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

Sponsor
Xcovery Holding Company, LLC (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02767804
Collaborator
(none)
290
Enrollment
123
Locations
2
Arms
79
Anticipated Duration (Months)
2.4
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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 Design

Study Type:
Interventional
Actual Enrollment :
290 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jun 1, 2016
Actual Primary Completion Date :
Jun 30, 2020
Anticipated Study Completion Date :
Dec 31, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: X-396 (ensartinib)

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

Drug: X-396 (ensartinib)
oral ALK inhibitor
Active Comparator: crizotinib

Eligible patients with ALK+ NSCLC will receive oral crizotinib at 250mg BID with or without food until progression or unacceptable toxicity develops

Drug: crizotinib
oral ALK inhibitor
Other Names:
  • Xalkori

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progression-free survival (PFS) as assessed by independent radiology review based on RECIST v. 1.1 criteria [36 months]

    Secondary Outcome Measures

    1. Overall survival (OS) [48 months]

    2. CNS response rate based on independent radiology review [36 months]

    3. Time to CNS progression based on independent radiology review [36 months]

    4. ORR based on independent radiology review [36 months]

    Other Outcome Measures

    1. PFS based on investigator assessment [36 months]

    2. ORR based on investigator assessment [36 months]

    3. Time to response based on investigator assessment and independent radiology review [36 months]

    4. Duration of Response based on investigator assessment and independent radiology review [36 months]

    5. CNS response rate based on investigator assessment [36 months]

    6. Time to CNS progression based on investigator assessment [36 months]

    7. Patient reported time to deterioration (TTD) as measured by the EORTC C30/LC13 QoL questionnaire and Lung Cancer Symptom Scale (LCSS) [36 months]

    8. Patient reported health-related quality of life (HRQoL) as measured by the EORTC C30/LC13 QoL questionnaire and LCSS [36 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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:

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

    7. Platelets ≥100 x 109/L

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

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

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

    11. 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.

    12. 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.

    13. 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.

    14. 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.

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

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

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

    18. 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

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

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

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

    11. Women who are pregnant or breastfeeding.

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

    13. Patients at risk for GI perforation.

    14. Clinically significant cardiovascular disease including:

    15. 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.

    16. 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.

    5. 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.

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

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

    8. 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.

    9. 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

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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic Phoenix Arizona United States 85054
    2 Moffitt Cancer Center Tampa Florida United States 33612
    3 University Cancer & Blood Center Athens Georgia United States 30607
    4 Kaiser Permanente Hawaii- Moanalua Medical Center Honolulu Hawaii United States 96819
    5 Saint Alphonsus Regional Medical Center Boise Idaho United States 83706
    6 Henry Ford Hospital Detroit Michigan United States 48202
    7 Washington University School of Medicine Saint Louis Missouri United States 63110
    8 North Shore Hematology-Oncology Associates, PC East Setauket New York United States 11733
    9 Providence Portland Medical Center Portland Oregon United States 97213
    10 Vanderbilt University Nashville Tennessee United States 37240
    11 Inova Schar Cancer Institute Fairfax Virginia United States 22031
    12 Providence Regional Cancer System Lacey Washington United States 98503
    13 University of Wisconsin Clinical Science Center Madison Wisconsin United States 53792
    14 CEMIC Buenos Aires Argentina
    15 Fundacion Favaloro Caba Argentina
    16 Centro de Investigacion Pergamino SA Pergamino Argentina
    17 Sanatorio Parque S.A. Rosario Argentina
    18 Border Medical Oncology Research Unit Albury New South Wales Australia 2640
    19 Chris O'Brien Lifehouse Camperdown New South Wales Australia
    20 Princess Alexandra Hospital Woolloongabba Queensland Australia
    21 Chris O Brien Lifehouse Camperdown Australia
    22 Princess Alexandra Hospital Woolloongabba Australia
    23 UZ Brussel Brussels Belgium 1090
    24 CHU UCL Namur Yvoir Belgium 5530
    25 Instituto do Câncer do Estado de São Paulo São Paulo SP Brazil 01246-000
    26 Hospital de Câncer de Barretos - Fundação Pio XII São Paulo SP Brazil 14784-400
    27 Hospital Haroldo Juaçaba - Instituto do Cancêr do Ceará Fortaleza Brazil 60351-010
    28 Núcleo de Oncologia da Bahia - NOB Salvador Brazil 40170-110
    29 Fundacao do ABC Faculdade de Medicina do ABC Santo André Brazil 09060-650
    30 Hospital Paulistano São Paulo Brazil 01321
    31 Cross Cancer Institute Edmonton Alberta Canada T6G 1Z2
    32 Infirmière recherche Clinique, IUCPQ Quebec City Quebec Canada G1V 4G5
    33 Anhui Provincial Hospital Hefei Anhui China 230001
    34 Beijing Chao Yang Hospital Beijing Beijing China 100020
    35 Peking Union Medical College Hospital Beijing Beijing China 100032
    36 Peking University Cancer Hospital Beijing Beijing China 100142
    37 Beijing Chest Hospital,Capital Medical University Beijing Beijing China 101149
    38 Fujian Provincial Cancer Hospital Fuzhou Fujian China 350014
    39 Guangdong General Hospital Guangzhou Guangdong China 510080
    40 Fourth Hospital of Hebei Medical University Shijiazhuang Hebei China 050011
    41 Union Hospital of Tongji Medical College of Huazhong Science and Techology University Wuhan Hubei China 420104
    42 Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology Wuhan Hubei China 430030
    43 Hubei Cancer Hospital Wuhan Hubei China 430079
    44 Hunan Cancer Hospital Changsha Hunan China 410006
    45 Nanjing General Hospital Nanjing Jiangsu China 210002
    46 The Second Affiliated Hospital of Nanchang University Nanchang Jiangxi China 330006
    47 The First Bethune Hospital of Jilin University Changchun Jilin China 130000
    48 Jilin Cancer Hospital Changchun Jilin China 130012
    49 The First Hospital of China Medical University Shenyang Liaoning China 110001
    50 The Affiliated Hospital of Qingdao University Qingdao Shandong China 266071
    51 Shanghai Chest Hospital Shanghai Shanghai China 200030
    52 West China Hospital, Sichuan University Chengdu Sichuan China 610041
    53 Tianjin Medical University General Hospital Mailing No.154 Anshan Avenue Heping District Tianjin Tianjin China 300052
    54 Zhejiang Cancer Hospital Hangzhou Zhejiang China 310022
    55 Beijing Cancer Hospital Beijing China 100142
    56 Peking University Cancer Hospital Beijing China 100142
    57 Beijing Cancer Hospital Beijing China
    58 The First Affiliated Hospital, Zhejiang University Hangzhou China
    59 Zhejiang Cancer Hospital Hangzhou China
    60 Vítkovická Nemocnice , a.s. Ostrava-Vitkovice Czechia 70384
    61 Nemocnice Na Pleši s.r.o. Plesice Czechia 26204
    62 Krajská zdravotní, a.s., Masarykova nemocnice Usti nad Labem Czechia 40113
    63 Hopital Morvan CHRU de Brest Brest France 29200
    64 Centre GF Leclerc Dijon France 21000
    65 CHRU Lille Lille France 59000
    66 ICM Val d'Aurelle Montpellier France 34298
    67 Hôpital Saint-Louis Paris France 75010
    68 CHU de Rennes Hôpital Pontchaillou Rennes France 35033
    69 Institut de Cancérologie de l'Ouest (ICO) Saint Herblain France 44805
    70 Nouvel Hospital Civil de Stasbourg Strasbourg France 67091
    71 Klinik m. S. Infektiologie & Pneumologie Berlin Germany 13353
    72 Vivantes Klinikum Neukölln Berlin Germany D-12351
    73 Lungen Clinic Grosshansdorf Grosshansdorf Germany 22927
    74 Klinik Löwenstein gGmbH Med. Klinik II Onkologie Lowenstein Germany 74245
    75 Praxis Hämatologie und Onkologie Stolberg Stolberg Germany D-52222
    76 Queen Elizabeth Hospital Hong Kong Hong Kong
    77 The University of Hong Kong, Queen Mary Hospital Hong Kong Hong Kong
    78 The University of Hong Kong/Queen Mary Hospital Hong Kong Hong Kong
    79 Prince of Wales Hospital Sha Tin Hong Kong
    80 Soroka Medical Centre Be'er Sheva' Israel 84101
    81 Rambam Health Care Campus/ Oncology Institute Haifa Israel 31096
    82 Hadassah Medical Center Jerusalem Israel 9112001
    83 Rabin Medical Center Institute of Oncology, Davidoff Center Petah Tiqva Israel 49100
    84 Chaim Sheba Medical Center Ramat Gan Israel 5262000
    85 Centro Riferimento Oncologico CRO Aviano Aviano Italy 33081
    86 Ospedale Mater Salutis Legnago Italy 37045
    87 IRCCS - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Meldola Italy 47014
    88 IEO Istituto Europeo di Oncologia Milano Italy 20141
    89 AOU Federico II, Oncologia Medica Napoli Italy 80131
    90 Centro Operativo Studi Clinici S.C.Oncologia Medica Perugia Italy 06132
    91 UOC Oncologia Medica Ravenna Italy 48121
    92 Istituto Clinico Humanitas IRCCS Rozzano Italy 20089
    93 Azienda Socio Sanitaria Territoriale (ASST) della Valtellina e dell'Alto Laria Sondrio Italy 20121
    94 Seoul National University Hospital Seoul Korea, Republic of 03080
    95 Asan Medical Center Seoul Korea, Republic of 05505
    96 VU Medical Center Amsterdam Netherlands 1007 MB
    97 Maastricht University Medical Centre (MUMC) Maastricht Netherlands 6229HX
    98 Clínica Ricardo Palma Lima Peru
    99 Medical University of Gdansk Gdańsk Poland
    100 Centrum Onkologii-Instytut im. M. Sklodowskiej Curie Warsaw Poland
    101 Federal State Budgetary Scientific Institution Russian Oncological Scientific Center named after N.N. Blokhin Moscow Russian Federation 115478
    102 LLC "Vitamed" Moscow Russian Federation 121309
    103 State Budgetary Institution of Healthcare of the city of Moscow "MOSCOW CITY ONCOLOGY HOSPITAL # 62" Moscow Russian Federation 143423
    104 BHI of Omsk region "Clinical Oncology Dispensary" Omsk Russian Federation
    105 Pavlov First Medical University Saint Petersburg Russian Federation 197022
    106 FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov" Saint Petersburg Russian Federation
    107 Clinica Universidad de Navarra Pamplona Navarra Spain 31008
    108 Hospital Universitario Infanta Cristina Badajoz Spain 06080
    109 Hospital del Mar Barcelona Spain 08003
    110 Hospital de la Santa Creu i Sant Pau Barcelona Spain 08025
    111 Hospital Universitario Quirón Dexeus Barcelona Spain 08028
    112 Hospital Vall d'Hebrón Barcelona Spain 08035
    113 Hospital Parc Tauli' Barcelona Spain 08208
    114 ICO Girona - Hospital Doctor Josep Trueta Girona Spain 17007
    115 Hospital General Universitario Gregorio Marañon Madrid Spain
    116 Hospital Son Ltatzer Palma de Mallorca Spain 07198
    117 Trakya University Balkan Oncology Hospital Edirne Turkey 22030
    118 Istanbul University Cerrahpasa Medical Faculty Istanbul Turkey 34098
    119 Ege University Medical Faculty Izmir Turkey 35100
    120 Blackpool Victoria Hospital Blackwood United Kingdom FY3 8NR
    121 Southmead Hospital Bristol United Kingdom BS10 5NB
    122 Kings Mill hospital Nottingham United Kingdom NG17 4JL
    123 The Clatterbridge Cancer Centre NHS Foundation Trust Wirral United Kingdom CH63 4JY

    Sponsors and Collaborators

    • Xcovery Holding Company, LLC

    Investigators

    • Study Chair: Giovanni Selvaggi, MD, CEO

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Xcovery Holding Company, LLC
    ClinicalTrials.gov Identifier:
    NCT02767804
    Other Study ID Numbers:
    • X396-CLI-301
    First Posted:
    May 10, 2016
    Last Update Posted:
    Jan 31, 2022
    Last Verified:
    Jan 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Xcovery Holding Company, LLC
    ALK-positive NSCLC
    Additional relevant MeSH terms:
    Lung Neoplasms
    Carcinoma, Non-Small-Cell Lung
    Crizotinib
    Ensartinib

    Study Results

    No Results Posted as of Jan 31, 2022