Primary objective is to investigate the percentage of patients with k-ras mutant advanced or metastatic colorectal cancer free from progression and alive after 12.5 weeks after the first dose of cetuximab (i.e., 14 weeks after the scan at baseline…
ID
Source
Brief title
Condition
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The percentage of patients with k-ras mutant advanced or metastatic colorectal
cancer free from progression and alive after 12.5 weeks after the first dose of
cetuximab (i.e., 14 weeks after the scan at baseline at start of simvastatin)
in the presence of simvastatin.
Secondary outcome
- Safety of the combination of cetuximab and simvastatin in these patients
- Overall survival
- Progression free survival
- Objective response rate
- Correlation between skin toxicity and anti-tumor response
Background summary
Recent studies have shown that cetuximab in metastatic CRC is an effective
treatment only in patients with wild-type k-ras tumors. In case of mutant type
k-ras, currently no treatment is available after progression on 1st and 2nd
line treatment. In order to create a 3rd line treatment for these patients, we
test the addition of simvastatin to cetuximab, thereby trying to inhibit
expression of the mutated k-ras gene.
Statins inhibit production of C15 and C17, products of the mevalonate pathway,
both essential for post-translational modification of k-ras. Therefore, statins
may inhibit the expression of the mutant k-ras phenotype and normalize the
phenotype into k-ras wild type, thereby making the tumor sensitive to
cetuximab.
Study objective
Primary objective is to investigate the percentage of patients with k-ras
mutant advanced or metastatic colorectal cancer free from progression and alive
after 12.5 weeks after the first dose of cetuximab (i.e., 14 weeks after the
scan at baseline at start of simvastatin) in the presence of simvastatin.
Secondary objectives are to investigate OS, ORR, PFS, safety of simvastatin
combined with cetuximab in this population, correlation between skintoxicity
and anti-tumor response. We also test some possible biomarkers, predictive and
prognostic markers for treatment with cetuximab.
Study design
Single arm, multicenter, phase II study in a Simon two stage design.
Intervention
Weekly infusions of panitumumab and daily use of simvastatin.
Study burden and risks
All patients have to visit the hospital weekly for cetuximab infusions and
laboratory tests. Infusion of cetuximab will take approximately two hours.
It could be possible that patients experience toxicity of this treatment
without having anti-tumor response. Cetuximab may lead to diarrhea and
electrolyte disturbances and possibly skintoxicity, although this is considerd
to occur only in those patients who experience benifit of cetuximab.
Toxicity of simvastatin is rare and usually mild according to the literature.
Possible side-effects may be myopathy, elevations of liver enzymes and, in rare
cases, rhabdomyolyse.
albinusdreef 2
2333ZA Leiden
NL
albinusdreef 2
2333ZA Leiden
NL
Listed location countries
Age
Inclusion criteria
- Advanced or metastatic colorectal cancer failing prior 5FU, oxaliplatin and irinotecan
- Mutation in codon 12, 13 or 61 of k-ras gene on tumor sample
- Adequate condition (WHO 0-2)
- Adequate organ function
- Written informed consent
- Age >= 18 years
- Progressive disease in the past 3 months
Exclusion criteria
- Prior EGFr inhibiting therapy
- Symptomatic brain metastasis
- Using verapamil or amiodarone
- Symptomatic hypothyroidism
- History of interstitial lung disease
- History of toxicity during statin use
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
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 | EUCTR2009-017384-42-NL |
| CCMO | NL30642.058.10 |