To ascertain whether the pharmacokinetics of gemcitabine in a therapeutic dose can be predicted from the pharmacokinetics of a microdose.
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To study the pharmacokinetics after administration of a microdose and the
pharmacokinetics after administration of a therapeutic dose.
Secondary outcome
To analyse patient plasma with liquid chromatography-mass spectrometry
(LC-MS/MS)
Background summary
Phase 0 microdose studies can be conducted prior to phase 1 in drug development
to study the pharmacokinetics a certain drug. These pharmacokinetics are
thought to predict the pharmacokinetics after administration of a therapeutic
dose. Curretly, 11 phase 0 microdose trials have been published. During such a
trial, it is unknown whether the pharmacokinetics are indeed scalable to the
pharmacokinetics of a therapeutic dose. None of these studies have been
conducted with chemotherapeutics.
Gemcitabine is a drug that can be prescribed for several types of cancer. It is
a chemotherapeutic drug that belongs to the group of antimetabolites.
Gemcitabine is metabolised intracellularly to diphosphate- and
triphosphatenucleosides (dFdCDP and dFdCTP). Gemcitabine triphosphate inhibits
DNA-synthesis by inhibition of ribonucleotide reductase: this enzyme catalyses
the production of deoxynucleoside triphospates (dCTP). Gemcitabine
triphosphates compete with dCTP for DNA incorporation. This incorporation
inhibits DNA sythesis and eventually induces apoptosis.
Study objective
To ascertain whether the pharmacokinetics of gemcitabine in a therapeutic dose
can be predicted from the pharmacokinetics of a microdose.
Study design
This is a phase 0 prospective, single-center, open-label microdosing study.
Eligible patients consecutively receive a microdose (100 *g) and a therapeutic
dose (1000 * 1250 mg/m2) of gemcitabine with a 1-day interval as shown in
Figure 1. Only patients who are qualified for gemcitabine therapy according to
standard of care can enroll in this study. Blood will be drawn for
pharmacokinetic research at 11 time points a day
Intervention
Administration of a microdose
Study burden and risks
A microdose is considered harmless and nontoxic as the administered dose is
just a small portion of the therapeutic dose. Therefore, we qualify the risk of
this study as *low*. This is motivated by the following:
1) The study drug is registered for clinical use.
2) Multiple studies in these patient categories with the study drug have been
performed before.
3) A microdose is considered harmless and non-toxic.
Plesmanlaan 121
Amsterdam 1066 CX
NL
Plesmanlaan 121
Amsterdam 1066 CX
NL
Listed location countries
Age
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 bladder cancer.
c. Malignant 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
1. Known hypersensitivity to gemcitabine.
2. Prior treatment with gemcitabine within 30 days of the first dose.
3. 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.
4. Active, uncontrolled systemic infection considered opportunistic, life threatening, or clinically significant at the time of treatment.
5. 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.
6. Serious medical or psychiatric condition that, in the opinion of the Investigator, should preclude the patient from participating in the study.
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 | EUCTR2016-004595-22-NL |
| CCMO | NL59891.031.17 |