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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-001737-13 | EudraCT Number | ||
| NL9411 | Registry Identifier | Nederlands Trial Register |
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| Name | Class |
|---|---|
| Amsterdam University Medical Center | OTHER |
| Erasmus Medical Center | OTHER |
| Maastricht University Medical Center | OTHER |
| Radboud University Medical Center |
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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).
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| TDM-guided dosing arm | Experimental |
| |
| 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. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alectinib | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | mPFS will be assessed through study completion, after 12 months of follow-up. |
| Measure | Description | Time Frame |
|---|---|---|
| Succesfull Therapeutic Drug monitoring | The percentage of succesfull TDM interventions, in which successful is defines as tartget attainment and manageable toxicity. | 4 to 6 weeks after dose adjustment based on TDM |
| Overall response rate (ORR) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| M.B. Muntinghe-Wagenaar, Msc | Contact | +31503616161 | adaptalec@umcg.nl |
| Name | Affiliation | Role |
|---|---|---|
| A.J. van der Wekken, PhD | University Medical Center Groningen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Gustave Roussy | Not yet recruiting | Villejuif | Val-de-Marne | 94805 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36969063 | Derived | 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. |
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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.
The study protocol will be available after ending of the study and publication of the manuscript ending 5 years after article publication.
For individual participant data meta-analysis
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| OTHER |
| The Netherlands Cancer Institute | OTHER |
| Leiden University Medical Center | OTHER |
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.
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The alectinib Cmin for patients treated in arm B (standard dose arm) will be blinded to participants and care providers
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ORR is the percentage of patients with partial response or complete response, according to RECIST v1.1, of the total treated population.
| 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. | 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. | 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. | 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. | 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 | 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 | 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. | Through total study completion, after 12 months of follow-up |
| Alectinib M4 protein | Alectinib M4 plasmaconcentrations in relation to alectinib plasma concentrations | Through total study completion, after 12 months of follow-up |
| Radboud University Medical Center | Recruiting | Nijmegen | Gelderland | 6525 GA | Netherlands |
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| Maastricht University Medical Center + | Recruiting | Maastricht | Limburg | 6229 HX | Netherlands |
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| The Netherlands Cancer Institute | Recruiting | Amsterdam | North Holland | 1066 CX | Netherlands |
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| Amsterdam University Medical Center | Recruiting | Amsterdam | North Holland | 1105 AZ | Netherlands |
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| Leiden University Medical Center | Recruiting | Leiden | South Holland | 2333 ZA | Netherlands |
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| Erasmus Medical Center | Recruiting | Rotterdam | South Holland | 3015 GD | Netherlands |
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| University Medical Center Groningen | Recruiting | Groningen | 9713GZ | Netherlands |
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| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D008175 | Lung Neoplasms |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C582670 | alectinib |
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