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AzTrials

Recurrent Colon CancerPhase 2NCT01105377

Azacitidine and Entinostat in Treating Patients With Metastatic Colorectal Cancer

A Phase 2 study testing entinostat, azacitidine and laboratory biomarker analysis in people with Recurrent Colon Cancer and Recurrent Rectal Cancer, run by National Cancer Institute (NCI) at 14 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
entinostat, azacitidine and laboratory biomarker analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
14 sitesUnited States
Study dates
Apr 2010to May 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 36Show fewer
  • 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
  • Negative pregnancy test
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Sensory neuropathy ≤ grade 2 allowed
  • Willing to provide tissue and blood samples
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat, azacitidine, mannitol, or other agents used in the study
  • No uncontrolled intercurrent illness including, but not limited to, any of the following:
  • Ongoing or active infection
  • NYHA class II-IV symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness and/or social situations that would limit compliance with study requirements
  • No history of severe bleeding without thrombocytopenia
  • No concurrent radiotherapy including palliative treatment
  • Toxicities from prior therapy have resolved to ≤ grade 1
  • More than 4 weeks since prior chemotherapy (> 6 weeks for nitrosoureas or mitomycin C)
  • More than 4 weeks since prior major surgical procedure
  • No prior histone deacetylase inhibitors (including valproic acid) or demethylating agents
  • No concurrent investigational agents
  • No concurrent combination antiretroviral therapy in HIV-positive patients
  • No concurrent investigational or commercial anticancer agents or therapies

Who cannot join

None listed.

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites

  • Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, 21287

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • University of Southern California/Norris Cancer Center

    Los Angeles, California, 90033

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Minnesota Oncology Hematology PA-Maplewood

    Maplewood, Minnesota, 55109

  • University of Pittsburgh Cancer Institute

    Pittsburgh, Pennsylvania, 15232

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15232

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Metro-Minnesota CCOP

    Saint Louis Park, Minnesota, 55416

  • United Hospital

    Saint Paul, Minnesota, 55102

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Lakeview Hospital

    Stillwater, Minnesota, 55082

Other trials in United States

About this study

Official title: Phase II Study of Azacitadine and Entinostat in Patients With Metastatic Colorectal Cancer

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the preliminary efficacy via Response Evaluation Criteria In Solid Tumors (RECIST) response rate of the combination of azacitidine and entinostat in patients with metastatic colorectal cancer.

SECONDARY OBJECTIVES:

  1. Explore the effects of azacitidine and entinostat on time to progression in patients with metastatic colorectal cancer.

II. To assess the toxicity for combination azacitidine and entinostat therapy.

TERTIARY OBJECTIVES:

  1. Evaluate changes in promoter methylation of selected genes from DNA in circulating serum samples.

II. To determine changes in histone deacetylase activity and acetylation of H3 and H4 histones in pre- and post-treatment tumor biopsies.

III. To evaluate correlations between these molecular effects and clinical outcomes (response, time to progression).

IV. To correlate response rates by RECIST criteria versus response rates determined be EASL (change in tumor enhancement).

OUTLINE: This is a multicenter study.

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.

Blood and tumor tissue samples are collected at baseline and periodically during courses 1-3 for DNA methylation, histone deacetylation activity, and acetylation of H3 and H4 histones analysis by PCR, western blot, and RT-PCR assays. Pharmacogenomic studies may also be conducted.

After completion of study therapy, patients are followed up every 3-6 months for up to 3 years.

Being tested
entinostat, azacitidine, laboratory biomarker analysis
Medical subject headings
Colonic Neoplasms, Rectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • entinostatDrug

    Also called HDAC inhibitor SNDX-275, SNDX-275

    Given orally

  • azacitidineDrug

    Also called 5-AC, 5-azacytidine, azacytidine, Vidaza

    Given SC

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01105377
Study groupRoleWhat they receive
Treatment (entinostat, azacitidine)ExperimentalPatients 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.
Receives: Drug: entinostat; Drug: azacitidine; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: At 6 month evaluation

Secondary outcomes (1)

  1. Time to Progression

    Time to disease progression (TTP) is defined as the time from the start of treatment to the earliest of the date documenting disease progression or most recent assessment for patients having no progression. The distribution of TTP is estimated using the method of Kaplan-Meier.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Apr 2010 (estimated)
  2. Study startApr 2010
  3. Primary completionMar 2012
  4. Study completionMay 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
47 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01105377
Sponsor's protocol ID
NCI-2010-02024
Other IDs
NCI-2010-02024, CDR0000670136, MC084B, 8341, N01CM00099, P30CA015083, N01CM00038
Status last verified
Jul 2014
First submitted
15 Apr 2010
Last updated
1 Aug 2014

Publications

  • 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.

    PubMed 24583822

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing entinostat, azacitidine and laboratory biomarker analysis in people with Recurrent Colon Cancer and Recurrent Rectal Cancer, run by National Cancer Institute (NCI) at 14 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 36 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Confirmed Tumor Response (time frame: At 6 month evaluation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01105377, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2014.

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