The primary objective of the study is assessment of the dose limiting toxicity (DLT) and maximal tolerated dose (MTD) of docetaxel, oxaliplatin and capecitabine given in combination in patients with advanced cancer of the stomach or the gastro-…
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Determination of MTD and DLT of DOCCS in patients with advanced cancer of
stomach or gastro-esophageal junction.
Secondary outcome
- Determination of preliminary clinical activity of DOCCS
- Pharmacokinetic parameters for determination of the pharmacokinetic of DOCCs
- Determination of circulating tumor cells before start of treatment and after
cycle 1, and to correlate changes with clinical outcome
- Determination of platinum DNA adducts in gastric- and tumortissue, 24 h after
start oxaliplatin (optional)
Background summary
Surgical resection is the primary curative treatment option in gastric cancer,
with or without the combination of adjuvant chemotherapy. If surgery is not
applicable anymore, such as in advance disease, chemo(radio)therapy is
indicated. However, the survival advantage appears to be marginal and there is
no established standard regime, although the ECF schedule, with response rate
about 45% and median overall survival of 9 months, has been popular in Europe.
The current poor prognosis of gastric cancer underscores the need for new and
better treatment modalities, taking into account the toxicity profile and the
administration logistics.
Docetaxel has been shown to be active in the treatment of gastric cancer and is
approved for the treatment of unresectable advanced adenocarcinoma of the
stomach and gastroesophagheal junction in combination with cisplatin and 5-FU.
Oxaliplatin has a favorable toxicity profile compared to cisplatin, which makes
it an attractive alternative. The same accounts for replacement of 5-FU by
capecitabine, with the extra advantage of the patient-convenient route of
administration. Oxaliplatin and capecitabine both in multiple studies have
shown activity in the treatment of gastric cancer.
Based on the extensive experience with combination chemotherapy for gastric
cancer and existing data of the 3 study drugs, we expect to be able to develop
a tolerable chemotherapy combination schedule with docetaxel, oxaliplatin and
capectibine (DOCCS) in therapeutic dosage.
Study objective
The primary objective of the study is assessment of the dose limiting toxicity
(DLT) and maximal tolerated dose (MTD) of docetaxel, oxaliplatin and
capecitabine given in combination in patients with advanced cancer of the
stomach or the gastro-oesophageal junction.
Secondary objectives are:
a) To determine preliminary clinical activity of the DOC combination
b) To establish the effect of functional genetic polymorphisms on the
pharmacokinetics and pharmacodynamics of the DOC combination
c) To assess the frequency of circulating tumor cells detectable in patients
with advanced cancer of stomach or gastro-esophageal junction prior to
initiation of systemic therapy and after one course of therapy and to correlate
these changes with radiological findings and clinical outcome.
d) To assess the feasibility of the analysis of pt-DNA adducts in tissue using
ICP-MS and to determine the minimal amount of tissue needed, and to determine
whether there is a relationship between the amount of pt-DNA adducts in
gastric-, tumor tissue and PBMCs 24 hours after start of the first
administration of oxaliplatin. (optional)
Study design
Non-comparitive, phase I, dose-escalation, multicenter study
Intervention
Treatment consists of:
- Docetaxel as a 1-hour i.v. infusion in a 250 ml 0.9% NaCl solution on day 1,
followed by
- Oxaliplatin as a 2-hour i.v. infusion in a 500 ml 5% glucose solution on day
1,
- Capecitabine p.o. BID on days 1 - 14 in a cycle of 21 days
In total 6 dose levels are defined with escalation of just one study drug at a
time per dose level. The first 3 patients will start in dose level 1. If no or
minimal (grade 0 or 1) toxicity is observed during the first course including 1
week after the last patient has completed course 1, the next three patients may
proceed to dose level 2. The same accounts for subsequent dose levels. No
intrapatient dose escalation will be applied.
If at any dose level one of the 3 patients develops significant toxicity, up to
an additional 3 patients (up to a total of 6) will be treated at the same dose
level. If 2 or more out of 6 exhibit dose limiting toxicity, the maximum
tolerated dose (MTD) will be considered to be the dose given at the previous
lower dose level. This will be the advised dose for the combination schedule of
docetaxel, oxaliplatin and capecitabine. Finally, a minimum of 14 and a maximum
of 25 patients will be treated at the MTD.
Study burden and risks
Several blood samples will be obtained during course 1, which is associated
with a minimal risk. The total number of venapunctures and blood sampling
procedures will be reduced to a minimum, to minimise the patients burden.
Gastric- and tumortissue sampling is optional. The inconvenience will be
minimised by throat anaesthesia and, if the patient wishes so, sedation.
Biopsies taken during gastroscopy may leed to small bleedings, however, these
bleedings generally stop immediately.
Plesmanlaan 121
1066 CX Amsterdam
Nederland
Plesmanlaan 121
1066 CX Amsterdam
Nederland
Listed location countries
Age
Inclusion criteria
1. Patients with advanced, histologically confirmed, adenocarcinoma of the stomach or the gastroesophageal junction
2. Previous (neo)adjuvant chemotherapy with epirubicin, cisplatin, 5-FU or capecitabine is allowed provided that a relapse occurred > 12 months after chemotherapy. Otherwise patients should be chemonaive.
3. Measurable or evaluable non-measurable disease
4. Age 18 years or older
5. Able to swallow and retain oral medication
6. Able and willing to undergo blood sampling for pharmacogenetic and pharmacokinetic analysis, and circulating tumor cells analysis
7. Life expectancy of at least 3 months allowing adequate follow up of toxicity evalution and antitumor activity
8. Minimal acceptable safety laboratory values
a. ANC of 1.5 x 109 /L or higher
b. Platelet count of 100 x 109 /L or higher
c. Haemoglobin level of 6.0 mmol/l or higher - transfusion is permitted
d. Hepatic function as defined by serum bilirubin of less 1.5 x ULN or less, ALT and AST and alkaline phosphatase 2.5 x ULN or less
e. Renal function as defined by serum creatinine 1.5 x ULN or less or creatinine clearance more than 50 ml/min (by Cockcroft-Gault formula).
9. Able and willing to give written informed consent
10. WHO performance status of 0, 1 or 2
Exclusion criteria
1. Known CNS or leptomeningeal metastases (a CT or MRI scan should be done if there is a clinical suspicion of CNS metastases)
2. History of another primary cancer, except curatively treated in situ cervical cancer or resected non-melanoma skin cancer
3. Uncontrolled infectious disease or known HIV, hepatitis B or hepatitis C patients
4. Patients with known alcoholism, drug addiction and/or psychotic disorders in the history that are not suitable for adequate follow up
5. Women who are pregnant or breast feeding
6. Women of childbearing potential who refuse to use a reliable contraceptive method throughout the study
7. Any other medical condition that would interfere with study procedures and/or decrease safety of the protocol treatment.
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 | EUCTR2007-002626-30-NL |
| CCMO | NL17610.031.07 |