Primary objective:To evaluate the area under the curve of afatinib compared to afatinib concomitantly used with esomeprazole and to afatinib used with esomeprazole 3 hours prior in patients with non-small cell lung cancer.Secondary objective:1.…
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the area under the curve of afatinib compared to afatinib
concomitantly used with esomeprazole and to afatinib used with esomeprazole 3
hours prior in patients with non-small cell lung cancer.
Secondary outcome
1. Other pharmacokinetic outcomes (i.e. clearance, maximum concentration and
time to Cmax).
2. To evaluate the incidence and severity of side-effects of treatment with
afatinib in absence and presence of esomeprazole.
Background summary
In The Netherlands, afatinib is registered for the treatment of advanced lung
cancer. A majority of the patients benefit of the therapy, with lower rates of
cancer cell proliferation. Many cancer patients have gastric complaints such as
reflux and have to use proton pump inhibitors, or get proton pump inhibitors
prescribed to prefent gastric complaints. Concomitant use of afatinib with a
proton pump inhibitor could lower afatinib bio-availability by increasing pH,
and thus preventing absorbtion of afatinib in the intestinal tract.
Nevertheless, to date, this interaction has never been studied.
Study objective
Primary objective:
To evaluate the area under the curve of afatinib compared to afatinib
concomitantly used with esomeprazole and to afatinib used with esomeprazole 3
hours prior in patients with non-small cell lung cancer.
Secondary objective:
1. Other pharmacokinetic outcomes (i.e. clearance, maximum concentration and
time to Cmax).
2. To evaluate the incidence and severity of side-effects of treatment with
afatinib in absence and presence of esomeprazole.
Study design
Open label three-period, randomized, cross-over pharmacokinetic study.
Intervention
Esomeprazole 40mg once daily, in a total of 10 days. Afatinib is taken in
accordance to standard of care. Esomeprazole will be taken concomitant and 3
hours prior afatanib intake, each period for 5 days.
Study burden and risks
Patients will be admitted to the hospital for a total of three days, during
which pharmacokinetic blood withdrawals will be performed. Patients will be
randomized into 2 sequence groups consisting of three phases. In 2 phases
patients are also treated with esomeprazole for a total of 28 days. Patients do
not benefit individually from this study. Major risks to be expected are side
effects of esomeprazole or afatinib for which patients will be observed
carefully.
's-Gravendijkwal 230
Rotterdam 3015CE
NL
's-Gravendijkwal 230
Rotterdam 3015CE
NL
Listed location countries
Age
Inclusion criteria
1. Age >= 18 years
2. Histological or cytological confirmed diagnosis of EGFR-mutated NSCLC
3. WHO Performance Status <= 1
4. Able and willing to sign the Informed Consent Form prior to screening evaluations
5. No concurrent (over the counter) use of other acid reducing drugs (PPIs, H2As and/or antacids), other than esomeprazole 40mg once daily during the study.
6. No concurrent medication or supplements which can interact with esomeprazole or afatinib during the study period (such as PgP-inhibitors/inducers).
7. Abstain from grapefruit, grapefruit juice, herbal dietary supplements, cranberry juice, and herbal tea during the study period.
8. Adequate baseline patient characteristics (complete blood count, and serum biochemistry which involves sodium, calcium, potassium, creatinin, calculation of creatinin clearance (MDRD), AST, ALT, gamma-GT, lactate dehydrogenase (LDH), total bilirubin, albumin, glucose within two weeks prior to the study.
Exclusion criteria
1. Pregnant or lactating patients.
2. Patients with known impaired drug absorption (e.g. gastrectomy and achlorhydria)
3. Known serious illness or medical unstable conditions that could interfere with this study; requiring treatment (e.g. infection, bleedings, uncontrolled hypertension despite optimal medical management, HIV, hepatitis, organ transplants, kidney, cardiac and respiratory diseases).
4. Unwillingness to abstain from acid beverages such as orange juice and cola in the morning during afatinib treatment in this study.
5. Patients who are clinical dependent of use of PPIs or other acid reducing drugs, e.g. due to elevated risk for gastro-intestinal bleeding.
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
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-001284-20-NL |
| CCMO | NL61424.078.17 |