Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Gemcitabine and Docetaxel in Patients With Relapsed or Refractory Metastatic Colorectal Adenocarcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01639131
Recruitment Status : Active, not recruiting
First Posted : July 12, 2012
Last Update Posted : April 8, 2019
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:
Determine the efficacy of combination Gemcitabine and Docetaxel chemotherapy in the treatment of metastatic colorectal cancer with CHFR and/or Microsatellite Instability (MSI) phenotype.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Adenocarcinoma Drug: Gemcitabine Drug: Docetaxel Drug: Filgrastim or Pegfilgrastim Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 10, 2012
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ARM I
Patients will receive intravenous gemcitabine 800mg/m2 on days 1 and 8 and docetaxel 70mg/m2 on day 8 of each 21 day cycle. Patients will receive filgrastim (G-CSF) on days 9 through 15 or pegfilgrastim 6mg on day 9 or 10 of each cycle.
Drug: Gemcitabine
intravenous gemcitabine 800mg/m2 on days 1 and 8

Drug: Docetaxel
docetaxel 70mg/m2 on day 8 of each 21 day cycle

Drug: Filgrastim or Pegfilgrastim
filgrastim (G-CSF) on days 9 through 15 or pegfilgrastim 6mg on day 9 or 10 of each cycle




Primary Outcome Measures :
  1. Response [ Time Frame: 4 years ]
    Determine the response rate of gemcitabine and docetaxel combination therapy for treatment of relapsed or refractory metastatic colorectal adenocarcinoma with methylation of CHFR and/or microsatellite instability


Secondary Outcome Measures :
  1. Progression free survival [ Time Frame: 4 years ]
    Determine the progression free survival with gemcitabine and docetaxel combination therapy in the selected patient population

  2. Overall survival [ Time Frame: 4 years ]
    Determine the overall survival with gemcitabine and docetaxel combination therapy in the selected patient population

  3. CHFR methylation [ Time Frame: 4 years ]
    Assess CHFR methylation in circulating tumor DNA and compare to CHFR methylation observed in tumor tissue

  4. CHFR methylation II [ Time Frame: 4 years ]
    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

  5. Global methylation [ Time Frame: 4 years ]
    Analyze tumor tissue using a global methylation approach to develop a more robust predictive signature of treatment response

  6. Change in Quality of life [ Time Frame: 4 years ]
    Evaluate change in quality of life for patients treated with this regimen by serial measurements using the QLQ-C30 and QLQ-CR29 questionnaire.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01639131


Locations
Layout table for location information
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21205
Netherlands
VU Medisch Centrum
Amsterdam, Netherlands, 1081 HV
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Investigators
Layout table for investigator information
Principal Investigator: Nilofer Azad SKCCC at JHMI

Layout table for additonal information
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT01639131     History of Changes
Other Study ID Numbers: J1214
NA_00069666 ( Other Identifier: JHMIRB )
First Posted: July 12, 2012    Key Record Dates
Last Update Posted: April 8, 2019
Last Verified: April 2019

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
Gemcitabine
Docetaxel
Filgrastim
Pegfilgrastim

Additional relevant MeSH terms:
Layout table for MeSH terms
Adenocarcinoma
Microsatellite Instability
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Genomic Instability
Pathologic Processes
Gemcitabine
Docetaxel
Lenograstim
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Adjuvants, Immunologic