Trial Outcomes & Findings for Nivolumab (Anti-PD1), Tadalafil and Oral Vancomycin in People With Refractory Primary Hepatocellular Carcinoma or Liver Dominant Metastatic Cancer From Colorectal or Pancreatic Cancers (NCT NCT03785210)

Last Updated: 2023-07-11

Results Overview

Best overall response is defined as the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started) assessed by the Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progressions). Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

22 participants

Primary outcome timeframe

Every 2 months and then every 6 months after discontinuation of treatment, for survival purposes, up to 3 years

Results posted on

2023-07-11

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort 1, Arm 1, Treatment Assignment Code 1, Participants With Hepatocellular Carcinoma Participants with hepatocellular carcinoma highly suggestive of a diagnosis of hepatocellular carcinoma. Nivolumab 480 mg intravenously every 4 weeks; Tadalafil 10mg by mouth (PO) daily, and oral vancomycin 125mg every 6 hours by mouth (PO) from week 1 to week 3, week 4 off, 500 mg total daily.	Cohort 2, Arm 1, Treatment Assignment Code 1, Participants With Liver Metastases Participants with liver metastases from colorectal cancer or pancreatic ductal adenocarcinoma (PDAC). Nivolumab 480 mg intravenously every 4 weeks; Tadalafil 10mg by mouth (PO) daily, and oral vancomycin 125mg every 6 hours by mouth (PO) from week 1 to week 3, week 4 off, 500 mg total daily.
Overall Study STARTED	6	16
Overall Study COMPLETED	5	10
Overall Study NOT COMPLETED	1	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1, Arm 1, Treatment Assignment Code 1, Participants With Hepatocellular Carcinoma Participants with hepatocellular carcinoma highly suggestive of a diagnosis of hepatocellular carcinoma. Nivolumab 480 mg intravenously every 4 weeks; Tadalafil 10mg by mouth (PO) daily, and oral vancomycin 125mg every 6 hours by mouth (PO) from week 1 to week 3, week 4 off, 500 mg total daily.	Cohort 2, Arm 1, Treatment Assignment Code 1, Participants With Liver Metastases Participants with liver metastases from colorectal cancer or pancreatic ductal adenocarcinoma (PDAC). Nivolumab 480 mg intravenously every 4 weeks; Tadalafil 10mg by mouth (PO) daily, and oral vancomycin 125mg every 6 hours by mouth (PO) from week 1 to week 3, week 4 off, 500 mg total daily.
Overall Study Principal investigator decision - clinical progression	1	6

Baseline Characteristics

Nivolumab (Anti-PD1), Tadalafil and Oral Vancomycin in People With Refractory Primary Hepatocellular Carcinoma or Liver Dominant Metastatic Cancer From Colorectal or Pancreatic Cancers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1, Arm 1, Treatment Assignment Code 1, Participants With Hepatocellular Carcinoma n=6 Participants Participants with hepatocellular carcinoma highly suggestive of a diagnosis of hepatocellular carcinoma. Nivolumab 480 mg intravenously every 4 weeks; Tadalafil 10mg by mouth (PO) daily, and oral vancomycin 125mg every 6 hours by mouth (PO) from week 1 to week 3, week 4 off, 500 mg total daily.	Cohort 2, Arm 1, Treatment Assignment Code 1, Participants With Liver Metastases n=16 Participants Participants with liver metastases from colorectal cancer or pancreatic ductal adenocarcinoma (PDAC). Nivolumab 480 mg intravenously every 4 weeks; Tadalafil 10mg by mouth (PO) daily, and oral vancomycin 125mg every 6 hours by mouth (PO) from week 1 to week 3, week 4 off, 500 mg total daily.	Total n=22 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	11 Participants n=7 Participants	12 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Age, Continuous	69.08 years STANDARD_DEVIATION 8.15 • n=5 Participants	63.61 years STANDARD_DEVIATION 11.52 • n=7 Participants	65.1 years STANDARD_DEVIATION 10.81 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	11 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	16 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	10 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants	16 participants n=7 Participants	22 participants n=5 Participants

PRIMARY outcome

Timeframe: Every 2 months and then every 6 months after discontinuation of treatment, for survival purposes, up to 3 years

Outcome measures

Outcome measures
Measure	Cohort 2, Arm 1, Treatment Assignment Code 1, Participants With Liver Metastases n=16 Participants Participants with liver metastases from colorectal cancer or pancreatic ductal adenocarcinoma (PDAC). Nivolumab 480 mg intravenously every 4 weeks; Tadalafil 10mg by mouth (PO) daily, and oral vancomycin 125mg every 6 hours by mouth (PO) from week 1 to week 3, week 4 off, 500 mg total daily.	Cohort 1, Arm 1, Treatment Assignment Code 1, Participants With Hepatocellular Carcinoma n=6 Participants Participants with hepatocellular carcinoma highly suggestive of a diagnosis of hepatocellular carcinoma. Nivolumab 480 mg intravenously every 4 weeks; Tadalafil 10mg by mouth (PO) daily, and oral vancomycin 125mg every 6 hours by mouth (PO) from week 1 to week 3, week 4 off, 500 mg total daily.
Best Overall Response (BOR) Complete Response	0 Participants	0 Participants
Best Overall Response (BOR) Partial Response	0 Participants	0 Participants
Best Overall Response (BOR) Stable Disease	1 Participants	1 Participants
Best Overall Response (BOR) Progressive Disease	9 Participants	4 Participants
Best Overall Response (BOR) Not Evaluable	6 Participants	1 Participants

SECONDARY outcome

Timeframe: From first study treatment, approximately 90 days

Adverse events were assessed by the by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Cohort 2, Arm 1, Treatment Assignment Code 1, Participants With Liver Metastases n=16 Participants Participants with liver metastases from colorectal cancer or pancreatic ductal adenocarcinoma (PDAC). Nivolumab 480 mg intravenously every 4 weeks; Tadalafil 10mg by mouth (PO) daily, and oral vancomycin 125mg every 6 hours by mouth (PO) from week 1 to week 3, week 4 off, 500 mg total daily.	Cohort 1, Arm 1, Treatment Assignment Code 1, Participants With Hepatocellular Carcinoma n=6 Participants Participants with hepatocellular carcinoma highly suggestive of a diagnosis of hepatocellular carcinoma. Nivolumab 480 mg intravenously every 4 weeks; Tadalafil 10mg by mouth (PO) daily, and oral vancomycin 125mg every 6 hours by mouth (PO) from week 1 to week 3, week 4 off, 500 mg total daily.
Serious Adverse Events Possibly, Probably, and/or Definitely Related to Treatment	0 adverse events	0 adverse events

SECONDARY outcome

Timeframe: Participants were followed from the on-study date to post discontinuation of treatment until the day of death, an average of 8 months.

Overall survival is calculated from the on-study date to the day of death using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Cohort 2, Arm 1, Treatment Assignment Code 1, Participants With Liver Metastases n=16 Participants Participants with liver metastases from colorectal cancer or pancreatic ductal adenocarcinoma (PDAC). Nivolumab 480 mg intravenously every 4 weeks; Tadalafil 10mg by mouth (PO) daily, and oral vancomycin 125mg every 6 hours by mouth (PO) from week 1 to week 3, week 4 off, 500 mg total daily.	Cohort 1, Arm 1, Treatment Assignment Code 1, Participants With Hepatocellular Carcinoma n=6 Participants Participants with hepatocellular carcinoma highly suggestive of a diagnosis of hepatocellular carcinoma. Nivolumab 480 mg intravenously every 4 weeks; Tadalafil 10mg by mouth (PO) daily, and oral vancomycin 125mg every 6 hours by mouth (PO) from week 1 to week 3, week 4 off, 500 mg total daily.
Overall Survival (OS) of Nivolumab Combined With Oral Vancomycin and Tadalafil in Participants With Refractory Hepatocellular Carcinoma (HCC) or Liver Dominant Metastatic Cancer From Colorectal Cancer or Pancreatic Ductal Adenocarcinoma (PDAC)	3.4 Months Interval 2.6 to 8.7	9.4 Months Interval 2.4 to 18.3

OTHER_PRE_SPECIFIED outcome

Timeframe: Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively.

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	Cohort 2, Arm 1, Treatment Assignment Code 1, Participants With Liver Metastases n=16 Participants Participants with liver metastases from colorectal cancer or pancreatic ductal adenocarcinoma (PDAC). Nivolumab 480 mg intravenously every 4 weeks; Tadalafil 10mg by mouth (PO) daily, and oral vancomycin 125mg every 6 hours by mouth (PO) from week 1 to week 3, week 4 off, 500 mg total daily.	Cohort 1, Arm 1, Treatment Assignment Code 1, Participants With Hepatocellular Carcinoma n=6 Participants Participants with hepatocellular carcinoma highly suggestive of a diagnosis of hepatocellular carcinoma. Nivolumab 480 mg intravenously every 4 weeks; Tadalafil 10mg by mouth (PO) daily, and oral vancomycin 125mg every 6 hours by mouth (PO) from week 1 to week 3, week 4 off, 500 mg total daily.
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)	16 Participants	6 Participants

Adverse Events

Cohort 1, Arm 1, Treatment Assignment Code 1, Participants With Hepatocellular Carcinoma

Serious events: 2 serious events

Other events: 6 other events

Deaths: 5 deaths

Cohort 2, Arm 1, Treatment Assignment Code 1, Participants With Liver Metastases

Serious events: 7 serious events

Other events: 16 other events

Deaths: 15 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Tim F. Greten

National Cancer Institute

Phone: 240-760-6114

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort 1, Arm 1, Treatment Assignment Code 1, Participants With Hepatocellular Carcinoma n=6 participants at risk Participants with hepatocellular carcinoma highly suggestive of a diagnosis of hepatocellular carcinoma. Nivolumab 480 mg intravenously every 4 weeks; Tadalafil 10mg by mouth (PO) daily, and oral vancomycin 125mg every 6 hours by mouth (PO) from week 1 to week 3, week 4 off, 500 mg total daily.	Cohort 2, Arm 1, Treatment Assignment Code 1, Participants With Liver Metastases n=16 participants at risk Participants with liver metastases from colorectal cancer or pancreatic ductal adenocarcinoma (PDAC). Nivolumab 480 mg intravenously every 4 weeks; Tadalafil 10mg by mouth (PO) daily, and oral vancomycin 125mg every 6 hours by mouth (PO) from week 1 to week 3, week 4 off, 500 mg total daily.
Gastrointestinal disorders Abdominal pain	0.00% 0/6 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.	12.5% 2/16 • Number of events 2 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.
Gastrointestinal disorders Ascites	0.00% 0/6 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.	12.5% 2/16 • Number of events 2 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/6 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.
Investigations Blood bilirubin increased	0.00% 0/6 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.
Gastrointestinal disorders Colonic perforation	0.00% 0/6 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.
Gastrointestinal disorders Diarrhea	0.00% 0/6 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.
General disorders Disease progression	0.00% 0/6 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.
Gastrointestinal disorders Duodenal obstruction	0.00% 0/6 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.	6.2% 1/16 • Number of events 2 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/6 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.
General disorders Fever	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.
Vascular disorders Hematoma	0.00% 0/6 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/6 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/6 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/6 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/6 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.
Cardiac disorders Sinus tachycardia	0.00% 0/6 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.
Vascular disorders Thromboembolic event	16.7% 1/6 • Number of events 1 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.	12.5% 2/16 • Number of events 2 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.
Renal and urinary disorders Urinary retention	0.00% 0/6 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.	6.2% 1/16 • Number of events 1 • Date treatment consent signed to date off study, approximately 41 months/11 days and 36 months/22 days for the first and second group respectively. No deaths were related to research.