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 Phenotype
- Patients must have histologically or cytologically confirmed metastatic or
unresectable adenocarcinoma of the colon or rectum.
- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded for
non-nodal lesions and short axis for nodal lesions) as >20 mm with conventional
techniques or as >10 mm with spiral CT scan, MRI, or calipers by clinical exam. See
Section 11 for the evaluation of measurable disease.
- Patients must be either intolerant or refractory to one or more standard line(s) of
chemotherapy treatment prior to enrollment. Toxicity from prior regimens must be
resolved to less than or equal to grade 1 prior to enrollment. Patients with grade 2
neurotoxicity may be enrolled on a case by case basis at the discretion of the
principle investigator. Patients should be off all treatment for at least 4 weeks
prior to trial enrollment.
- Age >18 years. Because no dosing or adverse event data are currently available on
the use of gemcitabine in combination with docetaxel in patients <18 years of age
with colorectal adenocarcinoma, children are excluded from this study, but will be
eligible for future pediatric trials.
- ECOG performance status 0 or 1 (Karnofsky >70%, see Appendix A).
- Life expectancy of greater than 12 weeks.
- Patients must have normal organ and marrow function.
Additional eligibility criteria:
- Microsatellite instability phenotype of archival tissue biopsy determined by treating
institution by PCR and IHC assay
- Methylation CHFR gene promoter in archival tissue biopsy
- As gemcitabine and docetaxel are known to be teratogenic, women of child-bearing
potential and men must agree to use adequate contraception (hormonal or barrier
method of birth control; abstinence) prior to study entry and for the duration of
study participation. Should a woman become pregnant or suspect she is pregnant while
she or her partner is participating in this study, she should inform her treating
physician immediately. Men treated or enrolled on this protocol must also agree to
use adequate contraception prior to the study, for the duration of study
participation, and 4 months after completion of treatment.
- Ability to understand and the willingness to sign a written informed consent
- Patients who have had chemotherapy or radiotherapy within 4 weeks prior to entering
the study or those who have not recovered from adverse events due to agents
administered more than 4 weeks earlier.
- Patients who are receiving any other investigational agents.
- Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to gemcitabine or docetaxel.
- Patients receiving any medications or substances that are inhibitors or inducers of
CYP 3A4 are ineligible. Lists including medications and substances known or with the
potential to interact with the cytochrome 450 3A4 isoenzyme are provided in appendix
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
- Pregnant women are excluded from this study because of the potential for teratogenic
or abortifacient effects of study medications. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with gemcitabine and docetaxel breastfeeding should be discontinued if the
mother is treated. These potential risks may also apply to other agents used in this
study including supportive medications.
- HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with gemcitabine and docetaxel. In
addition, these patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Appropriate studies will be undertaken in patients
receiving combination antiretroviral therapy when indicated.