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

NCT01639131 | Terminated Phase 2 Results

• 2 other identifiers: J1214NA_00069666
• Study Type: interventional
• Target: 6
• Locations: 2 countries
• Sites: 3

Brief 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.

Conditions

Metastatic Colorectal Adenocarcinoma

Keywords

Gemcitabine; Docetaxel; Filgrastim; Pegfilgrastim; Colorectal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Response Rate

  The Response Rate is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.

  9 months

Secondary Outcomes (2)

• Progression-free Survival (PFS)

  9 months

• Overall Survival With Gemcitabine and Docetaxel Combination Therapy

  62 months

Study Arms (1)

Gemcitabine and Docetaxel

EXPERIMENTAL

Patients were treated with gemcitabine 800 mg/m2 on days 1 and 8 and docetaxel 70 mg/m2 on day 8 of each 21-day cycle. Patients received filgrastim (granulocyte colony-stimulating factor \[G-CSF\]) on days 9 through 15 or pegfilgrastim 6 mg on day 9 or 10 of each cycle. Patients were treated until disease progression or unacceptable adverse events (AEs), or withdrawn of the consent.

Drug: Gemcitabine; Drug: Docetaxel; Drug: Filgrastim or Pegfilgrastim

Interventions

Gemcitabine DRUG

intravenous gemcitabine 800mg/m2 on days 1 and 8

Gemcitabine and Docetaxel

Docetaxel DRUG

intravenous docetaxel 70mg/m2 on day 8 of each 21 day cycle

Gemcitabine and Docetaxel

Filgrastim or Pegfilgrastim DRUG

filgrastim (granulocyte colony-stimulating factor \[G-CSF\]) on days 9 through 15 or pegfilgrastim 6 mg on day 9 or 10 of each cycle

Gemcitabine and Docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (3)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21205, United States

Location

Center for Cancer Research, NCI

Bethesda, Maryland, 20892, United States

Location

VU Medisch Centrum

Amsterdam, 1081 HV, Netherlands

Location

Related Publications (1)

• Baretti M, Karunasena E, Zahurak M, Walker R, Zhao Y, Pisanic TR 2nd, Wang TH, Greten TF, Duffy AG, Gootjes E, Meijer G, Verheul HMW, Ahuja N, Herman JG, Azad NS. A phase 2 trial of gemcitabine and docetaxel in patients with metastatic colorectal adenocarcinoma with methylated checkpoint with forkhead and ring finger domain promoter and/or microsatellite instability phenotype. Clin Transl Sci. 2021 May;14(3):954-963. doi: 10.1111/cts.12960. Epub 2021 Apr 3.

  PMID: 33811727 DERIVED

Related Links

• A phase 2 trial of gemcitabine and docetaxel in patients with metastatic colorectal adenocarcinoma with methylated checkpoint with forkhead and ring finger domain promoter and/or microsatellite instability phenotype Marina Baretti 1, Enusha Karunasena 1,

MeSH Terms

Interventions

Gemcitabine; Docetaxel; Filgrastim; pegfilgrastim

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Nilofer Azad, MD
• Organization: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University

nazad2@jhmi.edu

410-614-9169

Study Officials

• Nilofer Azad

  SKCCC at JHMI

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2012
• First Posted: July 12, 2012
• Study Start: September 10, 2012
• Primary Completion: October 3, 2016
• Study Completion: March 11, 2019
• Last Updated: August 10, 2022
• Results First Posted: August 10, 2022

Record last verified: 2022-08

Locations

US (2); NL (1)