Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors (Cohorts A, B and C)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01876511
Recruitment Status : Completed
First Posted : June 12, 2013
Results First Posted : January 7, 2020
Last Update Posted : February 6, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information
First Submitted Date  ICMJE June 10, 2013
First Posted Date  ICMJE June 12, 2013
Results First Submitted Date  ICMJE November 6, 2019
Results First Posted Date  ICMJE January 7, 2020
Last Update Posted Date February 6, 2020
Actual Study Start Date  ICMJE September 2013
Actual Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 20, 2019)
  • Immune-related Progression Free Survival (irPFS) at 20 Weeks in MSI Positive and Negative Colorectal Adenocarcinoma Participants Using Immune Related Response Criteria (irRC) During Stages 1 and 2 [ Time Frame: 20 weeks ]
    For Cohorts A and B: 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.
  • Immune-related Objective Response Rate in MSI Positive and Negative Colorectal Adenocarcinoma Participants Using Immune Related Response Criteria (irRC) During Stages 1 and 2 [ Time Frame: 28 months ]
    For Cohorts A and B: Immune-related Objective Response Rate (irORR) is defined as the percentage of patients achieving a complete response (irCR) or partial response (irPR) based on irRC criteria. 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.
  • Immune-related Progression Free Survival (irPFS) at 20 Weeks in MSI Positive Non-colorectal Adenocarcinoma Participants Using Immune Related Response Criteria (irRC) During Stages 1 and 2 [ Time Frame: 20 weeks ]
    For Cohort C: 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.
  • Objective Response Rate in MSI Positive Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [ Time Frame: 28 months ]
    For Cohorts A and C: Objective Response Rate (ORR) is defined as the percentage of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions.
  • Progression Free Survival (PFS) at 20 Weeks in MSI Positive Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [ Time Frame: 20 weeks ]
    For Cohorts A and C: PFS is defined as the percentage of patients with disease progression (PD or relapse from CR as assessed using RECIST 1.1 criteria) or death due to any cause at 20 weeks. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.
Original Primary Outcome Measures  ICMJE
 (submitted: June 10, 2013)
  • 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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2019)
  • Overall Survival (OS) [ Time Frame: 4 years ]
    OS will be measured from date of first dose until death or end of follow-up (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.
  • Immune-related Progression Free Survival (irPFS) at 28 Weeks in MSI Positive and Negative Solid Tumor Malignancies Using Immune Related Response Criteria (irRC) [ Time Frame: 28 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 28 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.
  • Objective Response Rate (ORR) in MSI Positive and Negative Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [ Time Frame: 28 months ]
    ORR is defined as the percentage of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions.
  • Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity [ Time Frame: 28 months ]
    When calculating the incidence of AEs, each adverse event (AE) (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.
  • Progression Free Survival (PFS) at 28 Weeks in MSI Positive and Negative Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [ Time Frame: 28 weeks ]
    PFS is defined as the percentage of patients with disease progression (PD or relapse from CR as assessed using RECIST 1.1 criteria) or death due to any cause at 28 weeks. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.
  • Disease Control Rate in MSI Positive and Negative Solid Tumor Malignancies Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [ Time Frame: 28 months ]
    Disease Control Rate (DCR) is defined as the percentage of patients achieving a complete response (CR) or partial response (PR) or stable disease (SD) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.
  • Does MSI as a Marker Predict Treatment Response [ Time Frame: 28 months ]
    ORR was used to determine whether MSI is a marker that predicts treatment response. This is the same data presented in outcome measure number 8 (ORR, to test against null of 5%).
Original Secondary Outcome Measures  ICMJE
 (submitted: June 10, 2013)
  • 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: Continuous ]
  • Does MSI as a Marker Predict Treatment Response [ Time Frame: 4 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors (Cohorts A, B and C)
Official Title  ICMJE Phase 2 Study of MK-3475 in Patients With Microsatellite Unstable (MSI) Tumors
Brief Summary 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 and 3. patients with other MSI positive cancers.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • MSI Positive Colorectal Cancer
  • MSI Negative Colorectal Cancer
  • MSI Positive Non-Colorectal Cancers
Intervention  ICMJE Drug: MK-3475
MK-3475 10 mg/kg every 14 days
Study Arms  ICMJE
  • Experimental: Cohort A: MSI Positive Colorectal Cancer
    Intervention: Drug: MK-3475
  • Experimental: Cohort B: MSI Negative Colorectal Cancer
    Intervention: Drug: MK-3475
  • Experimental: Cohort C: MSI Positive Non-Colorectal Cancer
    Intervention: Drug: MK-3475
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 20, 2019)
113
Original Estimated Enrollment  ICMJE
 (submitted: June 10, 2013)
71
Actual Study Completion Date  ICMJE August 2019
Actual Primary Completion Date August 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Cohort A only: Patients with microsatellite instability (MSI) positive colorectal cancer
  • Cohort B only: Patients with MSI negative colorectal cancer
  • Cohort C only: Patients with MSI positive non-colorectal cancer -
  • Have measurable disease
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
  • Adequate organ function as defined by study-specified laboratory tests
  • Must use acceptable form of birth control through the study and for 28 days after final dose of study drug
  • Signed informed consent form
  • Willing and able to comply with study procedures
  • Agree to have a biopsy of participants' cancer
  • Patients with colon cancer must have received at least two prior cancer therapy regimens.
  • Patients with other cancer types must have received at least one prior cancer therapy
  • Progressive disease

Exclusion Criteria:

  • 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.
  • Patients who have had chemotherapy or biological cancer therapy within 2 weeks prior to the first dose of study drug
  • Patients who have had radiation within 2 weeks prior to the first dose of study drug
  • Patients who have undergone major surgery within 4 weeks of dosing of investigational agent
  • Patients who have received another investigational product or investigational device within 4 weeks prior to receiving study drug
  • Patients who have received any of the following concomitant therapy: Interleukin-2 (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
  • Patients who have received a live vaccine within 4 weeks prior to or after any dose of MK-3475 (exception: inactivated flu vaccines)
  • 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
  • Patient who have had prior treatment with anti-PD-1 (anti-programmed cell death protein 1), anti-PD-L1, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, or anti-CTLA-4 antibodies
  • 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, central nervous system (CNS) or motor neuropathy considered to be of autoimmune origin.
  • Patients who have known history of infection with HIV, hepatitis B, or hepatitis C
  • Patients with evidence of interstitial lung disease
  • Systemically active steroid use
  • Patients on home oxygen
  • Patients with oxygen saturation of <92% on room air by pulse oximetry
  • Pregnant or lactating
  • Conditions, including alcohol or drug dependence, or intercurrent illness that would affect the patient's ability to comply with study visits and procedures
  • Patient with known active central nervous system metastases and/or carcinomatous meningitis.
  • Patients with primary brain tumors.
  • Requires any other form of systemic or localized antineoplastic therapy while on study
  • Has any tissue or organ allograft
  • Patients with history of allogeneic hematopoeitic stem cell transplant
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01876511
Other Study ID Numbers  ICMJE J1365 (Cohort A, B and C)
MK-3475-016 ( Other Identifier: Merck )
NA_00085756 ( Other Identifier: JHMIRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Principal Investigator: Dung Le, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP