -  Clinically uncontrolled hypertension in the investigator's opinion.

          -  The following within 6 months prior to Cycle 1 Day 1:

               -  Congestive heart failure (New York Heart Class III or IV).

               -  Cardiomyopathy.

               -  o Arrhythmia or conduction abnormality requiring medication. Note: patients with
                  atrial fibrillation/flutter adequately controlled by medication in the opinion of
                  the treating physician and arrhythmias controlled by pacemakers are eligible.

               -  Severe/unstable angina, coronary artery/peripheral bypass graft, or myocardial
                  infarction.

               -  Cerebrovascular accident or transient ischemia.

          -  Known HIV infection, solid organ transplantation, or other immunosuppressed state

          -  Any serious, active infection at the time of treatment such as bacteremia

          -  Interstitial lung disease or pneumonitis that is symptomatic or may interfere with the
             detection or management of suspected drug-related pulmonary toxicity. Patients with
             prior pneumonitis that has resolved are eligible.

          -  Patients must not be pregnant or breast feeding, or unable or unwilling to use proper
             contraception during the study and up to 3 months following study completion.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:clinical benefit rate (CBR)
Time Frame:up to 24 weeks
Safety Issue:
Description:CBR is defined as any confirmed objective response by Response Evaluation in Solid Tumor (RECIST) 1.1, or stable disease until the 24 week assessment.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Ensartinib
  • ALK Inhibitor
  • ALK Alterations
  • Aberrant ALK Expression
  • 17-471

Last Updated

January 29, 2018