The primary objective is to assess the impact of hyperhydration on pemetrexed pharmacokinetics. The secondary objective is to compare the performance of different renal function algorithms to predict pemetrexed pharmacokinetics.
ID
Source
Brief title
Condition
- Respiratory and mediastinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The aim is to assess if there is a relevant and significant difference in
pemetrexed exposure (clearance, Cl) as a result of hyperhydration during
treatment with pemetrexed. A relevant clinical effect is defined a 25%
difference in clearance.
Secondary outcome
As a secondary study parameter, the comparative performance of different renal
function algorithms for the prediction of clearance is assessed.
Background summary
Pemetrexed is a pharmacotherapeutic cornerstone for treatment of non-small cell
lung cancer and mesothelioma. In the Netherlands, approximately 3000 patients
are treated with this drug each year, either as monotherapy or in combination
with cisplatin or carboplatin. Besides dose, renal function is the only
determinant for systemic exposure: with decreasing renal function, systemic
exposure increases accordingly. Since systemic exposure to pemetrexed (area
under the concentration versus time curve (AUC)) is closely related with both
efficacy measures (time to progressive disease) as (severe) toxicity,
individualized dosing is of utmost importance to balance the dual risk of
inefficacy and toxicity associated with treatment. We hypothesize that
hyperhydration, which is given to promote excretion of cisplatin that is
co-administered the first four cycles during combination therapy, causes
augmented clearance of pemetrexed, resulting in decreased pemetrexed exposure.
On the contrary, when in subsequent cycles cisplatin is not administered and
hyperhydration is not performed, higher exposure and increased toxicity may be
observed. Testing this hypothesis will further elucidate the pharmacokinetics
of pemetrexed and may provide new insights regarding renal function as a
determinant for optimal pemetrexed dosing and may be a next step to improved
dosing with this cytotoxic agent.
Study objective
The primary objective is to assess the impact of hyperhydration on pemetrexed
pharmacokinetics. The secondary objective is to compare the performance of
different renal function algorithms to predict pemetrexed pharmacokinetics.
Study design
The design is an observational, prospective, pharmacokinetic study. While this
is an observational design there will be no interventions in therapy.
Study burden and risks
In this study there is no therapeutic intervention, so there is no benefit from
participation in the study. Possible risks associated with the study are
related to drawing a limited number of blood samples (e.g. syncope, hematoma,
bleeding) and are considered negligible. There are no risks related to
treatment outcome, while patients receive standard care. At one occasion, the
patient must stay an extra 6 hours to complete sampling. We designed a limited
sampling strategy to reduce the burden and risks for the patient.
Henri Dunantstraat 1
's-Hertogenbosch 5223 GZ
NL
Henri Dunantstraat 1
's-Hertogenbosch 5223 GZ
NL
Listed location countries
Age
Inclusion criteria
1. *18 years old
2. Planned for treatment with cisplatin/pemetrexed combination therapy followed by pemetrexed maintenance therapy as a part of routine care.
3. Creatinine clearance * 45ml/min
4. Subject is able and willing to sign the Informed Consent Form.
Exclusion criteria
1. Patients that suffer from conditions that affect hemostasis in a way that blood drawing is complicated (to be assessed by physician) are excluded.
Design
Recruitment
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 |
|---|---|
| CCMO | NL62137.028.17 |
| OMON | NL-OMON21433 |