Drug MonitoringPhase 4ADAPT ALECNCT05525338
Comparison of Standard Dose Alectinib to Alectinib in Adjusted Dose Based on Alectinib Bloodlevels
A Phase 4 study testing Alectinib in people with Drug Monitoring and Carcinoma, Non-Small-Cell Lung, run by University Medical Center Groningen at 8 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Drug Monitoring, Carcinoma, Non-Small-Cell Lung, Lung Cancer
- What is being tested?
- Alectinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 196 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 23 Mar 2022to 31 Dec 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- 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.
Trial locations and contacts
8 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
8 sites in 2 countries
Netherlands7 sites, 7 recruiting
- Recruiting
The Netherlands Cancer Institute
Amsterdam, North Holland, 1066 CX
A.J. de Langen, PhD
- Recruiting
Amsterdam University Medical Center
Amsterdam, North Holland, 1105 AZ
S.M.S. Hashemi, Msc
- Recruiting
University Medical Center Groningen
Groningen, 9713GZ
A.J. van der Wekken, PhD
- Recruiting
Leiden University Medical Center
Leiden, South Holland, 2333 ZA
E.F. Smit, PhD
- Recruiting
Maastricht University Medical Center +
Maastricht, Limburg, 6229 HX
L.E.L. Hendriks, PhD
- Recruiting
Radboud University Medical Center
Nijmegen, Gelderland, 6525 GA
M.M. van den Heuvel, PhD
- Recruiting
Erasmus Medical Center
Rotterdam, South Holland, 3015 GD
A.C. Dingemans, PhD
France1 site, 1 recruiting
- Not yet recruiting
Gustave Roussy
Villejuif, Val-de-Marne, 94805
B. Besse, PhD
About this study
Official title: Standard Dosed Alectinib Versus Therapeutic Drug Monitoring Guided Alectinib Dosing
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).
Read the 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).
- Conditions
- Drug Monitoring, Carcinoma, Non-Small-Cell Lung, Lung Cancer, Anaplastic Lymphoma Kinase Gene Mutation, Anaplastic Lymphoma Kinase Gene Translocation
- Being tested
- Alectinib
- Keywords
- Alectinib, Randomized Controlled Trial
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlectinibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| TDM-guided dosing arm | Experimental | Not described Receives: Drug: Alectinib |
| Standard dose arm | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: mPFS will be assessed through study completion, after 12 months of follow-up.
Secondary outcomes (10)
Succesfull Therapeutic Drug monitoring
The percentage of succesfull TDM interventions, in which successful is defines as tartget attainment and manageable toxicity.
Measured: 4 to 6 weeks after dose adjustment based on TDM
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.
Measured: Response will be assessed every 2-3 months. ORR will be determined after total study completion and 12 months of follow-up
Median overall survival
mOS is defined as time from randomization to death from any cause in the total population.
Measured: Through total study completion, after 12 months of follow-up
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.
Measured: 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
Patient adherence to alectinib treatment
This will be estimated by pill counts of returned medication as well as a patient diary on drug intake.
Measured: Through study completion, an average of 2 years
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.
Measured: Through total study completion, after 12 months of follow-up
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
Measured: Questionnaires will be filled in at baseline and every 3 months thereafter through study completion, an average of 2 years.
European Quality of Life Five Dimensions with five levels (EQ-5D-5L) questionnaire
Mean change from baseline in EQ-5D-5L score
Measured: Questionnaire will be filled in at baseline and every 3 months thereafter through study completion, an average of 2 years.
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.
Measured: Through total study completion, after 12 months of follow-up
Alectinib M4 protein
Alectinib M4 plasmaconcentrations in relation to alectinib plasma concentrations
Measured: Through total study completion, after 12 months of follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2022
- Study start23 Mar 2022
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Drug MonitoringStudies of the same condition, open and under way.
- More trials run by University Medical Center GroningenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 196 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Center Groningen
- Sponsor type
- University, hospital or other
- Collaborators
- Amsterdam University Medical Center, Erasmus Medical Center, Maastricht University Medical Center, Radboud University Medical Center, The Netherlands Cancer Institute, Leiden University Medical Center
- Responsible party
- Sponsor
- Investigators
- A.J. van der Wekken, PhD, Principal investigator, University Medical Center Groningen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05525338
- Sponsor's protocol ID
- 202000251
- Other IDs
- 2020-001737-13, NL9411
- Acronym
- ADAPT ALEC
- Status last verified
- May 2024
- First submitted
- 26 Aug 2022
- Last updated
- 13 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Meertens M, Muntinghe-Wagenaar MB, Sikkema BJ, Lopez-Yurda M, Retel VP, Paats MS, Ter Heine R, Schuuring E, Timens W, Touw DJ, van Boven JFM, de Langen AJ, Hashemi SMS, Hendriks LEL, Croes S, van den Heuvel MM, Dingemans AC, Mathijssen RHJ, Smit EF, Huitema ADR, Steeghs N, van der Wekken AJ. Therapeutic drug monitoring guided dosing versus standard dosing of alectinib in advanced ALK positive non-small cell lung cancer patients: Study protocol for an international, multicenter phase IV randomized controlled trial (ADAPT ALEC). Front Oncol. 2023 Mar 9;13:1136221. doi: 10.3389/fonc.2023.1136221. eCollection 2023.
PubMed 36969063
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Standard Dosed Alectinib Versus Therapeutic Drug Monitoring Guided Alectinib Dosing
- ClinicalTrials.gov ID
- NCT05525338
- Acronym / sponsor ID
- ADAPT ALEC / 202000251
- Conditions
- Drug Monitoring, Carcinoma, Non-Small-Cell Lung, Lung Cancer, Anaplastic Lymphoma Kinase Gene Mutation, Anaplastic Lymphoma Kinase Gene Translocation
- Keywords
- Alectinib, Randomized Controlled Trial
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 196 participants (estimated)
- Lead sponsor
- University Medical Center GroningenUniversity, hospital or other
- Collaborators
- Amsterdam University Medical Center, Erasmus Medical Center, Maastricht University Medical Center, Radboud University Medical Center, The Netherlands Cancer Institute, Leiden University Medical Center
- Study start
- 23 Mar 2022 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 1 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| TDM-guided dosing arm | Experimental | Drug: Alectinib |
| Standard dose arm | No intervention | –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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlectinibIn 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. | Drug | TDM-guided dosing arm |
Primary outcome
Median progression free survival (mPFS)
Time frame: mPFS will be assessed through study completion, after 12 months of follow-up.
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.
10 secondary outcomes
Succesfull Therapeutic Drug monitoring
Time frame: 4 to 6 weeks after dose adjustment based on TDM
Overall response rate (ORR)
Time frame: Response will be assessed every 2-3 months. ORR will be determined after total study completion and 12 months of follow-up
Median overall survival
Time frame: Through total study completion, after 12 months of follow-up
Intracranial PFS
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
Patient adherence to alectinib treatment
Time frame: Through study completion, an average of 2 years
Number of adverse events (AE) related to plasma concentration and dose increases
Time frame: Through total study completion, after 12 months of follow-up
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
Time frame: Questionnaires will be filled in at baseline and every 3 months thereafter through study completion, an average of 2 years.
European Quality of Life Five Dimensions with five levels (EQ-5D-5L) questionnaire
Time frame: Questionnaire will be filled in at baseline and every 3 months thereafter through study completion, an average of 2 years.
Incremental cost-effectiveness ratio (ICER)
Time frame: Through total study completion, after 12 months of follow-up
Alectinib M4 protein
Time frame: Through total study completion, after 12 months of follow-up
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2024.
- Derived from this study: PubMed 36969063Meertens M, Muntinghe-Wagenaar MB, Sikkema BJ, Lopez-Yurda M, Retel VP, Paats MS, Ter Heine R, Schuuring E, Timens W, Touw DJ, van Boven JFM, de Langen AJ, Hashemi SMS, Hendriks LEL, Croes S, van den Heuvel MM, Dingemans AC, Mathijssen RHJ, Smit EF, Huitema ADR, Steeghs N, van der Wekken AJ. Therapeutic drug monitoring guided dosing versus standard dosing of alectinib in advanced ALK positive non-small cell lung cancer patients: Study protocol for an international, multicenter phase IV randomized controlled trial (ADAPT ALEC). Front Oncol. 2023 Mar 9;13:1136221. doi: 10.3389/fonc.2023.1136221. eCollection 2023.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
A.J. van der Wekken, PhD principal investigator
University Medical Center Groningen
8 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Alectinib in people with Drug Monitoring and Carcinoma, Non-Small-Cell Lung, run by University Medical Center Groningen at 8 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Netherlands, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact M.B. Muntinghe-Wagenaar, Msc (+31503616161, adaptalec@umcg.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median progression free survival (mPFS) (time frame: mPFS will be assessed through study completion, after 12 months of follow-up.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05525338, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2024.