Since imatinib easily and rapidly dissolves at pH 5.5 or less, a lack of gastric acid secretion might be causing the decreased exposure in the patients that underwent major gastrectomy. Therefore we would like to study if the exposure to imatinib in…
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
- Gastrointestinal therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess the effect of Coca*Cola on the exposure to imatinib in patients with
major gastrectomy.
Secondary outcome
To assess the effect of Coca*Cola on the frequency and severity of the adverse
events reported while on imatinib therapy
(safety parameter; study is not powered for a significant result)
Background summary
Imatinib is registered for patients with cKIT (CD 117) positive
unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST)
as well as for adjuvant treatment of adult patients who are at risk for relapse
following resection of cKIT positive GIST.
Imatinib is well absorbed after oral administration with Cmax within 2*4 hours
post*dose and with a bioavailability of 98%. The elimination half*live of
imatinib is approximately 18 hours. Imatinib exposure (AUC) increases
proportionally with increasing doses ranging from 25 *1000 mg.
The most common sites for GIST to occur are the stomach (60*70%) and proximal
small intestines (20*25%). Therefore patients with GIST often have altered GI*
tract due to tumor resection or palliative surgery which might affect imatinib
exposure. Indeed, Yoo et al. showed that steady state imatinib trough levels in
patients with advanced GISTs after major gastrectomy are lower compared to
patients with a previous wedge resection or without gastric surgery. Patients
that underwent major gastrectomy had an average imatinib plasma trough levels
below 1000 µg/L. This while imatinib trough levels above 1000 µg/L are
correlated to more beneficial treatment outcomes (longer Progression Free
Survival).
Study objective
Since imatinib easily and rapidly dissolves at pH 5.5 or less, a lack of
gastric acid secretion might be causing the decreased exposure in the patients
that underwent major gastrectomy. Therefore we would like to study if the
exposure to imatinib in patients after major gastrectomy can be improved by
creating a more acidic environment for absorption through combining imatinib
intake with Coca*Cola.
Study design
Phase I post registration prospective, open*label, two*period, cross*over,
randomised, intervention pharmacology study in patients with GIST
Intervention
For 1 week the patient will be asked to take their daily imatinib dosage with
150 mL of Coca-Cola instead of water.
Study burden and risks
Risk assessment is negligible.
Imatinib is well tolerated in doses up to 800 mg daily in the treatment of
GIST. In this study we include patients who are currently treated with imatinib
or who will start imatinib therapy at a standard dose.The dose will not be
modified for study purposes. The only intervention in this study is the intake
of imatinib with Coca*Cola, which might increase the exposure. Since these
patients previously underwent major gastrectomy, their exposure after ingestion
with Coca*Cola is not likely to be significant higher than the exposure to
imatinib in the general population without major gastrectomy. Moreover, in the
phase I studies dose limiting toxicities were only encountered at dosages >
1000mg imatinib. Participating patients will be monitored for adverse events,
therefore we feel that it is safe to perform this study in this population.
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
1. Male or female patients >= 18 years of age
2. Patients with GIST, who previously underwent major gastrectomy
3. Eastern Cooperative Oncology Group (ECOG) performance
status (PS) of 0*1
4.Already selected to receive imatinib therapy in a dose of 400*800mg imatinib daily, as judged by the treating physician and with respect for and in agreement with the registration guidelines
5. Subject is able and willing to sign the Informed Consent Form prior to screening
Exclusion criteria
1. Concomitant administration of any anti*cancer therapies (e.g. chemo*therapy, other targeted therapy, experimental drug, etc) other than imatinib
2. Concomittant use of medication which strongly inhibits or induces CYP3A4
3. Refractory nausea and vomiting, malabsorption with other causes than gastrectomy or external biliary shunt that would preclude adequate absorption.
4. Unwillingness to use Coca*Cola
5. Inability to comply with the requirements of the protocol
6. Inability to understand the nature and extent of the study and the procedures required
7. Participation in a drug study within 60 days prior to the first day of this 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 | EUCTR2014-001044-38-NL |
| CCMO | NL49001.091.14 |