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
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The Ctrough of alectinib in patients with NSCLC treated with alectinib when
concomitantly taken with a continental breakfast, low-fat yoghurt as breakfast
or at lunchtime.
Secondary outcome
- The current food intake with alectinib;
- The occurrence of patient-reported toxicity when alectinib is taken with a
continental breakfast, a low fat diet and lunchtime;
- A pharmacokinetic model of alectinib when alectinib is taken with a
continental breakfast.
- Analysis of a possible drug-drug interaction between alectinib and
semaglutide.
Background summary
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. The
anti-obesity drug semaglutide could be used as treatment for severe
alectinib-induced weight gain. However, the possible pharmacokinetic effect
semaglutide has on alectinib due to delayed gastric emptying ought to be
investigated before this drug can be co-administered on a larger scale.
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 2.0 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
- 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 2.0 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.
Doctor Molewaterplein 40
Rotterdam 3015GD
NL
Doctor Molewaterplein 40
Rotterdam 3015GD
NL
Listed location countries
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;
• Willing to follow dietary restrictions.
Exclusion criteria
• Unable to draw blood for study purposes;
• 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
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2022-003275-42-NL |
| CCMO | NL78079.078.23 |
| OMON | NL-OMON28490 |