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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitair Medisch Centrum Groningen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08], Diseases [C] - Neoplasms [C04]

Trial duration

23 Mar 2022 → ongoing

Decision date (initial)

2024-10-31

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-506886-76-00

EudraCT number

2020-001737-13

ClinicalTrials.gov

NCT05525338

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacoeconomic, Therapy, Pharmacokinetic, Safety

The primary objective will be a prolonged mPFS for the TDM-guided dosing cohort versus the standard fixed dosing cohort in the group of patients with an alectinib Cmin below the threshold of <435 ng/mL.

Secondary objectives 9

1. Functioning and safety of TDM
2. Overall response rates (ORR)
3. Median overall survival (mOS)
4. Intracranial PFS
5. Physician adherence
6. Toxicity (also in relationship to alectinib plasma concentrations and dose increases)
7. Quality of life
8. Cost-effectiveness
9. Alectinib M4-concentrations

Conditions and MedDRA coding

ALK positive non-small cell lung cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Patients with locally advanced or metastatic NSCLC (stage IIIB to stage IV by AJCC 8th)
2. Male or female >=18 years old
3. ECOG Performance Status of 0-4
4. Histologically or cytology confirmed NSCLC
5. Documented ALK rearrangement based on an EMA approved test
6. Patients can either be chemotherapy-naïve or have received one line of platinumbased chemotherapy
7. 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.
8. Measurable disease (by RECIST criteria version 1.1) prior to the first dose of study treatment
9. Signed written Institutional Review Board (IRB)/Ethical Committee (EC) approved informed consent form, prior to performing any study-related procedures.
10. Observational other studies are allowed for patients included in this study
11. Local radiotherapy is allowed for pain

Exclusion criteria 4

1. Any significant concomitant disease determined by the investigator to be potentially aggravated by the investigational drug
2. 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)
3. 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.
4. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 10

1. 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.
2. Physician adherence to TDM advice. This will be measured as the percentage of dose recommendations that are implemented by the treating physicians.
3. 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.
4. 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.
5. 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.
6. Patient adherence. This will be estimated by pill counts of returned medication as well as a patient diary on drug intake.
7. 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.
8. 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.
9. Cost-effectiveness. This will be determined by the incremental cost-effectiveness ratio based on costs and quality adjusted life-years (QALYs)
10. Alectinib-M4 concentrations. These will be measured in the alectinib plasma samples.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitair Medisch Centrum Groningen

Sponsor organisation

Universitair Medisch Centrum Groningen

Address

Hanzeplein 1

City

Groningen

Postcode

9713 GZ

Country

Netherlands

Scientific contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

Longoncologie UMCG - dr AJ van der Wekken

Public contact point

Organisation

Universitair Medisch Centrum Groningen

Contact name

Longoncologie UMCG - dr AJ van der Wekken

Locations

2 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications