eXalt3: Study Comparing X-396 (Ensartinib) to Crizotinib in ALK Positive Non-Small Cell Lung Cancer (NSCLC) Patients

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Brief Title

eXalt3: Study Comparing X-396 (Ensartinib) to Crizotinib in ALK Positive Non-Small Cell Lung Cancer (NSCLC) Patients

Official Title

Phase 3 Randomized Study Comparing X-396 (Ensartinib) to Crizotinib in Anaplastic Lymphoma Kinase (ALK) Positive Non-Small Cell Lung Cancer (NSCLC) Patients

Brief Summary

      The primary purpose of this study is to evaluate the efficacy and safety of X-396
      (ensartinib) vs. crizotinib in patients with ALK-positive non-small cell lung cancer that
      have received up to 1 prior chemotherapy regimen and no prior ALK inhibitor.
    

Detailed Description

      To evaluate the efficacy and safety of X-396 (ensartinib) vs. crizotinib in patients with
      ALK-positive NSCLC that have received up to 1 prior chemotherapy regimen and no prior ALK
      tyrosine kinase inhibitor (TKI), to obtain additional pharmacokinetic (PK) data from sparse
      PK sampling, to compare the quality of life (QoL) in patients receiving X-396 vs. crizotinib,
      to evaluate the status of exploratory biomarkers and correlate with clinical outcome, and to
      obtain germline DNA samples for possible pharmacogenetic analysis in the event that outliers
      with respect to efficacy, tolerability/safety, or exposure are identified.
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Progression-free survival (PFS) as assessed by independent radiology review based on RECIST v. 1.1 criteria

Secondary Outcome

 Overall survival (OS)

Condition

Non-small Cell Lung Cancer

Intervention

X-396 (ensartinib)

Study Arms / Comparison Groups

 X-396 (ensartinib)
Description:  Eligible patients with ALK+ NSCLC will receive oral X-396 (ensartinib) at 225mg QD with or without food until progression or unacceptable toxicity develops

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

290

Start Date

June 2016

Completion Date

March 31, 2021

Primary Completion Date

March 31, 2021

Eligibility Criteria

        Inclusion Criteria

          1. Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage
             IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is
             ALK-positive by an FDA-approved assay performed centrally. Patients must be ALK
             positive by local test prior to submitting tissue to the central lab. Randomization
             will occur after ALK positive confirmation is received from the central lab. Patients
             may have received up to 1 prior chemotherapy regimen for metastatic disease, which may
             also include maintenance therapy. Note that patients that have received adjuvant or
             neoadjuvant chemotherapy and developed metastatic disease within 6 months from the end
             of that therapy would be considered to have received 1 prior regimen for metastatic
             disease.

          2. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to 2.
             (see Appendix A)

          3. Life expectancy of at least 12 weeks.

          4. Ability to swallow and retain oral medication.

          5. Adequate organ system function, defined as follows:

               1. Absolute neutrophil count (ANC) ≥1.5 x 109/L

               2. Platelets ≥100 x 109/L

               3. Hemoglobin ≥9 g/dL (≥90 g/L) Note that transfusions are allowed to meet the
                  required hemoglobin level

               4. Total bilirubin ≤1.5 times the upper limit of normal (ULN)

               5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x ULN if
                  no liver involvement or ≤5 x ULN with liver involvement.

               6. Creatinine < 1.5 x ULN. If >1.5 x ULN, patient may still be eligible if
                  calculated creatinine clearance >50 mL/min (0.83mL/s) as calculated by the
                  Cockcroft-Gault method.

          6. Brain metastases allowed if asymptomatic at study baseline. Patients with untreated
             brain metastases must not be on corticosteroids. If patients have neurological
             symptoms or signs due to CNS metastases, patients need to complete whole brain
             radiation or focal treatment at least 14 days before start of study treatment and be
             asymptomatic on stable or decreasing doses of corticosteroids at baseline.

          7. Men with partners of childbearing potential willing to use adequate contraceptive
             measures during the study and for 90 days after the last dose of study medication.

          8. Women who are not of child-bearing potential, and women of child-bearing potential who
             agree to use adequate contraceptive measures during the study and for 90 days after
             the last dose of study medication, and who have a negative serum or urine pregnancy
             test within 1 week prior to initial trial treatment.

          9. Patients must be >18 years-of-age.

         10. Patients must have measurable disease per RECIST v. 1.1.

         11. Willingness and ability to comply with the trial and follow-up procedures.

         12. Ability to understand the nature of this trial and give written informed consent.

        Note the following pertains to patients enrolled in France

        In France, a subject will be eligible for inclusion in this study only affiliated to the
        French Social Security system, and currently benefit from the corresponding rights and
        cover.

        Exclusion Criteria

          1. Patients that have previously received an ALK TKI or PD-1/PD-L1 therapy, and patients
             currently receiving cancer therapy (i.e., other targeted therapies, chemotherapy,
             radiation therapy, immunotherapy, biologic therapy, hormonal therapy, surgery and/or
             tumor embolization).

          2. Use of an investigational drug within 21 days prior to the first dose of study drug.
             Note that to be eligible, any drug-related toxicity should have recovered to Grade 1
             or less, with the exception of alopecia.

          3. Any chemotherapy within 4 weeks, or major surgery or radiotherapy within the last 14
             days.

          4. Patients with primary CNS tumors and leptomeningeal disease are ineligible.

          5. Patients with a previous malignancy within the past 3 years (other than curatively
             treated basal cell carcinoma of the skin, in situ carcinoma of the cervix, or any
             cancer that is considered to be cured and have no impact on PFS and OS for the current
             NSCLC).

          6. Concomitant systemic use of anticancer herbal medications. These should be stopped
             prior to study entry.

          7. Patients receiving

               1. strong CYP3A inhibitors (including, but not limited to, atazanavir,
                  clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir,
                  ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, grapefruit,
                  grapefruit juice)

               2. strong CYP3A inducers (including, but not limited to, carbamazepine,
                  phenobarbital, phenytoin, rifabutin, rifampin, St. John's Wort)

               3. CYP3A substrates with narrow therapeutic window (including, but not limited to,
                  alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide,
                  quinidine, sirolimus, tacrolimus).

          8. Women who are pregnant or breastfeeding.

          9. Presence of active gastrointestinal (GI) disease or other condition that will
             interfere significantly with the absorption, distribution, metabolism, or excretion of
             study medications.

         10. Patients at risk for GI perforation.

         11. Clinically significant cardiovascular disease including:

               1. QTcF interval >450 ms for men and >470 ms for women, symptomatic bradycardia <45
                  beats per minute or other significant ECG abnormalities in the investigator's
                  opinion.

               2. Clinically uncontrolled hypertension in the investigator's opinion (e.g., blood
                  pressure >160/100 mmHg; note that isolated elevated readings considered to not be
                  indicative of uncontrolled hypertension are allowed).

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

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

               2. Arrhythmia or conduction abnormality requiring medication. Note: patients with
                  atrial fibrillation/flutter controlled by medication and arrhythmias controlled
                  by pacemakers are eligible.

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

               4. Cerebrovascular accident or transient ischemia.

         12. Patients who are immunosuppressed (including known HIV infection), have a serious
             active infection at the time of treatment, have interstitial lung disease/pneumonitis,
             or have any serious underlying medical condition that would impair the ability of the
             patient to receive protocol treatment. Patients with controlled hepatitis C, in the
             investigator's opinion, are allowed. Patients with known hepatitis B must be HBeAg and
             HB viral DNA negative for enrollment. Note that, because of the high prevalence, all
             patients in the Asia-Pacific region (except Australia, New Zealand, and Japan) must be
             tested and, if HBsAg positive, must be HBeAg and HB viral DNA negative for enrollment.

         13. Known hypersensitivity to tartrazine, a dye used in the ensartinib 100 mg capsule.

         14. Psychological, familial, sociological, or geographical conditions that do not permit
             compliance with the protocol.

         15. Concurrent condition that in the investigator's opinion would jeopardize compliance
             with the protocol or would impart excessive risk associated with study participation
             that would make it inappropriate for the patient to be enrolled.

         16. Inability or unwillingness to comply with study and/or follow-up procedures outlined
             in the protocol.

             Note the following pertains to patients enrolled in France

         17. In France, a subject will not be eligible when under legal protection.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, , 

Location Countries

Argentina

Location Countries

Argentina

Administrative Informations


NCT ID

NCT02767804

Organization ID

X396-CLI-301


Responsible Party

Sponsor

Study Sponsor

Xcovery Holding Company, LLC


Study Sponsor

, , 


Verification Date

August 2020