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A multi-institutional open label, trial evaluating the efficacy of Gemcitabine and Docetaxel in patients with relapsed or refractory metastatic colorectal adenocarcinoma with methylated CHFR and/or microsatellite instability (MSI) phenotype.

Phase 2
Completed
Conditions
metastatic colorectal cancer
10017990
Registration Number
NL-OMON44946
Lead Sponsor
Vrije Universiteit Medisch Centrum
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Completed
Sex
Not specified
Target Recruitment
40
Inclusion Criteria

histologically or cytologically confirmed metastastic or unresectable colorectal adenocarcioma measurable disease
intolerant or refractory to one or more standard lines of chemotherapy
age>18
ECOG 0-1
life expectancy of greater than 12 weeks
normal organ and marrow function
MSI phenotype of archival tissue biopsy determined by PCR and IHC
CHFR gene promoter methylation in archival tissue biopsy
ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

chemotherapy or radiotherapy within 4 weeks prior to entering study, or not being recovered from adverse events.
receiving any other investigational agents
known brain metastases
history of allergic reactions attributed to cmpounds of simiar chemical or biological composition to gemcitabine or docetaxel.
receiving any medications or substances thtat are inhibitors or inducers of CYP3A4
uncontrolled intercurrent illness
pregnant women
HIV positive patients

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
<p>Primary Objectives<br /><br><br /><br>Determine the response rate of gemcitabine and docetaxel combination therapy<br /><br>for treatment of relapsed or refractory metastatic colorectal adenocarcinoma<br /><br>with methylation of CHFR and/or microsatellite instability</p><br>
Secondary Outcome Measures
NameTimeMethod
<p>Secondary Objectives<br /><br><br /><br>Determine the progression free survival with gemcitabine and docetaxel<br /><br>combination therapy in the selected patient population<br /><br>Determine the overall survival with gemcitabine and docetaxel combination<br /><br>therapy in the selected patient population<br /><br>Assess CHFR methylation in circulating tumor DNA and compare to CHFR<br /><br>methylation observed in tumor tissue<br /><br>Assess changes in CHFR methylation in circulating tumor DNA over the time of<br /><br>therapy to determine if CHFR demethylation occurs as a predictor of progression<br /><br>Analyze tumor tissue using a global methylation approach to develop a more<br /><br>robust predictive signature of treatment response<br /><br>Evaluate changes in quality of life for patients treated with this regimen by<br /><br>serial measurements using the QLQ-C30 and QLQ-CR29 questionnaire.</p><br>
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