Gemcitabine and Docetaxel in Patients With Relapsed or Refractory Metastatic Colorectal Adenocarcinoma
Condition: Metastatic Colorectal Adenocarcinoma
MeSH terms: Adenocarcinoma
Intervention: Gemcitabine; Docetaxel; Filgrastim or Pegfilgrastim
Intervention description: intravenous gemcitabine 800mg/m2 on days 1 and 8; intravenous docetaxel 70mg/m2 on day 8 of each 21 day cycle; filgrastim (granulocyte colony-stimulating factor [G-CSF]) on days 9 through 15 or pegfilgrastim 6 mg on day 9 or 10 of each cycle
Intervention MeSH terms: Gemcitabine; Docetaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Gemcitabine; Docetaxel; Filgrastim; Pegfilgrastim; Colorectal Adenocarcinoma

Summary:

      The primary goal of the trail was to determine the efficacy of combining Gemcitabine and
      Docetaxel in treatment of metastatic colorectal cancer with CHFR and/or Microsatellite
      Instability (MSI) phenotype.
    

Eligibility criteria:

        Inclusion:

          -  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 document.

        Exclusion Criteria:

          -  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 events.

          -  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
             C.

          -  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
             study requirements.

          -  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.