Individualized pemetrexed dosing in patients with non-small cell lung cancer or mesothelioma based on renal function to improve treatment response - The IMPROVE-I, -II and -III studies

Phase 2

Recruiting

Conditions: asbestos cancer
lung cancer
10038666

Registration Number: NL-OMON54624

Lead Sponsor: Radboud Universitair Medisch Centrum

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 100

Inclusion Criteria

IMPROVE-I,
1. >=18 years old
2. Eligible for treatment with pemetrexed-based chemotherapy based on indication
3A. For the first three patients (cohort 1): estimated creatinine clearance of
30-45 mL/min
3B. For every next patient (cohort 2): estimated creatinine clearance <45ml/min
4. ECOG performance score of 0-2
5. Subject is able and willing to sign the Informed Consent Form
IMPROVE-II
1. >=18 years old
2. Eligible for treatment with pemetrexed-based chemotherapy
3. Creatinine clearance >45ml/min
4. ECOG performance score of 0-2
5. Subject is able and willing to sign the Informed Consent Form,
IMPROVE-III
1. >=18 years old
2. Planned for treatment with pemetrexed-based chemotherapy
3. ECOG performance score of 0-2
4. Subject is able and willing to sign the Informed Consent Form

Exclusion Criteria

IMPROVE-I, -II and -III
1. Conditions that affect haemostasis in a way that blood drawing is
complicated (to be assessed by physician)
2. Contraindications for treatment with pemetrexed in line with the SmPC
(except for creatinine clearance <45 ml/min in IMPROVE-I)
a.Hypersensitivity to the active substance or to any of the excipients
b.Pregnancy or lactation
c. Concomitant yellow fever vaccine
3. The presence of clinically relevant pharmacokinetic interactions, according
to the current SmPC
4. Obesity (defined as a body mass index (BMI) >40 kg/m2)
5. Limb amputation
6. Use of trimethoprim and/or cimetidine
additional for IMPROVE-I:
7. Baseline absolute neutrophil count <1.5*109/L

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>IMPROVE-I<br /><br>The fraction of patients safely reaching the target dose in combination with<br /><br>folinic acid or folinic acid and G-CSF, with the target dose being the dose<br /><br>most likely to result in an AUC of 164 mgh/L.<br /><br><br /><br>IMPROVE-II<br /><br>The fraction (percentage) of patients with attainment of therapeutic exposure<br /><br>defined as an AUC of 164 mgh/l ±25%, with pemetrexed dosing based on renal<br /><br>function versus BSA-based dosing. AUC will be calculated based on the dose and<br /><br>the estimated pemetrexed clearance.<br /><br><br /><br>IMPROVE-III<br /><br>The predictive performance of microdosing for pemetrexed clearance at<br /><br>therapeutic doses by assessing accuracy (MPE) and precision (NRMSE) in<br /><br>reference to full dose pharmacokinetics. </p><br>

Secondary Outcome Measures