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A Study of the Efficacy and Safety of Alectinib in Participants With Anaplastic Lymphoma Kinase (ALK)-Rearranged Non-Small Cell Lung Cancer (ATALK)

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ClinicalTrials.gov Identifier: NCT03155009
Recruitment Status : Recruiting
First Posted : May 16, 2017
Last Update Posted : June 15, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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).

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: Alectinib Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 73 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 10, 2017
Estimated Primary Completion Date : July 19, 2019
Estimated Study Completion Date : May 28, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Alectinib

Arm Intervention/treatment
Experimental: Alectinib
600 mg orally twice daily (BID) for up to 2 years
Drug: Alectinib
600 mg orally BID with food




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Up to 2 years ]
    ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) assessed by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST), v.1.1. CR is defined as disappearance of all target and non-target lesions and no new lesions, and all pathological lymph nodes must have decreased to <10 mm in short axis. PR is defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions.


Secondary Outcome Measures :
  1. Central Nervous System Objective Response Rate (C-ORR) [ Time Frame: Up to 2 years ]
    C-ORR is defined as the percentage of participants who attain a CR or PR of the baseline CNS metastases based on RECIST v.1.1. CR is defined as disappearance of all target and non-target lesions and no new lesions, and all pathological lymph nodes must have decreased to <10 mm in short axis. PR is defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions.

  2. Progression-Free Survival (PFS) [ Time Frame: Up to 2 years ]
    PFS is defined as the time between first intake of alectinib and the first occurrence of disease progression, or death from any cause during the study, whichever occurs first. Progressive disease (PD) based on RECIST v.1.1. is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

  3. Time to Progression (TTP) [ Time Frame: Up to 2 years ]
    TTP is defined as the time between first intake of alectinib and the first occurrence of disease progression. PD based on RECIST v.1.1. is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

  4. Disease Control Rate (DCR) [ Time Frame: Up to 2 years ]
    DCR is defined as the percentage of participants who attain CR, PR, or stable disease (SD) for at least five weeks, based on RECIST v.1.1. CR is defined as disappearance of all target and non-target lesions and no new lesions, and all pathological lymph nodes must have decreased to <10 mm in short axis. PR is defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum on study.

  5. Duration of Response (DOR) [ Time Frame: Up to 2 years ]
    DOR is defined as the time from when response (CR or PR), based on RECIST v.1.1, will be first documented to first documented disease progression or death (whichever occurs first). CR is defined as disappearance of all target and non-target lesions and no new lesions, and all pathological lymph nodes must have decreased to <10 mm in short axis. PR is defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

  6. Central Nervous System DOR (C-DOR) [ Time Frame: Up to 2 years ]
    C-DOR is defined as the time from the first observation of a CNS response of CR or PR based on RECIST V1.1 until first observation of CNS progression or death from any cause (whichever occurs first). CR is defined as disappearance of all target and non-target lesions and no new lesions, and all pathological lymph nodes must have decreased to <10 mm in short axis. PR is defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

  7. Overall Survival (OS) [ Time Frame: Up to 2 years ]
    OS is defined as the percentage of participants alive two years after the start of treatment.

  8. Time to Central Nervous System (CNS) Progression [ Time Frame: Up to 2 years ]
    Time to central nervous system (CNS) progression is defined as the time from first drug intake to first documented occurrence of disease progression in the CNS. PD based on RECIST v.1.1. is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

  9. Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 2 years ]
    An adverse event is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsen during the study are reported as adverse events.

  10. Health-Related Quality of Life (QoL), as Assessed by the QLQ-C30 Questionnaire [ Time Frame: Up to 2 years ]
    The QLQ-C30 Questionnaire is used to assess the quality of life of participants with cancer. It includes five functional scales, three symptom scales, a global health status / QoL scale, and six single items. These components range in score from 0 (low response level) to 100 (high response level).

  11. Health-Related QoL, as Assessed by the LC13 Questionnaire [ Time Frame: Up to 2 years ]
    The LC13 Questionnaire includes 13 questions assessing lung cancer-associated symptoms (cough, hemoptysis, dyspnea and site-specific pain), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy and alopecia), and pain medication. This scale ranges in score from 0 (low response level) to 100 (high response level).

  12. Health-Related QoL, as Assessed by the BN20 Questionnaire [ Time Frame: Up to 2 years ]
    The BN20 Questionnaire includes 20 items assessing future uncertainty, visual disorder, motor dysfunction, communication deficit and other disease symptoms, and treatment toxicities. This scale ranges in score from 0 (low response level) to 100 (high response level).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03155009


Contacts
Contact: Reference Study ID Number: ML39349 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S.Only) global-roche-genentech-trials@gene.com

Locations
France
CHU Angers Recruiting
Angers, France, 49933
Hopital Jean Minjoz; Pneumologie Recruiting
Besancon, France, 25030
Hôpital Ambroise Paré - Boulogne-Billancourt Recruiting
Boulogne Billancourt, France, 92100
Hopital Augustin Morvan; Oncologie Thoracique Recruiting
Brest, France, 29609
Hopital Louis Pradel; Pneumologie Recruiting
Bron, France, 69677
Centre Francois Baclesse; Comite 3 Recruiting
Caen, France, 14076
Centre Hospitalier Intercommunal; Service de Pneumologie Active, not recruiting
Creteil, France, 94010
Hôpital Nord Michallon; Pneumologie Recruiting
La Tronche, France, 38700
CHRU Lille Service de Pneumologie et Oncologie Thoracique Active, not recruiting
Lille, France, 59000
Hôpital Universitaire Dupuytren Withdrawn
Limoges, France, 87042
Hôpital Nord - AP-HM Marseille# Active, not recruiting
Marseille, France, 13915
Hôpital Arnaud de Villeneuve Recruiting
Montpellier, France, 34295
Hopital Emile Muller;Pneumologie Recruiting
Mulhouse, France, 68070
Institut Curie Recruiting
Paris, France, 75005
Hopital Tenon;Pneumologie Active, not recruiting
Paris, France, 75970
CHU de Bordeaux Recruiting
Pessac, France, 33600
Hopital de Pontchaillou; Service de Pneumologie Active, not recruiting
Rennes, France, 35033
CHU de Rouen - Hôpital Charles Nicolle Recruiting
Rouen, France, 76031
Hopital Civil; Pneumology Recruiting
Strasbourg, France, 67091
Hopital Sainte Musse; Pneumologie Recruiting
Toulon, France, 83056
CHU de Toulouse - Hôpital Larrey; Service de pneumologie et oncologie pneumologique Active, not recruiting
Toulouse Cedex 9, France, 31059
Hopital Robert Schuman; Pneumologie Recruiting
Vantoux, France, 57070
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03155009     History of Changes
Other Study ID Numbers: ML39349
2016-003924-22 ( EudraCT Number )
First Posted: May 16, 2017    Key Record Dates
Last Update Posted: June 15, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases