NCT01105377

Brief Summary

This phase II trial is studying how well giving azacitidine together with entinostat works in treating patients with metastatic colorectal cancer. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Entinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving azacitidine together with entinostat may kill more tumor cells.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
47

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Apr 2010

Typical duration for phase_2

Geographic Reach
1 country

14 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2010

Completed
14 days until next milestone

First Submitted

Initial submission to the registry

April 15, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

April 16, 2010

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2012

Completed
1.7 years until next milestone

Results Posted

Study results publicly available

November 1, 2013

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2014

Completed
Last Updated

August 1, 2014

Status Verified

July 1, 2014

Enrollment Period

1.9 years

First QC Date

April 15, 2010

Results QC Date

August 29, 2013

Last Update Submit

July 30, 2014

Conditions

Recurrent Colon CancerRecurrent Rectal CancerStage IV Colon CancerStage IV Rectal Cancer

Outcome Measures

Primary Outcomes (1)

  • Confirmed Tumor Response

    Each evaluable patient is classified as having a confirmed tumor response if they have either a complete response (CR) or partial response (PR) lasts at least 4 weeks. Tumor response is measured by using RECIST v1.1 (Response Evaluation Criteria in Solid Tumors). A CR is defined as a disappearance of all target lesions, and each target lymph node must have reduction in short axis to \<1.0 cm. A PR is defined as a 30% decrease in the sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation, compared to pre-treatment measurements. The confirmed response rate is calculated as the number of confirmed CR+PR, divided by the total number of evaluable patients, with 95% confidence intervals estimated using the approach of Duffy and Santner.

    At 6 month evaluation

Secondary Outcomes (1)

  • Time to Progression

    From the start of treatment to the earliest of the date documenting disease progression, assessed up to 3 years

Study Arms (1)

Treatment (entinostat, azacitidine)

EXPERIMENTAL

Patients receive azacitidine subcutaneously on days 1-5 and 8-10 and oral entinostat on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: entinostatDrug: azacitidineOther: laboratory biomarker analysis

Interventions

entinostatDRUG

Given orally

Also known as: HDAC inhibitor SNDX-275, SNDX-275
Treatment (entinostat, azacitidine)
azacitidineDRUG

Given SC

Also known as: 5-AC, 5-azacytidine, azacytidine, Vidaza
Treatment (entinostat, azacitidine)
laboratory biomarker analysisOTHER

Correlative studies

Treatment (entinostat, azacitidine)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically confirmed metastatic colorectal cancer
  • Measurable disease
  • Patient has failed ≥ 2 prior chemotherapy regimens
  • Not a candidate for curative resection
  • No CNS metastases within ≤ 2 years
  • Treatment for brain metastasis and whole brain disease that has remained stable for \> 3 months allowed
  • Patients who have not been treated with steroid therapy may be allowed
  • ECOG performance status 0-1
  • Life expectancy ≥ 12 weeks
  • Leukocytes ≥ 3,000/mm\^3
  • ANC ≥ 1,500/mm\^3
  • Platelet count ≥ 100,000/mm\^3
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • Creatinine normal OR creatinine clearance ≥ 60 mL/min
  • +21 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (14)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

University of Southern California/Norris Cancer Center

Los Angeles, California, 90033, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Minnesota Oncology Hematology PA-Maplewood

Maplewood, Minnesota, 55109, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Metro-Minnesota CCOP

Saint Louis Park, Minnesota, 55416, United States

Location

United Hospital

Saint Paul, Minnesota, 55102, United States

Location

Lakeview Hospital

Stillwater, Minnesota, 55082, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

  • Li H, Chiappinelli KB, Guzzetta AA, Easwaran H, Yen RW, Vatapalli R, Topper MJ, Luo J, Connolly RM, Azad NS, Stearns V, Pardoll DM, Davidson N, Jones PA, Slamon DJ, Baylin SB, Zahnow CA, Ahuja N. Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers. Oncotarget. 2014 Feb 15;5(3):587-98. doi: 10.18632/oncotarget.1782.

    PMID: 24583822DERIVED

MeSH Terms

Conditions

Colonic NeoplasmsRectal Neoplasms

Interventions

entinostatAzacitidine

Condition Hierarchy (Ancestors)

Colorectal NeoplasmsIntestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal Diseases

Intervention Hierarchy (Ancestors)

Aza CompoundsOrganic ChemicalsCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosides

Results Point of Contact

Title
Nilofer S. Azad, M.D.
Organization
Johns Hopkins Oncology Center
nazad2@jhmi.edu

Study Officials

  • Nilofer Azad

    Mayo Clinic

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

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

Study Record Dates

First Submitted

April 15, 2010

First Posted

April 16, 2010

Study Start

April 1, 2010

Primary Completion

March 1, 2012

Study Completion

May 1, 2014

Last Updated

August 1, 2014

Results First Posted

November 1, 2013

Record last verified: 2014-07

Locations

US(14)