Validation of an Adjusted Dosing Algorithm of Carboplatin

Cancer Clinical Trial

Official title:

Pharmacokinetics of Carboplatin After Adjusted Dosing for High BMI, Low Serum Creatinine, and Maximal Renal Function

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02103244
• Other study ID #: CARBMI
• Status: Not yet recruiting
• Phase: Phase 4
• First received: March 26, 2014
• Last updated: April 2, 2014
• Start date: September 2014
• Est. completion date: December 2015

Study information

• Verified date: March 2014
• Source: Rijnstate Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

An adjusted dosing algorithm for the dosing of the anticancer drug carboplatin has been developed, that accounts for high BMI, low serum creatinine values and maximal calculated renal function. The hypothesis is that this new dosing algorithm provides a more accurate and safe dose than dosing according to the old standard of care.

Description:

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. It is mostly given in combination with other chemotherapeutic drugs, but it can also be given as single agent.

Since carboplatin is highly eliminated by the kidneys, the dose needs to be adjusted for renal dysfunction. Furthermore, as there is clear correlation between the area under the concentration-time curve (AUC) of carboplatin and haematological toxicity and response rate, carboplatin is dosed per target AUC. For this, the standard pharmacokinetic formula [dose = clearance carboplatin x target AUC] is used.

the clearance is typically calculated using the cockcroft and gault (C-G) formula. In patients with high weight, or very low serum creatinine values the C-G-formula may overestimate the renal function, resulting in a potential overdose of carboplatin. the new developed dosing algorithm to be studied adjusts for high BMI and low serum creatinine values, in order to provide a more safe dose of carboplatin

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 24
• Est. completion date: December 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• histologically or cytologically proven advanced NSCLC, SCLC or ovarian cancer

• to be treated with carboplatin with a target AUC of 4, 5 or 6

• age 18 years or older

• WHO performance status 0 - 2

• adequate bone marrow and liver function defined as

• haemoglobin = 6.0 mmol/L

• white blood cell count = 3.0 * 109/L

• absolute neutrophil count (ANC) = 1.5 * 109/L

• platelets = 100/L

• bilirubin = 1.5 times ULN

• 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

• pregnancy or breast-feeding

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer

Intervention

Drug:
• Carboplatin
carboplatin will be dosed according to newly developed dosing algorithm.

Locations

Country	Name	City	State
Netherlands	Rijnstate Hospital	Arnhem

Sponsors (1)

Lead Sponsor	Collaborator
Rijnstate Hospital

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	to the determine the mean absolute precision error and the mean prediction error of the AUC of carboplatin after dosing carboplatin according to the new dosing algorithm		1 year	Yes
Secondary	Assessment of the incidence and severity of all adverse events that occurred during treatment with carboplatin	Treatment with carboplatin is associated with adverse drug reactions. As an oncolytic drug, treatment with carboplatin may for example result in myelosupression, infections and/or gastro-intestinal toxicity, that may require hospitalization for treatment of toxicity.; With the new dosing algorithm we hope to provide a better calculation of the appropriate dose for the individual patient, and thereby a safer treatment. Therefore, adverse events of treatment is an important secondary outcome measure that will be assessed.	1 year	Yes