Phase 3, Randomized Study Comparing Ensartinib to Crizotinib in Anaplastic Lymphoma Kinase (ALK) Positive Non-Small Cell Lung Cancer (NSCLC) Patients
- Conditions
- longkankerALK-positive Non-Small Cell Lung Cancer
- Registration Number
- NL-OMON54615
- Lead Sponsor
- Xcovery Holdings Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 10
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 mestatic disease , which may
also include maintenance therapy.
2. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0
to 2.
3. Life expectancy of at least 12 weeks.
4. Ability to swallow and retain oral medication.
5. Adequate organ system function, defined as follows:
a. Absolute neutrophil count (ANC) >=1.5 x 109/L
b. Platelets >=100 x 109/L
c. Hemoglobin >=9 g/dL (>=90 g/L) Note that transfusions are allowed to
meet the required hemoglobin level.
d. Total bilirubin <=1.5 times the upper limit of normal (ULN)
e. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=2.5 x
ULN if no liver involvement or <=5 x ULN with liver involvement.
f. Creatinine <=1.5 x ULN. If >1.5 x ULN, patient may still be eligible if
calculated creatinine clearance >=50 mL/min (0.83 mL/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 childbearing
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. Patients must be ALK-positive by IHC. Testing will be done centrally;
however, patients will be allowed to enroll based on local results (positive by
FISH or IHC), if available.
12. Willingness and ability to comply with the trial and follow-up procedures.
13. Ability to understand the nature of this trial and give written informed
consent.
1. Patients that have previously received an ALK TKI or PD-1 or 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 systematic use of anti-cancer herbal medications. These should
be stopped prior to study entry.
7.Patients receiving
a. strong CYP3A inhibitors (including, but not limited to, atazanavir,
clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone,
nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin,
voriconazole, grapefruit, grapefruit juice)
b. strong CYP3A inducers (including, but not limited to, carbamazepine,
phenobarbital, phenytoin, rifabutin, rifampin, St. John's Wort)
c. 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:
a. QTcF interval >450 ms for men and >470 ms for woman, symptomatic bradycardia
<45 beats per minute or other significant ECG abnormalities in the
investigator's opinion.
b. 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:
a. Congestive heart failure (New York Heart Class III or IV).
b. Arrhythmia or conduction abnormality requiring medication. Note: patients
with atrial fibrillation/flutter controlled by medication and arrhythmias
controlled by pacemakers are eligible.
c. Severe/unstable angina, coronary artery/peripheral bypass graft, or
myocardial infarction.
d. 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 pre
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Progression-free survival (PFS) as assessed by independent radiology review<br /><br>based on RECIST v. 1.1 criteria.</p><br>
- Secondary Outcome Measures
Name Time Method <p>• Key Secondary Efficacy Endpoints: Overall survival, CNS response rate (based<br /><br>on IRR), time to CNS progression (based on IRR), objective response rate (based<br /><br>on IRR)<br /><br>• Other Secondary Efficacy Endpoints: PFS (based on investigator assessment),<br /><br>ORR (based on investigator assessment), time to response (based on investigator<br /><br>assessment and IRR), duration of response (based on investigator assessment and<br /><br>IRR), CNS response rate (based on investigator assessment ), time to CNS<br /><br>progression (based on investigator assessment)..<br /><br><br /><br>Exploratory:<br /><br>Patient reported time to deterioration (TTD) as measured by the EORTC C30/LC13<br /><br>QoL questionnaire and Lung Cancer Symptom Scale (LCSS), patient reported<br /><br>healthrelated quality of life (HRQoL) as measured by the EORTC C30/LC13 QoL<br /><br>questionnaire and LCSS, pharmacodynamic (PD) and possible pharmacogenetic (PG)<br /><br>assessments.</p><br>