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Comparison of Standard Dose Alectinib to Alectinib in Adjusted Dose Based on Alectinib Bloodlevels (ADAPT ALEC)

Primary Purpose

Drug Monitoring, Carcinoma, Non-Small-Cell Lung, Lung Cancer

Status
Recruiting
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Alectinib
Sponsored by
University Medical Center Groningen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Drug Monitoring focused on measuring Alectinib, Randomized Controlled Trial

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with locally advanced or metastatic NSCLC (stage IIIB to stage IV by AJCC 8th)
  • ECOG performance status 0-4
  • Histologically or cytology confirmed NSCLC
  • Documented ALK rearrangement based on an EMA approved test
  • Patients can either be chemotherapy-naïve or have received one line of platinum-based chemotherapy
  • 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
  • Measurable disease (by RECIST criteria version 1.1) prior to the first dose of study treatment
  • Signed writte Institutional Review Board (IRB)/Ethical Committee (EC) approved informed consent form, prior to performing any study-related procedures
  • Observational other studies are allwoed for patients included in this study
  • Local radiotherapy is allowed for pain

Exclusion Criteria:

  • Any significant concomitant disease determined by the investigator to be potentially aggravated by the investigational drug
  • 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)
  • 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.
  • 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 patient before trial entry.

Sites / Locations

  • Gustave Roussy
  • Radboud University Medical Center
  • Maastricht University Medical Center +Recruiting
  • The Netherlands Cancer InstituteRecruiting
  • Amsterdam University Medical CenterRecruiting
  • Leiden University Medical CenterRecruiting
  • Erasmus Medical CenterRecruiting
  • University Medical Center GroningenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

TDM-guided dosing arm

Standard dose arm

Arm Description

Alectinib plasmaconcentration will be blinded untill the end of the trial. No intervention based on the alectinib plasmaconcentrion will be performed. In case of unacceptable toxicity (i.e. unbearable or persistent grade 2 toxicity and grade 3/4 toxicity), the alectinib dose can be reduced by 150mg BID.

Outcomes

Primary Outcome Measures

Median progression free survival (mPFS)
PFS is measured from start of treatment to progressive disease, death or lost to follow-up.Patients who did not die or progress, or lost to follow-up, will be censored at their last available date.

Secondary Outcome Measures

Succesfull Therapeutic Drug monitoring
The percentage of succesfull TDM interventions, in which successful is defines as tartget attainment and manageable toxicity.
Overall response rate (ORR)
ORR is the percentage of patients with partial response or complete response, according to RECIST v1.1, of the total treated population.
Median overall survival
mOS is defined as time from randomization to death from any cause in the total population.
Intracranial PFS
PFS is measured from start of treatment to progressive disease in the brain, death or lost to follow-up. Patients who did not die or progress, or lost to follow-up, will be censored at their last available date.
Patient adherence to alectinib treatment
This will be estimated by pill counts of returned medication as well as a patient diary on drug intake.
Number of adverse events (AE) related to plasma concentration and dose increases
AE's will be defined using CTCAE v5.0. Number of AE's in the subgroups of patients with Cmin <435 ng/mL compared to Cmin >= 435 ng/ML, and in patients who did and who did not receive a TDM-guided dose increase.
European Organization for Research and Treatment of Cancer 30-item core quality of life questionnaire (EORTC QLQ-C30) and the the Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC-13) module
Mean change from baseline in EORTC QLQ-C30 and QLQ-LC13 scores
European Quality of Life Five Dimensions with five levels (EQ-5D-5L) questionnaire
Mean change from baseline in EQ-5D-5L score
Incremental cost-effectiveness ratio (ICER)
The ICER is the final outcome of the comparative cost-effectiveness analysis performed using a health-state transition model to compare costs and effectiveness between both study arms.
Alectinib M4 protein
Alectinib M4 plasmaconcentrations in relation to alectinib plasma concentrations

Full Information

First Posted
August 26, 2022
Last Updated
February 20, 2023
Sponsor
University Medical Center Groningen
Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Erasmus Medical Center, Maastricht University Medical Center, Radboud University Medical Center, The Netherlands Cancer Institute, Leiden University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT05525338
Brief Title
Comparison of Standard Dose Alectinib to Alectinib in Adjusted Dose Based on Alectinib Bloodlevels
Acronym
ADAPT ALEC
Official Title
Standard Dosed Alectinib Versus Therapeutic Drug Monitoring Guided Alectinib Dosing
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 23, 2022 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Medical Center Groningen
Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Erasmus Medical Center, Maastricht University Medical Center, Radboud University Medical Center, The Netherlands Cancer Institute, Leiden University Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The ADAPT ALEC randomized controlled trial (RCT) is performed in patients with Anaplastic Lymphoma Kinase (ALK) positive non-small cell lung cancer (NSCLC). The RCT will compare the use of Therapeutic Drug Monitoring (TDM) and dose increases if alectinib 35 ng/Ml (arm A) with standard of care (arm B).
Detailed Description
The ADAPT ALEC trial is a phase IV, RCT in patients with ALK positive NSCLC treated with alectinib. A longer median progression free survival (mPFS) is expected in patients treated with standard dose alectinib when minimum plasma concentrations (Cmin) of alectinib exceed 435 ng/mL. The ADAPT ALEC trial will investigate whether using therapeutic drug monitoring (TDM) and increasing the dose of alectinib in patients with Cmin <435 ng/mL, will raise the mPFS. We will compare mPFS in the subgroup of patients with an alectinib Cmin <435 ng/mL using TDM and dose increases (arm A) to fixed dosing/standard of care (arm B).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Drug Monitoring, Carcinoma, Non-Small-Cell Lung, Lung Cancer, Anaplastic Lymphoma Kinase Gene Mutation, Anaplastic Lymphoma Kinase Gene Translocation
Keywords
Alectinib, Randomized Controlled Trial

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Both study-arms will receive oral alectinib (Alecensa®, Roche). In arm A (TDM arm), the alectinib dose will be increased if Cmin <435 ng/mL and manageable toxicity. In both arms, alectinib dose can be reduced based on toxicity.
Masking
None (Open Label)
Masking Description
The alectinib Cmin for patients treated in arm B (standard dose arm) will be blinded to participants and care providers
Allocation
Randomized
Enrollment
196 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TDM-guided dosing arm
Arm Type
Experimental
Arm Title
Standard dose arm
Arm Type
No Intervention
Arm Description
Alectinib plasmaconcentration will be blinded untill the end of the trial. No intervention based on the alectinib plasmaconcentrion will be performed. In case of unacceptable toxicity (i.e. unbearable or persistent grade 2 toxicity and grade 3/4 toxicity), the alectinib dose can be reduced by 150mg BID.
Intervention Type
Drug
Intervention Name(s)
Alectinib
Intervention Description
In case of an alectinib plasmaconcentration Cmin <435 ng/mL, determined by TDM, and manageable toxicity, the alectinib dose will be increased with 150mg BID up to a maximum of 900mg BID. In case of unacceptable toxicity (i.e. unbearable or persistent grade 2 toxicity and grade 3/4 toxicity), the alectinib dose can be reduced by 150mg BID.
Primary Outcome Measure Information:
Title
Median progression free survival (mPFS)
Description
PFS is measured from start of treatment to progressive disease, death or lost to follow-up.Patients who did not die or progress, or lost to follow-up, will be censored at their last available date.
Time Frame
mPFS will be assessed through study completion, after 12 months of follow-up.
Secondary Outcome Measure Information:
Title
Succesfull Therapeutic Drug monitoring
Description
The percentage of succesfull TDM interventions, in which successful is defines as tartget attainment and manageable toxicity.
Time Frame
4 to 6 weeks after dose adjustment based on TDM
Title
Overall response rate (ORR)
Description
ORR is the percentage of patients with partial response or complete response, according to RECIST v1.1, of the total treated population.
Time Frame
Response will be assessed every 2-3 months. ORR will be determined after total study completion and 12 months of follow-up
Title
Median overall survival
Description
mOS is defined as time from randomization to death from any cause in the total population.
Time Frame
Through total study completion, after 12 months of follow-up
Title
Intracranial PFS
Description
PFS is measured from start of treatment to progressive disease in the brain, death or lost to follow-up. Patients who did not die or progress, or lost to follow-up, will be censored at their last available date.
Time Frame
Progressive disease will be assessed once every 2-3 months. Intracranial PFS will be assessed through total study completion, after 12 months of follow-up
Title
Patient adherence to alectinib treatment
Description
This will be estimated by pill counts of returned medication as well as a patient diary on drug intake.
Time Frame
Through study completion, an average of 2 years
Title
Number of adverse events (AE) related to plasma concentration and dose increases
Description
AE's will be defined using CTCAE v5.0. Number of AE's in the subgroups of patients with Cmin <435 ng/mL compared to Cmin >= 435 ng/ML, and in patients who did and who did not receive a TDM-guided dose increase.
Time Frame
Through total study completion, after 12 months of follow-up
Title
European Organization for Research and Treatment of Cancer 30-item core quality of life questionnaire (EORTC QLQ-C30) and the the Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC-13) module
Description
Mean change from baseline in EORTC QLQ-C30 and QLQ-LC13 scores
Time Frame
Questionnaires will be filled in at baseline and every 3 months thereafter through study completion, an average of 2 years.
Title
European Quality of Life Five Dimensions with five levels (EQ-5D-5L) questionnaire
Description
Mean change from baseline in EQ-5D-5L score
Time Frame
Questionnaire will be filled in at baseline and every 3 months thereafter through study completion, an average of 2 years.
Title
Incremental cost-effectiveness ratio (ICER)
Description
The ICER is the final outcome of the comparative cost-effectiveness analysis performed using a health-state transition model to compare costs and effectiveness between both study arms.
Time Frame
Through total study completion, after 12 months of follow-up
Title
Alectinib M4 protein
Description
Alectinib M4 plasmaconcentrations in relation to alectinib plasma concentrations
Time Frame
Through total study completion, after 12 months of follow-up

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with locally advanced or metastatic NSCLC (stage IIIB to stage IV by AJCC 8th) ECOG performance status 0-4 Histologically or cytology confirmed NSCLC Documented ALK rearrangement based on an EMA approved test Patients can either be chemotherapy-naïve or have received one line of platinum-based chemotherapy 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 Measurable disease (by RECIST criteria version 1.1) prior to the first dose of study treatment Signed writte Institutional Review Board (IRB)/Ethical Committee (EC) approved informed consent form, prior to performing any study-related procedures Observational other studies are allwoed for patients included in this study Local radiotherapy is allowed for pain Exclusion Criteria: Any significant concomitant disease determined by the investigator to be potentially aggravated by the investigational drug 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) 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. 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 patient before trial entry.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
M.B. Muntinghe-Wagenaar, Msc
Phone
+31503616161
Email
adaptalec@umcg.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
A.J. van der Wekken, PhD
Organizational Affiliation
University Medical Center Groningen
Official's Role
Principal Investigator
Facility Information:
Facility Name
Gustave Roussy
City
Villejuif
State/Province
Val-de-Marne
ZIP/Postal Code
94805
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
B. Besse, PhD
Facility Name
Radboud University Medical Center
City
Nijmegen
State/Province
Gelderland
ZIP/Postal Code
6525 GA
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
M.M. van den Heuvel, PhD
Facility Name
Maastricht University Medical Center +
City
Maastricht
State/Province
Limburg
ZIP/Postal Code
6229 HX
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
L.E.L. Hendriks, PhD
Facility Name
The Netherlands Cancer Institute
City
Amsterdam
State/Province
Noord-Holland
ZIP/Postal Code
1066 CX
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
A.J. de Langen, PhD
Facility Name
Amsterdam University Medical Center
City
Amsterdam
State/Province
Noord-Holland
ZIP/Postal Code
1105 AZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
S.M.S. Hashemi, Msc
Facility Name
Leiden University Medical Center
City
Leiden
State/Province
Zuid-Holland
ZIP/Postal Code
2333 ZA
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
E.F. Smit, PhD
Facility Name
Erasmus Medical Center
City
Rotterdam
State/Province
Zuid-Holland
ZIP/Postal Code
3015 GD
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
A.C. Dingemans, PhD
Facility Name
University Medical Center Groningen
City
Groningen
ZIP/Postal Code
9713GZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
A.J. van der Wekken, PhD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data that underlie the results will only be shared upon reasonable request from the Principal Investigator at the UMCG, who will discuss the request with the ADAPT ALEC study team.
IPD Sharing Time Frame
The study protocol will be available after ending of the study and publication of the manuscript ending 5 years after article publication.
IPD Sharing Access Criteria
For individual participant data meta-analysis

Learn more about this trial

Comparison of Standard Dose Alectinib to Alectinib in Adjusted Dose Based on Alectinib Bloodlevels

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