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

NCT02512172 | Completed Phase 1 DMC

• 2 other identifiers: J1538IRB00060125
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  1 year

• 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).

  5 years

Secondary Outcomes (2)

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

  20 weeks

• Overall Survival (OS)

  4 years

Study Arms (3)

Oral CC-486 & MK-3475

EXPERIMENTAL

Oral CC-486 300 mg days 1-14 or 21 every 28 days + IV MK-3475 200 mg days 1 and 15 every 28 days

Drug: Oral CC-486; Drug: MK-3475

Romidepsin & MK-3475

EXPERIMENTAL

Romidepsin 14 mg/m2 days 1, 8 and 15 + IV MK-3475 200 mg days 1 and 15 every 28 days

Drug: Romidepsin; Drug: MK-3475

Oral CC-486 & Romidepsin & MK-3475

EXPERIMENTAL

Oral 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.

Drug: Oral CC-486; Drug: Romidepsin; Drug: MK-3475

Interventions

MK-3475 DRUG

Also known as: pembrolizumab

Oral CC-486 & MK-3475; Oral CC-486 & Romidepsin & MK-3475; Romidepsin & MK-3475

Oral CC-486 DRUG

Also known as: oral azacitidine, oral aza

Oral CC-486 & MK-3475; Oral CC-486 & Romidepsin & MK-3475

Romidepsin DRUG

Also known as: Istodax

Oral CC-486 & Romidepsin & MK-3475; Romidepsin & MK-3475

Eligibility Criteria

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

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Merck Sharp & Dohme LLC: collaborator
• Celgene Corporation: collaborator

Study Sites (1)

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21205, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

cc-486; Azacitidine; romidepsin; pembrolizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Nilofer Azad, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2015
• First Posted: July 30, 2015
• Study Start: February 19, 2016
• Primary Completion: November 20, 2021
• Study Completion: November 20, 2021
• Last Updated: December 3, 2025

Record last verified: 2025-12

Locations

US (1)