Pembrolizumab for the Treatment of Recurrent High Grade Neuroendocrine Carcinoma (Pembro NEC)

• ClinicalTrials.gov Identifier: NCT03190213
• Recruitment Status: Terminated
• First Posted: June 16, 2017
• Results First Posted: January 27, 2020
• Last Update Posted: June 22, 2021
• Sponsor: University of Utah
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): University of Utah

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Neuroendocrine Tumors
• Intervention: Drug: Pembrolizumab Injection
• Enrollment: 6

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Pembrolizumab: All Patients
Arm/Group Description	Pembrolizumab 200 mg will be administered as an IV infusion every 3 weeks.
Period Title: Overall Study
Started	6
Completed	6
Not Completed	0

Baseline Characteristics

Arm/Group Title		Pembrolizumab: All Patients
Arm/Group Description		Pembrolizumab 200 mg will be administered as an IV infusion every 3 weeks.
Overall Number of Baseline Participants		6
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	5 83.3%
	>=65 years	1 16.7%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	6 participants
		49.17 (17.03)
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	6 participants
		44; (34 to 78)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants
	Female	5 83.3%
	Male	1 16.7%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 participants
	Hispanic or Latino	1 16.7%
	Not Hispanic or Latino	5 83.3%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	6 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	0 0.0%
	White	5 83.3%
	More than one race	0 0.0%
	Unknown or Not Reported	1 16.7%

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate
Description	Overall response was measured using Immune Related Response Evaluation Criteria in Solid Tumors (irRECIST). At baseline, lesions found on CT or MRI imaging are cataloged as "target" or "non-target" lesions, and the longest dimensions of target lesions (or shortest dimension of target lymph nodes) are summed. irRECIST defines Complete Response (irCR) as a complete disappearance of all lesions after baseline. Partial Response (irPR) is defined as a 30% or more decrease in the target lesion measurements. Overall response rate is defined the percentage of participants with a best response of irCR + irPR.
Time Frame	planned for up to two years from baseline; actual time was up to 230 days (average of 70.5 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pembrolizumab: All Patients
Arm/Group Description:	Pembrolizumab 200 mg will be administered as an IV infusion every 3 weeks.
Overall Number of Participants Analyzed	6
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	0; (0 to 45.9)

2. Secondary Outcome

Title	Clinical Benefit Rate
Description	Clinical benefit was measured using irRECIST. At baseline, lesions found on CT or MRI imaging are cataloged as "target" or "non-target" lesions, and the longest dimensions of target lesions (or shortest dimension of target lymph nodes) are summed. irRECIST defines irCR as a complete disappearance of all lesions after baseline. irPR is defined as a 30% or more decrease in the target lesion measurements. Progressive Disease (irPD) is a defined as a 20% or more increase in target lesion measurements. Stable Disease (irSD) is neither a sufficient shrinkage to qualify as irPR or irCR nor an increase that would qualify as irPD. Clinical Benefit Rate is defined as the percentage of participants with a best response of irCR + irPR + irSD.
Time Frame	planned for up to two years from baseline; actual time was up to 230 days (average of 70.5 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pembrolizumab: All Patients
Arm/Group Description:	Pembrolizumab 200 mg will be administered as an IV infusion every 3 weeks.
Overall Number of Participants Analyzed	6
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	16.7; (0.4 to 64.1)

3. Secondary Outcome

Title	Median Progression Free Survival
Description	Progression free survival (PFS) is the length of time during and after treatment that a participant lives and the disease does not get worse. PFS was measured as the time from first dose of pembrolizumab until disease progression by irRECIST criteria (>= 20% increase in target lesion measurements), and is reported as the median number of days patients survived without disease progression as calculated by the Kaplan-Meier method.
Time Frame	planned for up to four years from baseline; actual time was up to 230 days (average of 70.5 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pembrolizumab: All Patients
Arm/Group Description:	Pembrolizumab 200 mg will be administered as an IV infusion every 3 weeks.
Overall Number of Participants Analyzed	6
Median (95% Confidence Interval); Unit of Measure: days
	42.5 [1]; (40 to NA)

[1]

Value is infinity because there were too few patients to get a number.

4. Secondary Outcome

Title	Median Overall Survival
Description	Overall survival (OS) is the length of time from the start of treatment that a participant lives. OS was measured as the time from first dose of pembrolizumab until the death of the participant or the end of follow-up (whichever was first), and is reported as the median number of days patients survived as calculated by the Kaplan-Meier method. This study was intended to follow participants up to four years after the initiation of study treatment, but the study and the follow-up period were terminated prematurely. The maximum follow up was 360 days.
Time Frame	planned for up to four years from baseline; actual time was up to 230 days (average of 70.5 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pembrolizumab: All Patients
Arm/Group Description:	Pembrolizumab 200 mg will be administered as an IV infusion every 3 weeks.
Overall Number of Participants Analyzed	6
Median (95% Confidence Interval); Unit of Measure: days
	262 [1]; (108 to NA)

[1]

Value is infinity because there were too few patients to get a number.

5. Secondary Outcome

Title	Number of Patients With Adverse Events Reported
Description	Adverse Events were reported using the Common Terminology Criteria for Adverse Events (CTCAE) version 4. Each adverse event reported is assigned a severity grade from 1 to 5, where 1 is mild, 2 is moderate, 3 is severe, 4 is life threatening, and 5 indicates the event resulted in death. The number of patients experiencing any Grade 1-2 event and the number of patients experiencing any Grade 3 event are reported. There were no Grade 4 or Grade 5 events reported on this study. AEs were reported during study treatment and up to 90 days after last dose of treatment.
Time Frame	planned for up to two years of treatment plus 90 days; actual time was up to 338 days (average of 170 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Pembrolizumab: All Patients
Arm/Group Description:	Pembrolizumab 200 mg will be administered as an IV infusion every 3 weeks.
Overall Number of Participants Analyzed	6
Measure Type: Count of Participants; Unit of Measure: Participants
Grade 1-2 Event	5 83.3%
Grade 3 Event	5 83.3%

Adverse Events

Time Frame	from the first dose of pembrolizumab until 30 days (for other adverse events) or 90 days (for serious adverse events) after last dose of pembrolizumab (average duration of 170 days, max duration of 338 days)
Adverse Event Reporting Description	The occurrence of adverse events was sought by non-directive questioning of the patient at each visit or phone contact during the study. Adverse events were also detected when they were volunteered by the patient during or between visits or through physical examination, laboratory test, or other assessments.
Arm/Group Title	Pembrolizumab: All Patients
Arm/Group Description	Pembrolizumab 200 mg will be administered as an IV infusion every 3 weeks.
All-Cause Mortality
	Pembrolizumab: All Patients
	Affected / at Risk (%)
Total	2/6 (33.33%)
Serious Adverse Events
	Pembrolizumab: All Patients
	Affected / at Risk (%)	# Events
Total	4/6 (66.67%)
Gastrointestinal disorders
Abdominal pain † 1	2/6 (33.33%)
Vomiting † 1	1/6 (16.67%)
Metabolism and nutrition disorders
Dehydration † 1	1/6 (16.67%)
Hyponatremia † 1	1/6 (16.67%)
1 Term from vocabulary, CTCAE (4.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Pembrolizumab: All Patients
	Affected / at Risk (%)	# Events
Total	6/6 (100.00%)
Blood and lymphatic system disorders
Lymph node pain † 1	1/6 (16.67%)
Gastrointestinal disorders
Abdominal pain † 1	3/6 (50.00%)
Anal pain † 1	1/6 (16.67%)	2
Constipation † 1	2/6 (33.33%)
Diarrhea † 1	3/6 (50.00%)	5
Dyspepsia † 1	1/6 (16.67%)
Nausea † 1	4/6 (66.67%)
Rectal pain † 1	1/6 (16.67%)
Small intestinal obstruction † 1	1/6 (16.67%)	2
Vomiting † 1	1/6 (16.67%)
General disorders
Edema limbs † 1	2/6 (33.33%)
Fatigue † 1	3/6 (50.00%)	4
Infusion related reaction † 1	1/6 (16.67%)
Pain † 1	1/6 (16.67%)
Immune system disorders
Allergic reaction † 1	1/6 (16.67%)
Autoimmune disorder † 1	1/6 (16.67%)
Infections and infestations
Infections and infestations - Other: Thrush † 1	1/6 (16.67%)
Urinary tract infection † 1	1/6 (16.67%)
Investigations
Lymphocyte count decreased † 1	1/6 (16.67%)
Metabolism and nutrition disorders
Anorexia † 1	2/6 (33.33%)	3
Dehydration † 1	1/6 (16.67%)
Hyperglycemia † 1	1/6 (16.67%)	2
Nervous system disorders
Headache † 1	1/6 (16.67%)
Nervous system disorders - Other: Allodynia † 1	1/6 (16.67%)	2
Seizure † 1	1/6 (16.67%)	2
Spasticity † 1	1/6 (16.67%)
Psychiatric disorders
Insomnia † 1	1/6 (16.67%)	2
Restlessness † 1	1/6 (16.67%)
Reproductive system and breast disorders
Pelvic pain † 1	1/6 (16.67%)
Respiratory, thoracic and mediastinal disorders
Dyspnea † 1	1/6 (16.67%)	2
Hypoxia † 1	1/6 (16.67%)
Skin and subcutaneous tissue disorders
Pruritus † 1	1/6 (16.67%)
Vascular disorders
Hot flashes † 1	1/6 (16.67%)
1 Term from vocabulary, CTCAE (4.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Data Manager
• Organization: Huntsman Cancer Institute Research Compliance Office
• Phone: 8015850601
• EMail: compliance@hci.utah.edu

• Responsible Party: University of Utah
• ClinicalTrials.gov Identifier: NCT03190213
• Other Study ID Numbers: HCI102310
• First Submitted: June 13, 2017
• First Posted: June 16, 2017
• Results First Submitted: December 10, 2019
• Results First Posted: January 27, 2020
• Last Update Posted: June 22, 2021