AzTrials
AzTrials

Colorectal CancerPhase 1NCT02512172

A Study of Enhancing Response to MK-3475 in Advanced Colorectal Cancer

A Phase 1 study testing Oral CC-486, Romidepsin and MK-3475 in people with Colorectal Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

Completed

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

Official record
Search all trials

Trial summary

This study is being done to test the safety and effectiveness of the combination of intravenous (IV) romidepsin and/or oral 5-azacitidine with IV MK-3475 in people with microsatellite stable (MSS) advanced colorectal cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer
What is being tested?
Oral CC-486, Romidepsin and MK-3475
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
1 siteUnited States
Study dates
19 Feb 2016to 20 Nov 2021
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Have histologically confirmed microsatellite stable metastatic colorectal cancer and have received at least one line of treatment for metastatic colorectal cancer including fluoropyrimidines, oxaliplatin and/or irinotecan
  • Be willing and able to provide written informed consent/assent for the trial
  • Be 18 years of age on day of signing informed consent
  • Have measurable disease
  • Have biopsiable disease. If biopsy is attempted and unsuccessful (the patient undergoes an invasive procedure), the patient may still be treated
  • Have a performance status of 0 or 1 on the ECOG Performance Scale at study entry
Show all 12Show fewer
  • Demonstrate adequate organ function
  • Female subject of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication
  • Female subjects of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication
  • Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
  • In patients with liver metastases, there should be <50% involvement of the liver.
  • Patients must have had < 3 prior therapies in the metastatic setting.

Who cannot join

  • Patients whose tumors have progressed at the first restaging during first line therapy
  • Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
  • Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks (6 weeks for nitrosureas or mitomycin C) prior to study Day 1 or who has not recovered from adverse events due to a previously administered agent
  • Has a known additional malignancy that is progressing or requires active treatment
Show all 19Show fewer
  • Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
  • Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Any clinical or radiological ascites or pleural effusions
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). Prior therapies with other immunomodulatory agents must be reviewed by the PI and may be cause for ineligibility
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
  • Has known active Hepatitis B or Hepatitis C
  • Has received a live vaccine within 30 days prior to the first dose of trial treatment
  • Any known cardiac abnormalities

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, 21205

Other trials in United States

About this study

Official title: A Study of Using Epigenetic Modulators to Enhance Response to MK-3475 in Microsatellite Stable Advanced Colorectal Cancer

This study is being done to test the safety and effectiveness of the combination of intravenous (IV) romidepsin and/or oral 5-azacitidine with IV MK-3475 in people with microsatellite stable (MSS) advanced colorectal cancer.

Read the detailed description

This study is being done to test the safety and effectiveness of the combination of intravenous (IV) romidepsin and/or oral CC-486 with IV MK-3475 in people with microsatellite stable advanced colorectal cancer.

People with advanced colorectal tumors that are microsatellite stable (MSS) may join this study. Tumors that are MSS positive are not deficient in repair of DNA.

This is a pilot study that will look at different ways of making MSS colorectal tumors sensitive to MK-3475 by giving 14 or 21 days of an epigenetic agent (oral CC-486 and/or romidepsin).

Participants will be randomly assigned (by chance, like drawing numbers from a hat) to one of three study drug combinations:

  1. Oral CC-486 taken daily for 21 days (and later shortened to 14 days if there are side effects) and IV MK-3475 given every 2 weeks.
  2. IV romidepsin given once weekly for 3 weeks and IV MK-3475 given every 2 weeks C. Oral CC-486 taken daily for 21 days (and later shortened to 14 days if there side effects) and IV romidepsin given every 2 weeks and IV MK-3475 given every 2 weeks.

Each arm is repeated every 28 days and will continue until the point that the study drug are no longer working. It will not be possible to cross over onto another arm if a participant's disease does not respond to the study drugs.

In this study investigators are looking for the following information:

  • What effects, good and/or bad, the combination of oral CC-486 and/or romidepsin in combination with MK-3475 has on participants' cancer; and
  • If the genetic and chemical make-up of participants' blood and tumor cells play a role in a response to oral CC-486 and/or romidepsin in combination with MK-3475.
Being tested
Oral CC-486, Romidepsin, MK-3475
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • Oral CC-486Drug

    Also called oral azacitidine, oral aza

  • RomidepsinDrug

    Also called Istodax

  • MK-3475Drug

    Also called pembrolizumab

Study groups in NCT02512172
Study groupRoleWhat they receive
Oral CC-486 & MK-3475ExperimentalOral CC-486 300 mg days 1-14 or 21 every 28 days + IV MK-3475 200 mg days 1 and 15 every 28 days
Receives: Drug: Oral CC-486; Drug: MK-3475
Romidepsin & MK-3475ExperimentalRomidepsin 14 mg/m2 days 1, 8 and 15 + IV MK-3475 200 mg days 1 and 15 every 28 days
Receives: Drug: Romidepsin; Drug: MK-3475
Oral CC-486 & Romidepsin & MK-3475ExperimentalOral CC-486 300 mg days 1-14 or 21 + romidepsin 7 mg/m2 (days 1, 8 and 15) + IV MK-3475 200 mg days 1 and 15 every 28 days.
Receives: Drug: Oral CC-486; Drug: Romidepsin; Drug: MK-3475

What is being measured

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

  1. Degree of change in tumor infiltrating lymphocytes

    Change in the number of CD8+ TILs and/or the ratio of CD8+/CD4+ TILs in tumors pre- and post- treatment.

    Measured: 1 year

  2. Number of Patients Experiencing a DLT (dose-limiting toxicity) as defined by NCI CTCAE v4.0

    Adverse events are defined by NCI CTCAE v4.0. The DLT observation period is one cycle (28 days).

    Measured: 5 years

Secondary outcomes (2)

  1. Immune-related Progression-free Survival (irPFS) at 20 weeks

    irPFS rate is defined as the percentage of patients with disease progression (irPD or relapse from irCR as assessed using irRC criteria) or death due to any cause at 20 weeks. Per irRC criteria, Complete Response (irCR) is the disappearance of all target lesions, Partial Response (irPR) is a decrease in tumor burden by 50% or greater by a consecutive assessment at least 4 weeks after first documentation, Stable Disease (irSD) is the failure to meet criteria for irCR or irPR (in absence of irPD), Progressive Disease (irPD) is at least 25% increase in tumor burden relative to nadir. Estimation based on the Kaplan-Meier curve.

    Measured: 20 weeks

  2. Overall Survival (OS)

    OS will be measured from date of first dose until death or end of followup (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.

    Measured: 4 years

Timeline

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

  1. First posted30 Jul 2015 (estimated)
  2. Study start19 Feb 2016
  3. Primary completion20 Nov 2021
  4. Study completion20 Nov 2021

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 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02512172
Sponsor's protocol ID
J1538
Other IDs
IRB00060125
Status last verified
Dec 2025
First submitted
2 Jul 2015
Last updated
3 Dec 2025
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Oral CC-486, Romidepsin and MK-3475 in people with Colorectal Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site 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 12 inclusion and 19 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 3 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Degree of change in tumor infiltrating lymphocytes (time frame: 1 year). The study lists 2 primary outcomes in all. 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 NCT02512172.

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 3 Dec 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in