Alectinib versus crizotinib in previously untreated patients with ALK-positive non-small cell lung cancer.
- Conditions
- Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC)MedDRA version: 21.1Level: PTClassification code 10029521Term: Non-small cell lung cancer stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 21.1Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-004133-33-PT
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Recruiting
- Sex
- All
- Target Recruitment
- 303
•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 as assessed by the Ventana IHC test. Sufficient tumor tissue to perform ALK IHC and ALK FISH is required. Both tests will be performed at designated central laboratories.
•Measurable disease (by RECIST v1.1) prior to the administration of study treatment.
•Patients had no prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC.
•ECOG PS of 0-2.
•Adequate hematologic, renal and liver function.
•Patients must have recovered from effects of any major surgery orsignificant traumatic injury at least 28 days before the first dose of study
treatment.
•Prior brain or leptomeningeal metastases allowed if asymptomatic (e.g., diagnosed incidentally at study baseline). Asymptomatic CNS
lesions might be treated at the discretion of the investigator as per local clinical practice. If patients have neurological symptoms or signs due to
CNS metastasis, patients need to complete whole brain radiation or gamma knife irradiation treatment. In all cases, radiation treatment
must be completed at least 14 days before enrollment and patients must be clinically stable.
•Able and willing to provide written informed consent prior to performing any study related procedures and to comply with the study protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 211
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 92
•Patients with a previous malignancy within the past 3 years are excluded (other than curatively treated basal cell carcinoma of the skin,
early gastrointestinal (GI) cancer by endoscopic resection, in situ carcinoma of the cervix, or any cured cancer that is considered to have
no impact in PFS and OS for the current NSCLC).
•Any gastrointestinal (GI) disorder that may affect absorption of oral medications, such as mal-absorption syndrome or status post-major bowel resection.
•National Cancer Institute Common Terminology Criteria for Adverse
Events (version 4.0) Grade 3 or higher toxicities due to any prior therapy
such as radiotherapy (excluding alopecia), which have not shown
improvement and are strictly considered to interfere with current study
medication
•Co-administration of anti-cancer therapies other than those
administered in this study
•Liver disease characterized by:
ALT or AST > 3 × Upper Limit of Normal (ULN = 5 × ULN for patients with concurrent liver
metastasis) confirmed on two consecutive measurements
OR
Impaired excretory function (e.g., hyperbilirubinemia) or synthetic function or other conditions of decompensated liver disease such as
coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices
OR
Acute viral or active autoimmune, alcoholic, or other types of acute hepatitis
•Patients with baseline QTc > 470 milliseconds (ms) or symptomatic bradycardia
•Administration of strong/potent cytochrome P4503A inhibitors or inducers within 14 days prior to the first dose of study treatment and while on treatment with alectinib or crizotinib except for oral corticosteroids up to 20 mg of prednisolone equivalent per day.
•Administration of agents with potential QT interval prolonging effects within 14 days prior to the first administration of study for all patients drug and while on treatment through the end of the study for crizotinib-treated patients only.
•History of organ transplant
•Pregnant or lactating women
•Known HIV positivity or AIDS-related illness.
•History of hypersensitivity to any of the additives in the alectinib drug formulation (lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, hydroxypropyl cellulose, sodium lauryl sulfate [SLS], magnesium stearate).
•History of hypersensitivity to any of the additives in the crizotinib drug formulation (silica, colloidal anhydrous cellulose, microcrystalline calcium hydrogen phosphate, anhydrous sodium starch glycolate, magnesium stearate).
•Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or the absorption of oral medications or that would, in the opinion of the Principal Investigator, pose an unacceptable risk to the patient in this study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Investigator assessed progression-free survival (PFS);Secondary Objective: PFS by the independent review committee (IRC); time to CNS progression by IRC; Objective Response Rate (ORR) and Duration of Response (DOR); time to deterioration (TTD) in patient-reported lung cancer symptoms; health-related quality of life (HRQoL); safety and tolerability; pharmacokinetics of alectinib and metabolite(s); overall survival (OS).;Primary end point(s): •PFS<br>;Timepoint(s) of evaluation of this end point: The time from date of randomization to the date of first documented disease progression (as per RECIST 1.1) or death, whichever occurs first
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1 PFS by IRC<br>2 Time to CNS Progression<br>3 ORR<br>4 DOR<br>5 Time to deterioration (TTD) in patient-reported lung cancer symptoms<br>6 Health-related quality of life (HRQoL)<br>7 Safety and tolerability<br>8 Pharmacokinetics of alectinib and metabolite(s)<br>9 Overall survival (OS);Timepoint(s) of evaluation of this end point: 1 The same methodology as specified for PFS<br>2 The time from randomization until radiographic evidence of CNS progression<br>3 The percentage of patients who attain a CR or PR (as per RECIST 1.1) <br>4. The time from when response (CR or PR) was first documented to first documented disease progression or death (whichever occurs first)<br>5-6 From baseline until disease progression and during post-progression on treatment in case of isolated, asymptomatic CNS progression; and at survival follow-up for 6 months<br>7 Throughout the study<br>8 Until disease progression<br>9 The time from the date of randomization to the date of death due to any cause