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Gemcitabine Hydrochloride and Docetaxel in Treating Patients with Relapsed or Refractory Colorectal Cancer That Is Metastatic or Cannot Be Removed by Surgery

Trial Status: Closed to Accrual and Intervention

This phase II trial studies how well gemcitabine hydrochloride and docetaxel work in treating patients with colorectal cancer that has returned or did not respond to treatment and has spread to other parts of the body or cannot be removed by surgery. Drugs used in chemotherapy, such as gemcitabine hydrochloride and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

Inclusion Criteria

  • 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 computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
  • 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 principal investigator; patients should be off all treatment for at least 4 weeks prior to trial enrollment
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky >= 70%)
  • Life expectancy of greater than 12 weeks
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal or 5 X ULN in the presence of liver metastases
  • Creatinine within normal institutional limits or creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Microsatellite instability (MSI) phenotype of archival tissue biopsy determined by treating institution by polymerase chain reaction (PCR) and immunohistochemistry (IHC) assay
  • Methylation CHFR gene promoter in archival tissue biopsy * A patient will be considered to have CHFR methylation if he/she has a methylation specific band on methylation-specific PCR (MSP) for the CHFR gene or lack of expression by IHCs; MSP primers are publicly reported and developed at Oncomethylome in a Clinical Laboratory Improvement Amendments (CLIA) laboratory; patients who test positive for MSI at any of the 5 loci will be considered MSI+ as per standard convention or who have absent expression of mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MSH6), or PMS2 postmeiotic segregation increased 2 (PMS2) by IHC * Results from another institution’s CLIA-certified MSI/IHC will be considered for eligibility * Patients with microsatellite instability and a family history supportive for a possible diagnosis of hereditary nonpolyposis colorectal cancer will be referred to a genetics counselor for further evaluation and recommendations
  • 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 3 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
  • 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 cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) are ineligible; investigator can change to a similar agent that is a non-CYP3A4 inhibitor/inducer with a washout period of 1 week
  • 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; breastfeeding should be discontinued if the mother is treated
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible


Johns Hopkins University / Sidney Kimmel Cancer Center
Contact: Nilofer Saba Azad
Phone: 410-614-9169
National Institutes of Health Clinical Center
Contact: Tim F. Greten
Phone: 301-451-4723


VU University Medical Center
Contact: Henk Verhuel
Phone: 20-444-4321


I. Determine the response rate of gemcitabine (gemcitabine hydrochloride) and docetaxel combination therapy for treatment of relapsed or refractory metastatic colorectal adenocarcinoma with methylation of checkpoint with forkhead and ring finger domain (CHFR) and/or microsatellite instability.


I. Determine the progression free survival with gemcitabine and docetaxel combination therapy in the selected patient population.

II. Determine the overall survival with gemcitabine and docetaxel combination therapy in the selected patient population.

III. Assess CHFR methylation in circulating tumor deoxyribonucleic acid (DNA) and compare to CHFR methylation observed in tumor tissue.

IV. Assess changes in CHFR methylation in circulating tumor DNA over the time of therapy to determine if CHFR demethylation occurs as a predictor of progression.

V. Analyze tumor tissue using a global methylation approach to develop a more robust predictive signature of treatment response.

VI. Evaluate changes in quality of life for patients treated with this regimen by serial measurements using the Quality of Life Questionnaire (QLQ)-Core 30 (C30) and QLQ-Colorectal (CR)29 questionnaire.


Patients receive gemcitabine hydrochloride intravenously (IV) over 30-60 minutes on days 1 and 8 and docetaxel IV over 1 hour on day 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks and then every 3 months thereafter.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Johns Hopkins University / Sidney Kimmel Cancer Center

Principal Investigator
Nilofer Saba Azad

  • Primary ID J1214
  • Secondary IDs NCI-2012-01337, NCI-2013-01567, CIR00009096, NA_00069666
  • ID NCT01639131