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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02767804




Registration number
NCT02767804
Ethics application status
Date submitted
30/04/2016
Date registered
10/05/2016
Date last updated
20/08/2024

Titles & IDs
Public title
eXalt3: Study Comparing X-396 (Ensartinib) to Crizotinib in ALK Positive Non-Small Cell Lung Cancer (NSCLC) Patients
Scientific title
Phase 3 Randomized Study Comparing X-396 (Ensartinib) to Crizotinib in Anaplastic Lymphoma Kinase (ALK) Positive Non-Small Cell Lung Cancer (NSCLC) Patients
Secondary ID [1] 0 0
X396-CLI-301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - X-396 (ensartinib)
Treatment: Drugs - crizotinib

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

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


Treatment: Drugs: X-396 (ensartinib)
oral ALK inhibitor

Treatment: Drugs: crizotinib
oral ALK inhibitor
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival (PFS)
Timepoint [1] 0 0
36 months
Secondary outcome [1] 0 0
Overall survival (OS)
Timepoint [1] 0 0
48 months
Secondary outcome [2] 0 0
CNS response rate
Timepoint [2] 0 0
36 months
Secondary outcome [3] 0 0
ORR based on independent radiology review
Timepoint [3] 0 0
36 months

Eligibility
Key inclusion 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/12/2025
Actual
Sample size
Target
Accrual to date
Final
290
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Border Medical Oncology Research Unit - Albury
Recruitment hospital [2] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [3] 0 0
Chris O Brien Lifehouse - Camperdown
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
- Camperdown
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
Oregon
Country [5] 0 0
Argentina
State/province [5] 0 0
Rosario
Country [6] 0 0
Belgium
State/province [6] 0 0
Yvoir
Country [7] 0 0
Brazil
State/province [7] 0 0
SP
Country [8] 0 0
Brazil
State/province [8] 0 0
Fortaleza
Country [9] 0 0
Brazil
State/province [9] 0 0
São Paulo
Country [10] 0 0
Canada
State/province [10] 0 0
Quebec
Country [11] 0 0
China
State/province [11] 0 0
Anhui
Country [12] 0 0
China
State/province [12] 0 0
Beijing
Country [13] 0 0
China
State/province [13] 0 0
Fujian
Country [14] 0 0
China
State/province [14] 0 0
Guangdong
Country [15] 0 0
China
State/province [15] 0 0
Hebei
Country [16] 0 0
China
State/province [16] 0 0
Hubei
Country [17] 0 0
China
State/province [17] 0 0
Hunan
Country [18] 0 0
China
State/province [18] 0 0
Jiangsu
Country [19] 0 0
China
State/province [19] 0 0
Jilin
Country [20] 0 0
China
State/province [20] 0 0
Liaoning
Country [21] 0 0
China
State/province [21] 0 0
Shandong
Country [22] 0 0
China
State/province [22] 0 0
Shanghai
Country [23] 0 0
China
State/province [23] 0 0
Zhejiang
Country [24] 0 0
China
State/province [24] 0 0
Hangzhou
Country [25] 0 0
Czechia
State/province [25] 0 0
Ostrava-Vitkovice
Country [26] 0 0
Czechia
State/province [26] 0 0
Usti nad Labem
Country [27] 0 0
France
State/province [27] 0 0
Lille
Country [28] 0 0
France
State/province [28] 0 0
Montpellier
Country [29] 0 0
France
State/province [29] 0 0
Rennes
Country [30] 0 0
France
State/province [30] 0 0
Vellefaux
Country [31] 0 0
Germany
State/province [31] 0 0
Berlin
Country [32] 0 0
Germany
State/province [32] 0 0
Grosshansdorf
Country [33] 0 0
Hong Kong
State/province [33] 0 0
Hong Kong
Country [34] 0 0
Hong Kong
State/province [34] 0 0
Sha Tin
Country [35] 0 0
Israel
State/province [35] 0 0
Jerusalem
Country [36] 0 0
Israel
State/province [36] 0 0
Petah Tiqva
Country [37] 0 0
Italy
State/province [37] 0 0
Milano
Country [38] 0 0
Italy
State/province [38] 0 0
Perugia
Country [39] 0 0
Italy
State/province [39] 0 0
Sondrio
Country [40] 0 0
Korea, Republic of
State/province [40] 0 0
Seoul
Country [41] 0 0
Netherlands
State/province [41] 0 0
Amsterdam
Country [42] 0 0
Netherlands
State/province [42] 0 0
Maastricht
Country [43] 0 0
Poland
State/province [43] 0 0
Gdansk
Country [44] 0 0
Russian Federation
State/province [44] 0 0
Moscow
Country [45] 0 0
Russian Federation
State/province [45] 0 0
Omsk
Country [46] 0 0
Russian Federation
State/province [46] 0 0
Saint Petersburg
Country [47] 0 0
Spain
State/province [47] 0 0
Barcelona
Country [48] 0 0
Spain
State/province [48] 0 0
Palma de Mallorca
Country [49] 0 0
Turkey
State/province [49] 0 0
Edirne
Country [50] 0 0
United Kingdom
State/province [50] 0 0
Blackwood
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Bristol
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Nottingham
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Wirral

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Xcovery Holdings, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT02767804
Trial related presentations / publications
Horn L, Wang Z, Wu G, Poddubskaya E, Mok T, Reck M, Wakelee H, Chiappori AA, Lee DH, Breder V, Orlov S, Cicin I, Cheng Y, Liu Y, Fan Y, Whisenant JG, Zhou Y, Oertel V, Harrow K, Liang C, Mao L, Selvaggi G, Wu YL. Ensartinib vs Crizotinib for Patients With Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Randomized Clinical Trial. JAMA Oncol. 2021 Nov 1;7(11):1617-1625. doi: 10.1001/jamaoncol.2021.3523.
Public notes

Contacts
Principal investigator
Name 0 0
Giovanni Selvaggi, MD
Address 0 0
CEO
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02767804