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Study of Pembrolizumab in Combination With Chemotherapy for Patients With Advanced Colorectal Cancer

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: NCT02375672
Recruitment Status : Completed
First Posted : March 2, 2015
Results First Posted : October 8, 2021
Last Update Posted : February 16, 2022
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Kathy Miller, MD, Hoosier Cancer Research Network

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Colorectal Cancer
Interventions Drug: Pembrolizumab
Drug: mFOLFOX6
Enrollment 30
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Pembrolizumab (MK-3475) + mFOLFOX6
Hide Arm/Group Description

Following the safety run-in cohort:

mFOLFOX6 Treatment D1 and D15 (every 2 weeks); Pembrolizumab (MK-3475) IV over 30 minutes (every 3 weeks)

Pembrolizumab: Pembrolizumab (MK-3475) 200mg IV over 30 minutes every 3 weeks

mFOLFOX6: mFOLFOX6 Treatment D1 and D15 (Cycle = 28 days)

  • Oxaliplatin 85 mg/m^2 IV with
  • Leucovorin 400 mg/m^2 IV followed by
  • 5FU 400 mg/m^2 bolus and then 2400 mg/m^2 via continuous infusion
Period Title: Overall Study
Started 30
Completed 10
Not Completed 20
Reason Not Completed
remain on follow up             20
Arm/Group Title Pembrolizumab (MK-3475) + mFOLFOX6
Hide Arm/Group Description

Following the safety run-in cohort:

mFOLFOX6 Treatment D1 and D15 (every 2 weeks); Pembrolizumab (MK-3475) IV over 30 minutes (every 3 weeks)

Pembrolizumab: Pembrolizumab (MK-3475) 200mg IV over 30 minutes every 3 weeks

mFOLFOX6: mFOLFOX6 Treatment D1 and D15 (Cycle = 28 days)

  • Oxaliplatin 85 mg/m^2 IV with
  • Leucovorin 400 mg/m^2 IV followed by
  • 5FU 400 mg/m^2 bolus and then 2400 mg/m^2 via continuous infusion
Overall Number of Baseline Participants 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 30 participants
47.5
(28 to 74)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Female
11
  36.7%
Male
19
  63.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
29
  96.7%
Unknown or Not Reported
1
   3.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
4
  13.3%
White
26
  86.7%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 30 participants
30
ECOG Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
0
21
  70.0%
1
9
  30.0%
[1]
Measure Description: Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) from 0-5 that describes a patient's level of functioning where 0=Fully active, able to carry on all pre-disease performance without restriction and 5=Dead.
Stage at Presentation   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
I
1
   3.3%
II A
2
   6.7%
II B
0
   0.0%
III A
0
   0.0%
III B
2
   6.7%
III C
3
  10.0%
IV
22
  73.3%
[1]
Measure Description:

The TNM system helps describe cancer in great detail. But, for many cancers, the TNM combinations are grouped into five less-detailed stages.

Stage 0: Abnormal cells are present but have not spread to nearby tissue. Also called carcinoma in situ, or CIS. CIS is not cancer, but it may become cancer.

Stage I, Stage II, and Stage III: Cancer is present. The higher the number, the larger the cancer tumor and the more it has spread into nearby tissues.

Stage IV: The cancer has spread to distant parts of the body.
Sites of Metastasis  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 30 participants
Liver 22
Lung 7
Lymph Node 5
Bone 2
Ileum 3
Peritoneum 3
Other 5
1.Primary Outcome
Title Median Progression Free Survival (mPFS)
Hide Description

Determine if pembrolizumab (MK-3475) in combination with chemotherapy improves median progression free survival (mPFS) compared to historical standards.

Response Criteria - Evaluation of target lesions Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started
Time Frame From time of registration to the time of documented progression per RECIST 1.1 or subject death (estimate 14 months)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pembrolizumab (MK-3475) + mFOLFOX6
Hide Arm/Group Description:

Following the safety run-in cohort:

mFOLFOX6 Treatment D1 and D15 (every 2 weeks); Pembrolizumab (MK-3475) IV over 30 minutes (every 3 weeks)

Pembrolizumab: Pembrolizumab (MK-3475) 200mg IV over 30 minutes every 3 weeks

mFOLFOX6: mFOLFOX6 Treatment D1 and D15 (Cycle = 28 days)

  • Oxaliplatin 85 mg/m^2 IV with
  • Leucovorin 400 mg/m^2 IV followed by
  • 5FU 400 mg/m^2 bolus and then 2400 mg/m^2 via continuous infusion
Overall Number of Participants Analyzed 30
Median (80% Confidence Interval)
Unit of Measure: months
8.8
(7.7 to 11.3)
2.Secondary Outcome
Title Disease Assessment for Objective Response Rate (ORR)
Hide Description To determine the number of patients who achieve complete response and partial response per irRC criteria.
Time Frame Begin C1D1 and every 8 weeks thereafter (up to 24 months)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pembrolizumab (MK-3475) + mFOLFOX6
Hide Arm/Group Description:

Following the safety run-in cohort:

mFOLFOX6 Treatment D1 and D15 (every 2 weeks); Pembrolizumab (MK-3475) IV over 30 minutes (every 3 weeks)

Pembrolizumab: Pembrolizumab (MK-3475) 200mg IV over 30 minutes every 3 weeks

mFOLFOX6: mFOLFOX6 Treatment D1 and D15 (Cycle = 28 days)

  • Oxaliplatin 85 mg/m^2 IV with
  • Leucovorin 400 mg/m^2 IV followed by
  • 5FU 400 mg/m^2 bolus and then 2400 mg/m^2 via continuous infusion
Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
17
  56.7%
3.Secondary Outcome
Title Disease Assessment for Disease Control Rate
Hide Description Disease control rate (DCR), defined as the sum of subjects with complete response, partial response and stable disease per RECIST 1.1 criteria.
Time Frame Begin C1D1 and every 8 weeks thereafter (up to 24 months) per RECIST 1.1 criteria
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pembrolizumab (MK-3475) + mFOLFOX6
Hide Arm/Group Description:

Following the safety run-in cohort:

mFOLFOX6 Treatment D1 and D15 (every 2 weeks); Pembrolizumab (MK-3475) IV over 30 minutes (every 3 weeks)

Pembrolizumab: Pembrolizumab (MK-3475) 200mg IV over 30 minutes every 3 weeks

mFOLFOX6: mFOLFOX6 Treatment D1 and D15 (Cycle = 28 days)

  • Oxaliplatin 85 mg/m^2 IV with
  • Leucovorin 400 mg/m^2 IV followed by
  • 5FU 400 mg/m^2 bolus and then 2400 mg/m^2 via continuous infusion
Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
30
 100.0%
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description Overall Survival (OS) reported as number of subject alive at a median followup time of 19.9 months.
Time Frame Subject should be followed from time of registration till the time of subject death up to a maximum 35.5 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pembrolizumab (MK-3475) + mFOLFOX6
Hide Arm/Group Description:

Following the safety run-in cohort:

mFOLFOX6 Treatment D1 and D15 (every 2 weeks); Pembrolizumab (MK-3475) IV over 30 minutes (every 3 weeks)

Pembrolizumab: Pembrolizumab (MK-3475) 200mg IV over 30 minutes every 3 weeks

mFOLFOX6: mFOLFOX6 Treatment D1 and D15 (Cycle = 28 days)

  • Oxaliplatin 85 mg/m^2 IV with
  • Leucovorin 400 mg/m^2 IV followed by
  • 5FU 400 mg/m^2 bolus and then 2400 mg/m^2 via continuous infusion
Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
Alive
20
  66.7%
Expired
10
  33.3%
5.Secondary Outcome
Title Number of Patients With Grade 3 or Higher Treatment Related Adverse Event
Hide Description

To assess safety and tolerability of mFOLFOX6 and pembrolizumab (MK-3475) combination chemotherapy in patients with advanced colorectal cancer per CTCAE v4.0.

Events are considered related if they assessed possible, probable or definite with study drug.
Time Frame Begin C1D1 and very 2 weeks (Day 1) for up to 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Pembrolizumab (MK-3475) + mFOLFOX6
Hide Arm/Group Description:

Following the safety run-in cohort:

mFOLFOX6 Treatment D1 and D15 (every 2 weeks); Pembrolizumab (MK-3475) IV over 30 minutes (every 3 weeks)

Pembrolizumab: Pembrolizumab (MK-3475) 200mg IV over 30 minutes every 3 weeks

mFOLFOX6: mFOLFOX6 Treatment D1 and D15 (Cycle = 28 days)

  • Oxaliplatin 85 mg/m^2 IV with
  • Leucovorin 400 mg/m^2 IV followed by
  • 5FU 400 mg/m^2 bolus and then 2400 mg/m^2 via continuous infusion
Overall Number of Participants Analyzed 30
Measure Type: Count of Participants
Unit of Measure: Participants
15
  50.0%
Time Frame Adverse events (AEs) was reported from the time of consent and until 30 days after last dose of study drug up to a maximum 108 weeks.
Adverse Event Reporting Description The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) v4 were utilized for AE reporting
 
Arm/Group Title Pembrolizumab (MK-3475) + mFOLFOX6
Hide Arm/Group Description

Following the safety run-in cohort:

mFOLFOX6 Treatment D1 and D15 (every 2 weeks); Pembrolizumab (MK-3475) IV over 30 minutes (every 3 weeks)

Pembrolizumab: Pembrolizumab (MK-3475) 200mg IV over 30 minutes every 3 weeks

mFOLFOX6: mFOLFOX6 Treatment D1 and D15 (Cycle = 28 days)

  • Oxaliplatin 85 mg/m^2 IV with
  • Leucovorin 400 mg/m^2 IV followed by
  • 5FU 400 mg/m^2 bolus and then 2400 mg/m^2 via continuous infusion
All-Cause Mortality
Pembrolizumab (MK-3475) + mFOLFOX6
Affected / at Risk (%)
Total   10/30 (33.33%)    
Hide Serious Adverse Events
Pembrolizumab (MK-3475) + mFOLFOX6
Affected / at Risk (%) # Events
Total   7/30 (23.33%)    
Blood and lymphatic system disorders   
FEBRILE NEUTROPENIA * 1  3/30 (10.00%)  3
Endocrine disorders   
ENDOCRINE DISORDERS * 1  1/30 (3.33%)  1
Gastrointestinal disorders   
COLITIS * 1  1/30 (3.33%)  1
DIARRHEA * 1  1/30 (3.33%)  1
GASTROINTESTINAL DISORDERS * 1  1/30 (3.33%)  1
NAUSEA * 1  1/30 (3.33%)  1
VOMITING * 1  1/30 (3.33%)  1
General disorders   
FEVER * 1  1/30 (3.33%)  1
Immune system disorders   
ANAPHYLAXIS * 1  1/30 (3.33%)  1
Vascular disorders   
THROMBOEMBOLIC EVENT * 1  1/30 (3.33%)  2
1
Term from vocabulary, CTCAEv4
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Pembrolizumab (MK-3475) + mFOLFOX6
Affected / at Risk (%) # Events
Total   30/30 (100.00%)    
Blood and lymphatic system disorders   
ANEMIA * 1  5/30 (16.67%)  7
BLOOD AND LYMPHATIC SYSTEM DISORDERS * 1  1/30 (3.33%)  1
FEBRILE NEUTROPENIA * 1  1/30 (3.33%)  1
Endocrine disorders   
ADRENAL INSUFFICIENCY * 1  1/30 (3.33%)  1
HYPERTHYROIDISM * 1  1/30 (3.33%)  1
HYPOTHYROIDISM * 1  3/30 (10.00%)  4
Eye disorders   
CONJUNCTIVITIS * 1  1/30 (3.33%)  2
EYE DISORDERS * 1  1/30 (3.33%)  1
EYE PAIN * 1  1/30 (3.33%)  1
Gastrointestinal disorders   
ABDOMINAL PAIN * 1  10/30 (33.33%)  16
ASCITES * 1  1/30 (3.33%)  3
BLOATING * 1  2/30 (6.67%)  2
CONSTIPATION * 1  10/30 (33.33%)  15
DIARRHEA * 1  14/30 (46.67%)  31
DRY MOUTH * 1  2/30 (6.67%)  2
DYSPEPSIA * 1  5/30 (16.67%)  5
FECAL INCONTINENCE * 1  1/30 (3.33%)  2
GASTROINTESTINAL DISORDERS * 1  3/30 (10.00%)  3
HEMORRHOIDAL HEMORRHAGE * 1  1/30 (3.33%)  1
LIP PAIN * 1  1/30 (3.33%)  1
MUCOSITIS ORAL * 1  10/30 (33.33%)  15
NAUSEA * 1  22/30 (73.33%)  37
ORAL PAIN * 1  1/30 (3.33%)  1
RECTAL HEMORRHAGE * 1  5/30 (16.67%)  10
RECTAL PAIN * 1  2/30 (6.67%)  2
VOMITING * 1  9/30 (30.00%)  13
General disorders   
CHILLS * 1  4/30 (13.33%)  6
EDEMA LIMBS * 1  3/30 (10.00%)  4
FACIAL PAIN * 1  1/30 (3.33%)  1
FATIGUE * 1  18/30 (60.00%)  63
FEVER * 1  5/30 (16.67%)  8
GAIT DISTURBANCE * 1  1/30 (3.33%)  1
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS * 1  3/30 (10.00%)  3
INFUSION RELATED REACTION * 1  2/30 (6.67%)  3
PAIN * 1  1/30 (3.33%)  1
Immune system disorders   
ALLERGIC REACTION * 1  1/30 (3.33%)  1
Infections and infestations   
PAPULOPUSTULAR RASH * 1  2/30 (6.67%)  2
SINUSITIS * 1  1/30 (3.33%)  1
UPPER RESPIRATORY INFECTION * 1  2/30 (6.67%)  2
URINARY TRACT INFECTION * 1  1/30 (3.33%)  1
Investigations   
ALANINE AMINOTRANSFERASE INCREASED * 1  8/30 (26.67%)  13
ALKALINE PHOSPHATASE INCREASED * 1  5/30 (16.67%)  6
ASPARTATE AMINOTRANSFERASE INCREASED * 1  7/30 (23.33%)  12
BLOOD BILIRUBIN INCREASED * 1  6/30 (20.00%)  11
LYMPHOCYTE COUNT DECREASED * 1  3/30 (10.00%)  11
NEUTROPHIL COUNT DECREASED * 1  10/30 (33.33%)  21
PLATELET COUNT DECREASED * 1  8/30 (26.67%)  26
WEIGHT GAIN * 1  2/30 (6.67%)  2
WEIGHT LOSS * 1  5/30 (16.67%)  5
WHITE BLOOD CELL DECREASED * 1  5/30 (16.67%)  18
Metabolism and nutrition disorders   
ANOREXIA * 1  8/30 (26.67%)  16
DEHYDRATION * 1  1/30 (3.33%)  1
HYPERCALCEMIA * 1  2/30 (6.67%)  2
HYPERGLYCEMIA * 1  8/30 (26.67%)  35
HYPOALBUMINEMIA * 1  3/30 (10.00%)  4
HYPOGLYCEMIA * 1  1/30 (3.33%)  1
HYPOKALEMIA * 1  4/30 (13.33%)  4
Musculoskeletal and connective tissue disorders   
ARTHRITIS * 1  1/30 (3.33%)  1
BACK PAIN * 1  3/30 (10.00%)  4
BONE PAIN * 1  1/30 (3.33%)  1
BUTTOCK PAIN * 1  1/30 (3.33%)  1
GENERALIZED MUSCLE WEAKNESS * 1  1/30 (3.33%)  1
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDER * 1  3/30 (10.00%)  4
NECK PAIN * 1  1/30 (3.33%)  1
PAIN IN EXTREMITY * 1  2/30 (6.67%)  3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) * 1  1/30 (3.33%)  1
Nervous system disorders   
DYSESTHESIA * 1  2/30 (6.67%)  3
DYSGEUSIA * 1  6/30 (20.00%)  7
HEADACHE * 1  6/30 (20.00%)  8
NERVOUS SYSTEM DISORDERS * 1  6/30 (20.00%)  15
PARESTHESIA * 1  4/30 (13.33%)  4
PERIPHERAL MOTOR NEUROPATHY * 1  1/30 (3.33%)  1
PERIPHERAL SENSORY NEUROPATHY * 1  19/30 (63.33%)  68
SINUS PAIN * 1  1/30 (3.33%)  1
SOMNOLENCE * 1  1/30 (3.33%)  1
SYNCOPE * 1  1/30 (3.33%)  1
Psychiatric disorders   
ANXIETY * 1  2/30 (6.67%)  2
DEPRESSION * 1  3/30 (10.00%)  4
HALLUCINATIONS * 1  1/30 (3.33%)  1
INSOMNIA * 1  2/30 (6.67%)  4
Renal and urinary disorders   
HEMATURIA * 1  1/30 (3.33%)  1
RENAL AND URINARY DISORDERS * 1  1/30 (3.33%)  1
Reproductive system and breast disorders   
ERECTILE DYSFUNCTION * 1  1/30 (3.33%)  1
PELVIC PAIN * 1  1/30 (3.33%)  1
Respiratory, thoracic and mediastinal disorders   
ALLERGIC RHINITIS * 1  2/30 (6.67%)  2
COUGH * 1  3/30 (10.00%)  8
DYSPNEA * 1  3/30 (10.00%)  3
EPISTAXIS * 1  1/30 (3.33%)  1
NASAL CONGESTION * 1  1/30 (3.33%)  2
PNEUMONITIS * 1  2/30 (6.67%)  2
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS * 1  1/30 (3.33%)  1
SINUS DISORDER * 1  1/30 (3.33%)  1
SORE THROAT * 1  3/30 (10.00%)  3
Skin and subcutaneous tissue disorders   
ALOPECIA * 1  3/30 (10.00%)  3
DRY SKIN * 1  2/30 (6.67%)  2
HYPERHIDROSIS * 1  1/30 (3.33%)  1
PRURITUS * 1  3/30 (10.00%)  4
RASH ACNEIFORM * 1  4/30 (13.33%)  4
RASH MACULO-PAPULAR * 1  4/30 (13.33%)  4
SKIN AND SUBCUTANEOUS TISSUE DISORDERS * 1  3/30 (10.00%)  3
SKIN HYPERPIGMENTATION * 1  1/30 (3.33%)  1
Vascular disorders   
HYPERTENSION * 1  3/30 (10.00%)  4
HYPOTENSION * 1  1/30 (3.33%)  1
1
Term from vocabulary, CTCAEv4
*
Indicates events were collected by non-systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Fauzia Sharmin
Organization: Hoosier Cancer Research Network
Phone: (317) 634-5842 ext 75
EMail: fsharmin@hoosiercancer.org
Layout table for additonal information
Responsible Party: Kathy Miller, MD, Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT02375672    
Other Study ID Numbers: HCRN GI14-186
First Submitted: February 24, 2015
First Posted: March 2, 2015
Results First Submitted: July 29, 2021
Results First Posted: October 8, 2021
Last Update Posted: February 16, 2022