Primary objective is to demonstrate a 25% reduction of the intra-tumoral concentrations of paclitaxel in cycle five compared to cycle one in oesophageal cancer patients. Secondary objectives are: 1) To correlate the intra-tumoral concentrations of…
ID
Source
Brief title
Condition
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary objective is to demonstrate a 25% reduction of the intra-tumoral
concentrations of paclitaxel in cycle five compared to cycle one in oesophageal
cancer patients.
Secondary outcome
1) To correlate the intra-tumoral concentrations of paclitaxel with
pharmacokinetic paclitaxel parameters in plasma (i.e. AUC, CL, Cmax and tmax)
per cycle. 2) To compare the concentrations of paclitaxel in tumor tissue
compared to normal appearing mucosa. 3) To evaluate and to correlate toxicity
to intra-tumoral paclitaxel concentrations. 4) To correlate tumor response with
intra-tumoral paclitaxel concentrations
Background summary
Paclitaxel is a widely used chemotherapeutical agent and a known inducer of
multidrug resistance. One of the major factors of the paclitaxel resistance are
structural changes in efflux-pumps and microtubule network. Preliminary data
show that there is only a weak correlation between the plasma paclitaxel
pharmacokinetics and the effectiveness of treatment. Also there is a lack of
knowledge about the correlations between systemic and intra-tumoral paclitaxel
concentrations in vivo. While this could explain the relationship between
pharmacokinetics and effectiveness (pharmacodynamics). A decline of
intra-tumoral concentrations over time could be the first sign of the
development of drug resistance by the tumor. In this exploratory study we will
investigate the relationship between plasma and intra-tumoral paclitaxel
concentrations over time.
Study objective
Primary objective is to demonstrate a 25% reduction of the intra-tumoral
concentrations of paclitaxel in cycle five compared to cycle one in oesophageal
cancer patients. Secondary objectives are: 1) To correlate the intra-tumoral
concentrations of paclitaxel with pharmacokinetic paclitaxel parameters in
plasma (i.e. AUC, CL, Cmax and tmax) per cycle. 2) To compare the
concentrations of paclitaxel in tumor tissue compared to normal appearing
mucosa. 3) To evaluate and to correlate toxicity to the intra-tumoral
concentrations. 4) To correlate tumor response with intra-tumoral paclitaxel
concentrations
Study design
This is a single centre pharmacokinetic study.
Study burden and risks
Patients with metastatic or locally advanced oesophageal cancer will be treated
with weekly carboplatin and paclitaxel, as standard of care. Patients will be
treated at daytime (no hospital admission required), during the first and fifth
cycle pharmacokinetic blood withdrawals (5x 4ml, 20ml in total) and biopsies of
oesophageal cancer and normal appearing mucosa will be performed. Amount of
possible biopsies will be determined by the performing gastroenterologist; an
estimate of 4-8x (6mm (mean) diameter) tissue samples of tumor and normal
appearing mucosa will be taken. The amount of tissue samples that will be taken
is comparable to the amount taken by an upper endoscopy for standard diagnostic
purpose. The number of site visits is comparable to standard treatment with
paclitaxel and carboplatin. Patients do not benefit individually from this
study. The main risk anticipated is: a small risk of bleeding or aspiration as
result of taking biopsies by upper endoscopy.
Groene Hilledijk 301
Rotterdam 3075 EA
NL
Groene Hilledijk 301
Rotterdam 3075 EA
NL
Listed location countries
Age
Inclusion criteria
* Age * 18 years
* Oesophagus carcinoma
* WHO Performance Status 0-1
* Treatment with weekly paclitaxel and carboplatin is indicated
* Written informed consent
* Patients with safely accessible tumor by upper endoscopy
* No concurrent medication or supplements which can interact with paclitaxel during the study period
Exclusion criteria
* Pregnant or lactating patients
* Previously treatment with radiotherapy on the oesophagus
* Patients who are unable to undergo upper endoscopy
* Patients with a stenosing oesophagus carcinoma prohibiting upper endoscopy
* Contra-indication for the use of midazolam and/or fentanyl (e.g. neuromuscular diseases, severe cardiac/pulmonary disease)
* Bilirubin > 1.5 x ULN, ASAT > 5x ULN, ALAT >5x ULN
* Serum creatinin > 2 x ULN and/or creatinin clearance < 45 mL/min (calculated with Cockroft-Gault formula)
* Patients with evidence or history of any bleeding diathesis, irrespective of severity
* Symptomatic CNS metastases or history of psychiatric disorder that would prohibit the understanding and giving of informed consent.
* Serious illness or medical unstable condition prohibiting adequate treatment and follow-up.
Design
Recruitment
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 |
|---|---|
| CCMO | NL59789.078.16 |