Primary:To identify the recommended dose of sorafenib and of sirolimus for combination therapy in subsequent phase II trials Secondary:1. to determine the safety profile of the combination therapy of sorafenib with sirolimus.2. to determine, if…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Critria for evaluation
Safety profile
The primary end point is to identify the recommended doses for the combination
of sorafenib and sirolimus for subsequent phase II studies.
Evaluation of DLT*s will be done. Adverse events will be scored using CTC AE v3.
Efficacy
There will be a descriptive analysis of proportion of patients with response or
stable disease.
Secondary outcome
not applicable
Background summary
Sirolimus, a raf kinase inhibitor, is a recently registered anti cancer drug
for renal cell cancer. Sorafenib is a mTOR inhibitor. mTOR inhibitors can
induce an anti-tumor effect. The sirolimus - sorafenib combination therapy will
be studied in the present trial in patients with advanced refractory solid
tumours for whom no standard therapy exists. It is hypothesized that the
combination of sorafenib with sirolimus, two targeted drugs, could work
synergistic in inhibiting tumor growth. The reason for choosing sirolimus and
not temsirolimus (CCI-779), another mTOR inhibitor, is that both sorafenib and
sirolimus are tablets for oral use. Temsirolimus can be administered
parenterally only.
Because sorafenib and sirolimus are both metabolized via CYP3A4 the
pharmacokinetics can be influenced by each other. Thus, a close monitoring of
safety and toxicity as well as exact monitoring of pharmacokinetics of
sirolimus and sorafenib will be performed.
Study objective
Primary:
To identify the recommended dose of sorafenib and of sirolimus for combination
therapy in subsequent phase II trials
Secondary:
1. to determine the safety profile of the combination therapy of sorafenib with
sirolimus.
2. to determine, if possible, the Maximum Tolerated Dose (MTD) of sorafenib and
sirolimus in combination therapy
3. to analyze pharmacokinetic PK profiles (AUC, Cmax) during combination
therapy for sorafenib and sirolimus
4. to evaluate efficacy of the combination descriptively (response rate and
rate of stable diseases)
Study design
Mono-centre, open-label, uncontrolled, dose-escalating phase I design
The design includes up to 3 treatment cohorts with 6 patients each.
Intervention
Combination of sorafenib with sirolimus (dose escalating study)
Study burden and risks
This is a phase I study. Sorafenib is registered for the use in renal cell
cancer. Sirolimus is registered for another indication than cancer. The dosages
needed to have clinical effect are well known. In the first cohort of patients
we treat at a lower dosage than the normal dosages used for both sorafenib and
sirolimus. Thus the risk for serious adverse events is limited.
The response rate in phase I studies is 10% in general.
P.O. Box 9101
6500 HB Nijmegen
Nederland
P.O. Box 9101
6500 HB Nijmegen
Nederland
Listed location countries
Age
Inclusion criteria
1. Patients with histological or cytological confirmed advanced solid tumor, which is refractory to standard therapies or for which no standard therapy exists and for which there is a rationale for the therapeutic use of a combination of sorafenib and sirolimus (especially metastic RCC, malignant melanoma, HCC, NSCLC, pancreatic cancer, hormone refractory prostate cancer).
2. Men or women of at least 18 years
3. Patients who have an ECOG status of 0 or 1
4. Patients who have a life expectancy of at least 12 weeks
5. Adequate bone marrow, liver and renal function
Exclusion criteria
1. History of serious cardiac disease
2. Active clinically serious bacterial, viral or fungal infections (> grade 2).
3. Known history of human immunodeficiency virus (HIV) infection or chronic hepatitis B or C.
4. Clinically symptomatic brain or meningeal metastasis.
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 | EUCTR2006-006454-10-NL |
| CCMO | NL15796.091.06 |