The primary objective of the study is to determine the mean prediction error (MPE) and mean absolute prediction error (MAPE) of the area under the plasma concentration-time curve (AUC) of carboplatin after adjusted dosing for high BMI (BMI >= 25…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the mean prediction error and the mean absolute
prediction error in obtaining the target AUC of carboplatin using the new
dosing algorithm.
Secondary outcome
Secondary endpoints are additional pharmacokinetic parameters (including
clearance, half life,) of carboplatin using the new dosing algorithm, the
relationships between the clearance of carboplatin and the serum cystatine C
value and the 24-hour urinary clearance, and safety of treatment defined as
treatment-related toxicity, toxicity-related hospitalization and
toxicity-related dose adjustments
Background summary
Carboplatin is an alkylating anticancer drug that is used for the treatment of
various types of cancer, including non-small cell lung cancer (NSCLC), small
cell lung cancer (SCLC), malignant mesothelioma, ovarian cancer, and breast
cancer.
Carboplatin is excreted for approximately 75% in the urine as unchanged drug
within 24 hours after administration, and its clearance is proportional to the
glomerular filtration rate (GFR). Since carboplatin is highly eliminated by the
kidneys, the dose needs to be adjusted for renal dysfunction. There are several
formulas that can be used to calculate the individual dose of carboplatin. The
Calvert formula [dose = target AUC x (GFR + 25)] is internationally the most
widely used. Herein, the GFR is generally calculated as the estimated
creatinine clearance (CrCl), as calculated by the Cockcroft-Gault formula (GFR
= CrCl = [140 - age] x weight x 0.85 [if female] / 0.815 / serum creatinine).
The Cockcroft-Gault formula is very well suitable to calculate the CrCl in
patients with normal weight, and in patients with serum creatinine values above
the lower limit of normal (~60 µmol/L). However, in both obese patients and
patients with low serum creatinine values, the Cockcroft-Gault equation gives
an overestimation of the CrCl. Consequently, using an overestimated CrCl value
in the Calvert equation, results in a potential serious overdose of
carboplatin, with increased risk for toxicity.
To overcome this problem, we have developed a new dosing algorithm for the
dosing of carboplatin which is based on the latest evidence and available
guidelines. This dosing algorithm uses:
1] the adjusted ideal body weight instead of actual weight for patients with
BMI >= 25 kg/m2
2] a serum creatinine value of 60 µmol/L in patients with serum creatinine < 60
µmol/L, and
3] maintains a maximal calculated (according to the Cockcroft and Gault
formula) renal function of GFR = 125 ml/min
The aim of this study is to prospectively evaluate the pharmacokinetics and
safety of carboplatin after adjusted dosing for high BMI (BMI >= 25 kg/m2), low
serum creatinine (serum creatinine < 60 µmol/L), and maximal renal function
(GFR = 125 ml/min).
Study objective
The primary objective of the study is to determine the mean prediction error
(MPE) and mean absolute prediction error (MAPE) of the area under the plasma
concentration-time curve (AUC) of carboplatin after adjusted dosing for high
BMI (BMI >= 25 kg/m2), low serum creatinine (serum creatinine < 60µm/L), and
maximal renal function (GFR = 125 ml/min).
Secondary objectives are:
- to determine the safety of carboplatin after adjusted dosing for high BMI,
low serum creatinine, and maximal renal function
- to determine the relationship between the measured creatinine clearance, as
measured by collection of a 24-hour urine sample, and the pharmacokinetics of
carboplatin after adjusted dosing for high BMI, low serum creatinine, and
maximal renal function
- to determine the correlation between the measured 24-hour urinary creatinine
clearance and the calculated clearance using the adjusted Cockcroft-Gault
formula (adjusted for high BMI, low serum creatinine and maximal renal function)
- to determine the relationship between serum cystatine C and the
pharmacokinetics of carboplatin
Study design
This is an prospective, pharmacokinetic, single-centre study.
Eligible patients will be treated for their cancer according to routine
clinical practice and standard protocols and treatment regimens. The dose of
carboplatin to be administered will be calculated according to the modified
Cockcroft-Gault formula, i.e.: in patients with BMI >= 25 kg/m2 the dose will be
calculated using the adjusted ideal body weight in stead of actual weight; in
patients with serum creatinine of < 60 µmol/L the dose will be calculated using
a serum creatinine value of 60 µmol/L instead of actual serum creatinine; and
in patients with a calculated GFR of > 125 ml/min, the dose will be calculated
maintaining a maximum GFR of 125 ml/min (figure 1).
In 24 patients, on the first day of cycle 1 of treatment, an additional four
blood samples will be obtained for pharmacokinetic purposes. Furthermore, these
patients will be asked to provide a 24-hour urine sample the day before start
of treatment in order to determine the measured creatinine clearance. In
addition, safety (i.e. haematological and non-haematological toxicity) of each
cycle of treatment will be assessed.
Study burden and risks
All patients will be treated according to standard protocols and treatment
regimens. On day 1 of cycle 1 an additional 4 blood samples (8 ml heparinized
collection tubes) will be obtained for pharmacokinetic purposes at the end of
infusion, and at t = 1 h, 2.5 h and 5 h after the end of the infusion.
Furthermore, this blood will be used to determine the cystatine C value. These
blood samples will be obtained using a venflon, which requires one extra venous
puncture. There is a minimal risk that the venflon may cause slight irritation
or thrombophlebitis. Furthermore, these 24 patients will be asked to provide a
24-hour urine sample the day before start of treatment. this sampling takes
time for the patient, but is not associated with any risks. All other visits
and laboratory investigations are standard care.
Wagnerlaan 55
arnhem 6815AD
NL
Wagnerlaan 55
arnhem 6815AD
NL
Listed location countries
Age
Inclusion criteria
- any type of histologically or cytologically proven solid tumor for which treatment with carboplatin is indicated
- to be treated with carboplatin with a target AUC of 4, 5 or 6
- age 18 years or older
- WHO status 0 - 2
- adequate bone marrow and liver function defined as
o haemoglobin >= 6.0 mmol/L
o white blood cell count >= 3.0 * 109/L
o absolute neutrophil count (ANC) >= 1.5 * 109/L
o platelets >= 100/L
o bilirubin <= 1.5 times ULN
o ALAT and ASAT <= 2.5 times ULN (in case of liver metastases <= 5.0 times ULN).
- estimated life expectancy of at least 12 weeks
Exclusion criteria
- Treatment with carboplatin with a target AUC of <4
- active clinically serious infection
- history of a kidney allograft
- pregnant
- patients not suitable for follow-up
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 | EUCTR2014-000234-33-NL |
| ClinicalTrials.gov | NCT02103244 |
| CCMO | NL47559.091.14 |