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

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2017 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Celgene Corporation
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT02512172
First received: July 2, 2015
Last updated: June 22, 2017
Last verified: June 2017
  Purpose
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.

Condition Intervention Phase
Colorectal Cancer Drug: Oral CC - 486 Drug: Romidepsin Drug: MK - 3475 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: A Study of Using Epigenetic Modulators to Enhance Response to MK-3475 in Microsatellite Stable Advanced Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Degree of change in tumor infiltrating lymphocytes [ Time Frame: 1 year ]
    Change is determined by the number of CD45NO+ cells per high powered field


Estimated Enrollment: 30
Study Start Date: June 2015
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oral CC - 486 & MK-3475
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
Other Names:
  • oral azacitidine
  • oral aza
Drug: MK - 3475
Other Name: pembrolizumab
Experimental: Romidepsin & MK-3475
Romidepsin 14 mg/m2 days 1, 8 and 15 + IV MK-3475 200 mg days 1 and 15 every 28 days
Drug: Romidepsin
Other Name: Istodax
Drug: MK - 3475
Other Name: pembrolizumab
Experimental: Oral CC - 486 & Romidepsin & MK-3475
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
Other Names:
  • oral azacitidine
  • oral aza
Drug: Romidepsin
Other Name: Istodax
Drug: MK - 3475
Other Name: pembrolizumab

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.

The use of CC - 486 in this research study is investigational. The word "investigational" means that the oral form of CC - 486 is not approved for marketing by the U.S. Food and Drug Administration (FDA). Oral CC - 486 has only been given to a very small number of people so far, and this combination has never before been given together to people.

Romidepsin has been approved by the FDA for the treatment of cutaneous T-cell lymphoma (blood cancer). It is not approved by the FDA for use in other cancers.

MK-3475 is an antibody. Antibodies are proteins that the immune system uses to fight infection. Researchers have designed MK-3475 to block PD-1. PD-1 is a molecule that can shut down an immune response to infection or a cancer cell. An antibody to PD-1 can stop it from turning off an immune response and may be able to boost the immune system against the 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:

A. 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.

B. 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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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
  2. Be willing and able to provide written informed consent/assent for the trial
  3. Be 18 years of age on day of signing informed consent
  4. Have measurable disease
  5. Have biopsiable disease. If biopsy is attempted and unsuccessful (the patient undergoes an invasive procedure), the patient may still be treated
  6. Have a performance status of 0 or 1 on the ECOG Performance Scale at study entry
  7. Demonstrate adequate organ function
  8. 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
  9. 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
  10. 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
  11. In patients with liver metastases, there should be <50% involvement of the liver with no tumors greater than 5 cm in size
  12. Patients must have had < 3 prior therapies in the metastatic setting.

Exclusion Criteria:

  1. Patients whose tumors have progressed at the first restaging during first line therapy
  2. 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
  3. 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
  4. 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
  5. 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
  6. Has a known additional malignancy that is progressing or requires active treatment
  7. Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
  8. 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.
  9. Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
  10. Has an active infection requiring systemic therapy.
  11. Any clinical or radiological ascites or pleural effusions
  12. 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
  13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  14. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial
  15. 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
  16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
  17. Has known active Hepatitis B or Hepatitis C
  18. Has received a live vaccine within 30 days prior to the first dose of trial treatment
  19. Any known cardiac abnormalities
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02512172

Contacts
Contact: Rosalind Walker, RN 410-955-9628 rwalker3@jhmi.edu
Contact: Amber-Lynn Mitcheltree, BA 410-502-5327 amiche13@jhmi.edu

Locations
United States, Maryland
Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21205
Principal Investigator: Nilofer Azad, MD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Merck Sharp & Dohme Corp.
Celgene Corporation
Investigators
Principal Investigator: Nilofer Azad, MD Johns Hopkins University
  More Information

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT02512172     History of Changes
Other Study ID Numbers: J1538
IRB00060125 ( Other Identifier: JHMIRB )
Study First Received: July 2, 2015
Last Updated: June 22, 2017

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Pembrolizumab
Romidepsin
Antineoplastic Agents
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on July 24, 2017