To investigate the effect of various dietary interventions and co-administration of subcutaneous semaglutide on the pharmacokinetics of alectinib in NSCLC patients.
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Health condition
Non-smalle cell lung carcinoma (NSCLC).
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
"The primary outcome will be the change in Ctrough of alectinib during phase B or C compared to phase A." into "The primary outcome will be the change in Ctrough of alectinib during phase B, C and D compared to phase A.".
Secondary outcome
Toxicity and the mean the range of the macronutrients in the current intake and a pharmacokinetic model.
Background summary
Rationale: Alectinib (Alecensa) is a second generation small-molecule kinase inhibitor, registered for ALK-positive, metastatic non-small cell lung cancer (NSCLC). Because alectinib’s plasma trough concentration (Ctrough) is correlated with patients’ progression-free survival, it is important to optimize its bioavailability. Compared to fasted intake, alectinib’s exposure increases with >200% when taken with a high-fat meal. In daily practice, patients are therefore recommended to take alectinib twice daily with a (high-fat) meal. However, 37% of patients does not reach the vital Ctrough. Additionally, (extreme) weight gain is an important side effect of alectinib treatment. It is currently unknown if there are good (and healthy) alternatives for a high-fat meal to increase alectinib’s absorption and to optimize its treatment. Objective: To investigate the effect of different diet interventions on the pharmacokinetics of alectinib in NSCLC patients. Study design: This study is an interventional, randomized, three-period cross-over pharmacokinetic study in which alectinib will be taken twice daily (BID) for seven days in combination with: - in phase A (control phase): a normal diet, c.q. continental breakfast and normal dinner; - in phase B: a low-fat diet, c.q. 200 grams low-fat yoghurt as breakfast, and normal dinner; - in phase C: a normal diet with different intake times, c.q. lunch and dinner. After the 7th day of each phase, patients are asked to withdraw blood in the morning, prior to alectinib intake to collect a Ctrough sample. Optionally, in phase A, patients are admitted for a 10-hour pharmacokinetic sampling of in total 13 samples. Study population: Adult patients with NSCLC who are treated with alectinib. Main study parameters/endpoints: The primary outcome will be the change in Ctrough of alectinib during phase B or C compared to phase A. Secondary outcomes will be the occurrence of (patient reported) toxicity, the current intake with alectinib and a pharmacokinetic model. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The risk of blood withdrawal is negligible. In addition, the risk for altered alectinib concentrations in this short period is also considered to be negligible. The burden for patients is also limited as only a Ctrough sample is taken and the 10h PK-sampling is optional.
Study objective
To investigate the effect of various dietary interventions and co-administration of subcutaneous semaglutide on the pharmacokinetics of alectinib in NSCLC patients.
Study design
This study is an interventional, randomized, three-period cross-over pharmacokinetic study in which alectinib will be taken twice daily (BID) for seven days in combination with:
- in phase A (control phase): a normal diet, c.q. continental breakfast and normal dinner;
- in phase B: a low-fat diet, c.q. 200 grams low-fat yoghurt as breakfast, and normal dinner;
- in phase C: a normal diet with different intake times, c.q. lunch and dinner.
- in phase D: a normal diet, c.q. continental breakfast and dinner, with co-administration of semaglutide 2.4 mg s.c..
After the 7th day of each phase, patients are asked to withdraw blood in the morning, prior to alectinib intake to collect a Ctrough sample. Optionally, in phases A and D, patients are admitted for a 10-hour pharmacokinetic sampling of in total 13 samples.
Intervention
Different diatairy intake with alectinib.
- in phase B: a low-fat diet, c.q. 200 grams low-fat yoghurt as breakfast, and normal dinner;
- in phase C: a normal diet with different intake times, c.q. lunch and dinner.
- in phase D: a normal diet, c.q. continental breakfast and dinner, with co-administration of semaglutide 2.4 mg s.c..
Study burden and risks
The risk of blood withdrawal is negligible. In addition, the risk for altered alectinib concentrations in this short period is also considered to be negligible. The burden for patients is also limited as only a Ctrough sample is taken and the 10h PK-sampling is optional.
Age
Inclusion criteria
- • Age: ≥18 years;
- • Able to understand the written information and willing to give informed consent;
- • Diagnosed with metastatic NSCLC and (are planned to) receive treatment with alectinib (Alecensa);
- • Use of alectinib of at least 14 days, to guarantee steady-state, and expected to continue treatment until end of study period;
- • WHO performance score with a maximum of 2; • Willing to follow dietary restrictions.
Exclusion criteria
- • Unable to draw blood for study purposes;
- • Pregnant or lactating women;
- • Not willing/able to not use medication which are a substrate for Pgp and have a small therapeutic window during study period, e.g. digoxine, dabigatran, sirolimus, everolimus, topotecan, nilotinib and lapatinib. Due to P-gp inhibition of alectinib;
- • Not willing/able to not use medication which are a substrate for Pgp and have a small therapeutic window during study period, e.g. rosuvastatine, sulfasalazine, methotrexaat, topotecan, lapatinib and mitoxantron. Due to BRCP inhibition of alectinib;
- • Unwillingness to abstain from any other food or drinks than the prescribed restrictions 1 hour before and 2 hours after intake of alectinib at the pharmacokinetic sampling day; • Patients with known impaired drug absorption (e.g. gastrectomy and achlorhydria); • Allergic to compounds in yoghurt.
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL9702 |
| EudraCT | 2022-003275-42 |
| CCMO | NL78079.078.23 |
| OMON | NL-OMON54011 |