Clinical trial NCT03155009: A Study of the Efficacy and Safety of Alectinib in Participants With Anaplastic Lymphoma Kinase (ALK)-Rearranged Non-Small Cell Lung Cancer
Official title: An Open-Label, Multicenter, Single-Arm, Phase II Study to Assess the Efficacy and Safety of Alectinib in Patients With ALK-Rearranged Non-Small Cell Lung Cancer After Disease Progression on Prior ALK Inhibitor Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-05-16
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy and safety of alectinib, in selected participants, with anaplastic lymphoma kinase-rearranged (ALK-rearranged) non-small cell lung cancer (NSCLC), after disease progression on prior treatment strategy with crizotinib, as only ALK inhibitor, and eventually chemotherapy treatment(s).


Eligibility criteria: Inclusion Criteria:

* Participants with histologically or cytologically confirmed locally advanced or metastatic NSCLC (Stage IIIB or IV accordingly to American Joint Committee on Cancer \[AJCC\] classification)
* Life expectancy of at least 12 weeks, in the opinion of the Investigator
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 2
* Having contributive biopsy performed on fresh tissue (FFPE blocks required) taken after progression on previous therapy showing presence of anaplastic lymphoma kinase (ALK) rearrangement, assessed by immunohistochemistry (IHC) and confirmed by fluorescence in situ hybridization (FISH)
* Absence of resistance mechanism to alectinib assessed by the Biomarkers Board
* Disease progression, limited to central nervous system (CNS) without possibility of tissue biopsy
* Non-contributive molecular analyses (not enough tumor cells or deoxyribonucleic acid, \[DNA\] amount or failure of analyses for technical reasons): inclusion is at investigator discretion (decision made upon Biomarker Board recommendation)
* History of crizotinib exposure
* Washout period: if previous progression on crizotinib: 7 days from last intake of the drug
* If previous progression on chemotherapy: 28 days
* If previous radiation therapy: 15 days
* Participants must have recovered from treatment toxicities to ≤ Grade 1 or to their pretreatment levels (for participants who have developed interstitial lung disease \[ILD\], they must have fully recovered)
* Recovery from effects of any major surgery, or significant traumatic injury, at least 35 days before the first dose of alectinib
* Adequate hematologic function
* Adequate renal function
* For all females of childbearing potential, a negative pregnancy test must be obtained within three days before starting study drug
* For women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use two adequate methods of contraception, including at least one method with a failure rate of \< 1% per year, during the treatment period and for at least 90 days after the last dose of study drug
* For men: agreement to remain abstinent or use a barrier method of contraception (e.g., condom) during the treatment period and for at least 90 days after the last dose of study drug and agreement to refrain from donating sperm during this same period
* Participant has national health insurance coverage

Exclusion Criteria:

* Prior therapy with other ALK inhibitors than crizotinib (including alectinib)
* Participants with symptomatic CNS metastases who are neurologically unstable or require increasing doses of steroids within one week prior to Day 0 to manage CNS symptoms
* Participants with progression limited to CNS and eligible to a focal treatment (surgery or stereotaxic radiotherapy)
* Administration of strong/ potent cytochrome P450 3A (CYP3A) inhibitors or inducers, or agents with potential QT prolonging effects within 14 days prior to first administration of study drug
* Liver disease
* 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 investigator, pose an unacceptable risk to the participant in this study
* Active or uncontrolled infectious diseases requiring treatment
* History of organ transplant
* Participants with baseline QTc \> 470 ms or participants with symptomatic bradycardia
* Pregnant or lactating women
* History of hypersensitivity to any of the additives in the alectinib drug
* Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the participant before trial entry
* Serious, uncontrolled infections or current known infection with human immunodeficiency virus (HIV).

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to 2 years
Secondary outcomes:
measure: Central Nervous System Objective Response Rate (C-ORR)
timeFrame: Up to 2 years
measure: Progression-Free Survival (PFS)
timeFrame: Up to 2 years
measure: Time to Progression (TTP)
timeFrame: Up to 2 years
measure: Disease Control Rate (DCR)
timeFrame: Up to 2 years
measure: Duration of Response (DOR)
timeFrame: Up to 2 years
measure: Central Nervous System DOR (C-DOR)
timeFrame: Up to 2 years
measure: Overall Survival (OS)
timeFrame: Up to 2 years
measure: Time to Central Nervous System (CNS) Progression
timeFrame: Up to 2 years
measure: Percentage of Participants with Adverse Events (AEs)
timeFrame: Up to 2 years
measure: Health-Related Quality of Life (QoL), as Assessed by the QLQ-C30 Questionnaire
timeFrame: Up to 2 years
measure: Health-Related QoL, as Assessed by the LC13 Questionnaire
timeFrame: Up to 2 years
measure: Health-Related QoL, as Assessed by the BN20 Questionnaire
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU Angers
city: Besancon
country: France
facility: Hopital Jean Minjoz; Pneumologie
city: Brest
country: France
facility: Hopital Augustin Morvan; Oncologie Thoracique
city: Caen
country: France
facility: Centre Francois Baclesse; Comite 3
city: Creteil
country: France
facility: Centre Hospitalier Intercommunal; Service de Pneumologie
city: La Tronche
country: France
facility: Hôpital Nord Michallon; Pneumologie
city: Lille
country: France
facility: CHRU Lille Service de Pneumologie et Oncologie Thoracique
city: Marseille
country: France
facility: Hôpital Nord - AP-HM Marseille#
city: Mulhouse
country: France
facility: Hopital Emile Muller;Pneumologie
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: Hopital Tenon;Pneumologie
city: Pessac
country: France
facility: CHU de Bordeaux
city: Rennes
country: France
facility: Hopital de Pontchaillou; Service de Pneumologie
city: Rouen
country: France
facility: CHU de Rouen - Hôpital Charles Nicolle
city: Toulouse cedex 9
country: France
facility: CHU de Toulouse - Hôpital Larrey; Service de pneumologie et oncologie pneumologique
city: Vantoux
country: France
facility: Hopital Robert Schuman; Pneumologie
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: