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Phase 2 Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors

This study is currently recruiting participants.
Verified October 2017 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT01876511
First Posted: June 12, 2013
Last Update Posted: October 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
  Purpose
This study will be looking at whether MK-3475 (an antibody that blocks negative signals to T cells) is effective (anti-tumor activity) and safe in three different patient populations. These include: 1. patients with MSI positive colon cancer, 2. patients with MSI negative colon cancer 3. patients with other MSI positive cancers, and 4. patients with MSI negative cancer with a mutator phenotype.

Condition Intervention Phase
MSI Positive Colorectal Cancer MSI Negative Colorectal Cancer MSI Positive Non-Colorectal Cancers Drug: MK-3475 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Immune-related progression free survival (irPFS) rate at 20 weeks in patients with MSI positive and negative colorectal adenocarcinoma using immune related response criteria (irRC) [ Time Frame: 4 years ]
  • Objective response rate (irORR) at 20 weeks in patients with MSI positive and negative colorectal adenocarcinoma using immune related response criteria (irRC) [ Time Frame: 4 years ]
  • Immune-related progression free survival (irPFS) rate in patients with MSI positive non-colorectal adenocarcinoma using immune related response criteria (irRC) at 20 weeks [ Time Frame: 4 years ]
  • objective response rate in patients with MSI-negative cancer with a mutator phenotype using RECIST 1.1 criteria [ Time Frame: 4 years ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: 4 years ]
  • irPFS and PFS in patients with MSI positive and negative tumors at 28 weeks using irRC and RECIST 1.1 [ Time Frame: 4 years ]
  • Best overall response rate and disease control rate in patients with MSI positive and negative tumors [ Time Frame: 4 years ]
  • Number of participants experiencing immune-related toxicities (IRAEs) [ Time Frame: 4 years ]
  • Does MSI as a marker predict treatment response [ Time Frame: 4 years ]
  • Identify alternative markers of MSI status. This includes but is not limited to MLH 1, MSH 2, MSH 6, PMS2, BRAF pV600E, and TGFBR2. [ Time Frame: 4 years ]

Estimated Enrollment: 171
Study Start Date: September 2013
Estimated Study Completion Date: June 2021
Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MSI Positive Colorectal Cancer Drug: MK-3475
MK-3475 10 mg/kg every 14 days
Experimental: MSI Negative Colorectal Cancer Drug: MK-3475
MK-3475 10 mg/kg every 14 days
Experimental: MSI Positive Non-Colorectal Cancer Drug: MK-3475
MK-3475 10 mg/kg every 14 days
Experimental: MSI Negative with Mutator Phenotype Drug: MK-3475
MK-3475 200mg flat dose every 21 days

  Eligibility

Information from the National Library of Medicine

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

Inclusion Criteria:

1. Arm 1 only: Patients with MSI positive colorectal cancer 2. Arm 2 only: Patients with MSI negative colorectal cancer 3. Arm 3 only: Patients with MSI positive non-colorectal cancer 4. Arm 4 only: patients with hypermutated MSI negative cancer 4. Have measurable disease 5. ECOG Performance Status of 0 to 1 6. Adequate organ function as defined by study-specified laboratory tests 7. Must use acceptable form of birth control through the study and for 28 days after final dose of study drug 8. Signed informed consent form 9. Willing and able to comply with study procedures 10. Agree to have a biopsy of their cancer 11. Patients with colon cancer must have received at least two prior cancer therapy regimens.

12. Patients with other cancer types must have received at least one prior cancer therapy

Exclusion Criteria:

  1. Patients with uncontrolled intercurrent illness, including but not limited to ongoing or active infection, systematic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric condition that would limit compliance with study requirements. .
  2. Patients who have had chemotherapy or biological cancer therapy within 2 weeks prior to the first dose of study drug
  3. Patients who have had radiation within 2 weeks prior to the first dose of study drug
  4. Patients who have undergone major surgery within 4 weeks of dosing of investigational agent
  5. Patients who have received another investigational product or investigational device within 4 weeks prior to receiving study drug
  6. Patients who have received any of the following concomitant therapy: IL-2, interferon, or other non-study immunotherapy regimens, immunosuppressive agents, other investigational therapies or chronic use of systemic corticosteroids within one week prior to first dose of study drug
  7. Patients who have received a live vaccine within 4 weeks prior to or after any dose of MK-3475
  8. Patients who have received growth factors, including but not limited to granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc. within 2 weeks of study drug administration
  9. Patient who have had prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, or anti-CTLA-4 antibodies
  10. Patients with history of any autoimmune disease:inflammatory bowel disease, (including ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus (SLE) autoimmune vasculitis, CNS or motor neuropathy considered to be of autoimmune origin.
  11. Patients who have known history of infection with HIV, hepatitis B, or hepatitis C
  12. Patients with evidence of interstitial lung disease
  13. Systemically active steroid use
  14. Patients on home oxygen
  15. Patients with oxygen saturation of <92% on room air by pulse oximetry
  16. Pregnant or lactating
  17. Conditions, including alcohol or drug dependence, or intercurrent illness that would affect the patient's ability to comply with study visits and procedures
  18. Patient with known active central nervous system metastases and/or carcinomatous meningitis.
  19. Patients with primary brain tumors.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01876511


Locations
United States, California
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: George Fisher, MD       georgeaf@stanford.edu   
Principal Investigator: George Fisher, MD         
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231
Contact: Holly Kemberling, RN    443-287-5013    hkember1@jhmi.edu   
Principal Investigator: Dung Le, MD         
Investigator Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, NIH Active, not recruiting
Bethesda, Maryland, United States, 20892
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: John Hays, MD    614-293-6529    John.Hays@osumc.edu   
Principal Investigator: John Hays, MD         
United States, Oregon
Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213
Contact: Todd Crocenzi, MD       Todd.Crocenzi@providence.org   
Principal Investigator: Todd Crocenzi, MD         
United States, Pennsylvania
University of Pennsylvania, Abramson Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Kim R Binder, MD    215-360-0735    Kim.ReissBinder@uphsupenn.edu   
Principal Investigator: Kim R Binder, MD         
University of Pittsburgh Cancer Institute Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: James Lee, MD, PhD       leejj@upmc.edu   
Principal Investigator: James Lee, MD; PhD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Dung Le, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01876511     History of Changes
Other Study ID Numbers: J1365
MK-3475-016 ( Other Identifier: Merck )
NA_00085756 ( Other Identifier: JHMIRB )
First Submitted: June 10, 2013
First Posted: June 12, 2013
Last Update Posted: October 6, 2017
Last Verified: October 2017

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
MSI
MSS
MLH 1
MSH 2
MSH 6
PMS2
BRAF pV600E
TGFBR2
Mutation load
tumor mutation load
mutation burden
tumor mutation burden
hypermutation
POLE

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
Antineoplastic Agents