|- candidate number||25649|
|- NTR Number||NTR6183|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||9-dec-2016|
|- Secondary IDs||N16GEM 2016-004595-22|
|- Public Title||Phase 0 proof of concept trial: determination of the pharmacokinetics after administration of a microdose gemcitabine|
|- Scientific Title||Phase 0 proof of concept study: a clinical pharmacokinetic microdosing trial with gemcitabine|
|- hypothesis||The pharmacokinetics of a therapeutic dose of gemcitabine can be adequatly predicted from the pharmacokinetics of a microdose|
|- Healt Condition(s) or Problem(s) studied||Lung cancer, Ovarian cancer, Pancreatic cancer, Bladder carinoma, Breast cancer|
|- Inclusion criteria||1. Age > 18 years.|
2. Indication for treatment with gemcitabine.
3. Histologically or cytologically confirmed diagnosis of:
a. Locally advanced or metastatic non-small cell lung cancer.
b. Locally advanced or metastatic epithelial ovarian carcinoma.
c. Malign mesothelioma
4. Able and willing to give written informed consent.
5. WHO performance status of 0 or 1.
6. Able and willing to undergo blood sampling for PK analysis.
7. All toxicities related to prior treatment should have resolved to CTCAE grade 1 or less.
8. Willing and able to comply with study restrictions and to remain at the study center for the required duration
9. Adequate organ system function.
|- Exclusion criteria||Subjects will not be eligible for study entry if any of the following criteria are met:|
1. Prior chemotherapy, radiotherapy, radio immunotherapy, or immunotherapy within 7 days of the first dose of study treatment
2. Known hypersensitivity to gemcitabine.
3. Presence of known brain metastases or active central nervous system (CNS) disease.
4. Prior treatment with gemcitabine within 30 days of the first dose.
5. New York Heart Association Class 3 or 4 heart disease, active ischemia, or any uncontrolled, unstable cardiac condition for which treatment for the condition is indicated but is not controlled despite adequate therapy, including angina pectoris, cardiac arrhythmia, hypertension, congestive heart failure or myocardial infarction within the previous 26 weeks.
6. Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for the study.
7. Active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant at the time of treatment.
8. Pregnant or lactating.
9. Known positive test result for hepatitis B surface antigen (HBsAg) or hepatitis C antibodies (HC Ab) or has a known positive test result for human immunodeficiency virus (HIV) or a history of HIV disease.
10. Serious medical or psychiatric condition that, in the opinion of the Investigator, should preclude the patient from participating in the study.
|- mec approval received||no|
|- multicenter trial||no|
|- Type||Single arm|
|- planned startdate ||1-mrt-2016|
|- planned closingdate||1-mrt-2017|
|- Target number of participants||10|
|- Interventions||Administration of a microdose (100 ug) of gemcitabine|
|- Primary outcome||The main study parameters will be the concentration of gemcitabine in patient plasma. Pharmacokinetic parameters will be calculated from the acquired data.|
|- Secondary outcome||- Determination of plasma concentrations with LC-MS/MS.|
- Investigate the intracellular effect of gemcitabine after administration of a microdose and after administration of a therapeutic dosage.
|- Timepoints||Blood will be drawn at both day 1 and day 2 at the following timepoints:|
t=0 (predose), t=15 min (1/2th of infusion), t=30 min (end of infusion), t=45 min, t=60 min, t=75 min, t=90 min, t=105 min, t=2 h, t=4 h, t=8 h.
|- Trial web site||NKI-AvL|
|- CONTACT FOR PUBLIC QUERIES||Prof. dr. J.H.M. Schellens|
|- CONTACT for SCIENTIFIC QUERIES||Prof. dr. J.H.M. Schellens|
|- Sponsor/Initiator ||Antoni van Leeuwenhoek |
(Source(s) of Monetary or Material Support)
|Antoni van Leeuwenhoek |
|- Brief summary||This is a phase 0 prospective, single-center, open-label microdosing study. Eligible patients receive a microdose (100 ìg) on day 1 and a therapeutic dose (1000 – 1250 mg/m2) of gemcitabine on day 2. The therapeutic dosage that is given on the second day of the study is not part of the study medication as patients receive gemcitabine therapy as part of standard medical care. Blood will be drawn for pharmcokinetic reserach at 11 time points a day. The pharmacokinetic profile of the microdose will be compared to the pharmacokinetic profile of the therapeutic dose.|
|- Main changes (audit trail)|
|- RECORD||9-dec-2016 - 5-mrt-2017|