alectinib for ALK-positive non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- Patients with locally advanced or metastatic NSCLC (stage IIIB to stage IV by AJCC 8th)\n- Observational other studies are allowed for patients included in this study\n- Local radiotherapy is allowed for pain\n- Male or female >=18 years old\n- ECOG Performance Status of 0-4\n- Histologically or cytology confirmed NSCLC\n- Documented ALK rearrangement based on an EMA approved test\n- Patients can either be chemotherapy-naïve or have received one line of platinum-based chemotherapy\n- Patients with brain or leptomeningeal metastases are allowed on the study if the lesions are asymptomatic without neurological signs and clinically stable for at least 2 weeks without steroid treatment. Patients who do not meet these criteria are not eligible for the study.\n- Measurable disease (by RECIST criteria version 1.1) prior to the first dose of study treatment\n- Signed written Institutional Review Board (IRB)/Ethical Committee (EC) approved informed consent form, prior to performing any study-related procedures."}

Exclusion criteria

• {"criterion_text":"- Any significant concomitant disease determined by the investigator to be potentially aggravated by the investigational drug\n- Consumption of agents which modulate CYP3A4 or agents with potential QT prolonging effects within 14 days prior to admission and during the study (see concomitant medication restrictions)\n- 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 absorption of oral medications, or that would, in the opinion of the Principal Investigator, pose an unacceptable risk to the subject in this study.\n- 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 patiënt before trial entry."}

Primary endpoints

• {"endpoint_text":"- The main endpoint will be an increase in progression free survival (PFS according to RECIST v1.1) in the subgroups of patients with an alectinib Cmin treshhold <435 ng/mL in the TDM-guided dosing cohort versus the same subgroup in the fixed dosing cohort","definition_or_measurement_approach":"PFS measured according to RECIST v1.1 in the subgroup of patients with an alectinib Cmin threshold <435 ng/mL comparing TDM-guided dosing cohort versus fixed dosing cohort."}

Secondary endpoints

• {"endpoint_text":"- Feasibility and safety of TDM. This will be measured as percentage of successful TDM measures, in which successful is defined as target attainment with manageable toxicity.","definition_or_measurement_approach":"Measured as percentage of successful TDM measures; success defined as target attainment with manageable toxicity."}
• {"endpoint_text":"- Physician adherence to TDM advice. This will be measured as the percentage of dose recommendations that are implemented by the treating physicians.","definition_or_measurement_approach":"Measured as percentage of dose recommendations implemented by treating physicians."}
• {"endpoint_text":"- Overall response rates (ORR). ORR will be defined as partial response or complete response (according to RECIST v1.1) percentage of the total treated population.","definition_or_measurement_approach":"ORR defined as percentage with partial response or complete response per RECIST v1.1 in total treated population."}
• {"endpoint_text":"- Median overall survival (mOS). OS will be defined as the time from randomization to death from any cause in the total population. Patients who do not die or are lost to follow-up will be censored at their last available date.","definition_or_measurement_approach":"OS defined as time from randomization to death from any cause; censoring at last available date for patients not dead or lost to follow-up."}
• {"endpoint_text":"- Intracranial PFS. The intracranial PFS will be measured as time from start of treatment to progressive disease in the brain, or death from any cause. Patients who did not die or progress, or lost to follow-up, will be censored at their last available date.","definition_or_measurement_approach":"Time from start of treatment to progressive disease in the brain or death; censoring at last available date for those without event."}
• {"endpoint_text":"- Patient adherence. This will be estimated by pill counts of returned medication as well as a patient diary on drug intake.","definition_or_measurement_approach":"Estimated by pill counts of returned medication and patient diary on drug intake."}
• {"endpoint_text":"- Toxicity related to the plasma concentration and dose increases. This will be defined as AE’s in the subgroups with Cmin < 435 ng/mL and all Cmin ≥ 435 ng/mL, and in patients who did and who did not receive a PK-guided dose increase.","definition_or_measurement_approach":"Defined as adverse events in subgroups by Cmin (<435 ng/mL vs ≥435 ng/mL) and by receipt of PK-guided dose increase."}
• {"endpoint_text":"- Quality of life (QoL). This will be determined using the EORTC QLQ_LC13 as addition to the QLQ-C30 questionnaire, and the EQ-5D-5L questionnaire.","definition_or_measurement_approach":"QoL measured using EORTC QLQ-LC13 in addition to QLQ-C30, and EQ-5D-5L questionnaires."}
• {"endpoint_text":"- Cost-effectiveness. This will be determined by the incremental cost-effectiveness ratio based on costs and quality adjusted life-years (QALYs)","definition_or_measurement_approach":"Determined by incremental cost-effectiveness ratio based on costs and QALYs."}
• {"endpoint_text":"- Alectinib-M4 concentrations. These will be measured in the alectinib plasma samples.","definition_or_measurement_approach":"Measured in alectinib plasma samples."}

Netherlands

Earliest CTIS Part Ii Submission Date

18-12-2023

Latest Decision Or Authorization Date

27-03-2025

Processing Time Days

465

Number Of Sites

8

Number Of Participants

186

France

Earliest CTIS Part Ii Submission Date

27-06-2024

Latest Decision Or Authorization Date

02-04-2025

Processing Time Days

279

Number Of Sites

1

Number Of Participants

10

Primary sponsor

Full Name

Universitair Medisch Centrum Groningen

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands