Treating Patients With Melanoma and ALK Alterations With Ensartinib

Study 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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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: - Progression 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). Patients with uveal melanoma are exempt from PD-1 based progression since there is no accepted standard frontline therapy.
  • - 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. ° If a patient has consented to the pre-screening portion, has been determined to have ALK alterations, but has no measurable disease, the trial may be favored later, and the patient should be consented (or re-consented) to the treatment portion of the trial at the discretion of the investigator.
  • - 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 0-2 - 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) - Estimated glomerular filtration rate (GFR) ≥ 30 mL/min using a cancer-specific GFR Model; the calculator found at: http://tavarelab.
cruk.cam.ac.uk/JanowitzWilliamsGFR/
  • - 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 except for 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.
  • - 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03420508
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Memorial Sloan Kettering Cancer Center
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Alexander Shoushtari
Principal Investigator Affiliation Memorial Sloan Kettering Cancer Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Melanoma
Study Website: View Trial Website
Arms & Interventions

Arms

Experimental: ensartinib

The 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.

Interventions

Drug: - Ensartinib

Ensartinib will be given at a dose of 225mg daily in the form of 100mg and 25mg capsules. Patients will receive treatment continuously in 28 day cycles. Patients will then have the same tumor specimen biopsied again at day 15. Treatment will continue until disease progression, unacceptable toxicity, or patient choice to discontinue therapy.

Diagnostic Test: - ALKATI by Customized Nanostring Assay

a custom chip with probes targeting the ATI site in ALK, providing a reproducible, quantitative measure of ALKATI

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Memoral Sloan Kettering Monmouth, Middletown, New Jersey

Status

Recruiting

Address

Memoral Sloan Kettering Monmouth

Middletown, New Jersey, 07748

Site Contact

Alexander Shoushtari, MD

shoushta@mskcc.org

646-888-4161

Memorial Sloan Kettering Bergen, Montvale, New Jersey

Status

Recruiting

Address

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645

Site Contact

Alexander Shoushtari, MD

shoushta@mskcc.org

646-888-4161

Memorial Sloan Kettering Westchester, Harrison, New York

Status

Recruiting

Address

Memorial Sloan Kettering Westchester

Harrison, New York, 10604

Site Contact

Alexander Shoushtari, MD

shoushta@mskcc.org

646-888-4161

Memorial Sloan Kettering Cancer Center, New York, New York

Status

Recruiting

Address

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Site Contact

Alexander Shoushtari, MD

shoushta@mskcc.org

646-888-4161

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