Trial Outcomes & Findings for Liposomal Irinotecan, Fluorouracil and Leucovorin in Treating Patients With Refractory Advanced High Grade Neuroendocrine Cancer of Gastrointestinal, Unknown, or Pancreatic Origin (NCT NCT03736720)

Last Updated: 2025-01-30

Results Overview

Will be summarized using frequencies and relative frequencies; with the ORR (= CR+PR / N) estimated using an 80% confidence interval obtained using Jeffrey's prior method. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

11 participants

Primary outcome timeframe

Within 6 months of treatment initiation

Results posted on

2025-01-30

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) Patients receive liposomal irinotecan IV over 90 minutes, leucovorin IV over 30 minutes, and fluorouracil IV over 46 hours on days 1 and 15. Courses repeat every 28 days for in the absence of disease progression or unacceptable toxicity. Fluorouracil: Given IV Leucovorin: Given IV Liposomal Irinotecan: Given IV Quality-of-Life Assessment: Correlative studies
Overall Study STARTED	11
Overall Study COMPLETED	11
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Liposomal Irinotecan, Fluorouracil and Leucovorin in Treating Patients With Refractory Advanced High Grade Neuroendocrine Cancer of Gastrointestinal, Unknown, or Pancreatic Origin

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) n=11 Participants Patients receive liposomal irinotecan IV over 90 minutes, leucovorin IV over 30 minutes, and fluorouracil IV over 46 hours on days 1 and 15. Courses repeat every 28 days for in the absence of disease progression or unacceptable toxicity. Fluorouracil: Given IV Leucovorin: Given IV Liposomal Irinotecan: Given IV Quality-of-Life Assessment: Correlative studies
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants
Age, Continuous	66.0 years STANDARD_DEVIATION 10.7 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	11 participants n=5 Participants
Number of Prior Chemotherapy Regimens No Prior Regimens	0 Participants n=5 Participants
Number of Prior Chemotherapy Regimens 1 Prior Regimen	7 Participants n=5 Participants
Number of Prior Chemotherapy Regimens 2 Prior Regimens	3 Participants n=5 Participants
Number of Prior Chemotherapy Regimens Not Reported	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Within 6 months of treatment initiation

Population: 2 patients were not evaluable for response.

Outcome measures

Outcome measures
Measure	Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) n=9 Participants Patients receive liposomal irinotecan IV over 90 minutes, leucovorin IV over 30 minutes, and fluorouracil IV over 46 hours on days 1 and 15. Courses repeat every 28 days for in the absence of disease progression or unacceptable toxicity. Fluorouracil: Given IV Leucovorin: Given IV Liposomal Irinotecan: Given IV Quality-of-Life Assessment: Correlative studies
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Objective Response (CR+PR)	1 Participants
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 No Objective Response (SD+PD)	8 Participants

SECONDARY outcome

Timeframe: From first dosing of study treatment combination to time of death or imitation of a new therapy, assessed up to 3 years

Will be summarized using standard Kaplan-Meier methods; where estimates of the median time will be obtained with 95% confidence intervals.

Outcome measures

Outcome measures
Measure	Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) n=11 Participants Patients receive liposomal irinotecan IV over 90 minutes, leucovorin IV over 30 minutes, and fluorouracil IV over 46 hours on days 1 and 15. Courses repeat every 28 days for in the absence of disease progression or unacceptable toxicity. Fluorouracil: Given IV Leucovorin: Given IV Liposomal Irinotecan: Given IV Quality-of-Life Assessment: Correlative studies
Overall Survival	8.3 months Interval 2.3 to 18.2

SECONDARY outcome

Timeframe: From first dosing of study treatment combination to disease progression, assessed up to 3 years

Will be summarized using standard Kaplan-Meier methods; where estimates of the median time will be obtained with 95% confidence intervals. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) n=11 Participants Patients receive liposomal irinotecan IV over 90 minutes, leucovorin IV over 30 minutes, and fluorouracil IV over 46 hours on days 1 and 15. Courses repeat every 28 days for in the absence of disease progression or unacceptable toxicity. Fluorouracil: Given IV Leucovorin: Given IV Liposomal Irinotecan: Given IV Quality-of-Life Assessment: Correlative studies
Progression-free Survival Assessed by RECIST 1.1	3.9 months Interval 0.5 to 5.1

SECONDARY outcome

Timeframe: From enrollment to discontinuation of treatment, assessed up to 3 years

Will be summarized using standard Kaplan-Meier methods; where estimates of the median time will be obtained with 90% confidence intervals.

Outcome measures

Outcome measures
Measure	Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) n=11 Participants Patients receive liposomal irinotecan IV over 90 minutes, leucovorin IV over 30 minutes, and fluorouracil IV over 46 hours on days 1 and 15. Courses repeat every 28 days for in the absence of disease progression or unacceptable toxicity. Fluorouracil: Given IV Leucovorin: Given IV Liposomal Irinotecan: Given IV Quality-of-Life Assessment: Correlative studies
Time-to Treatment Failure	3.9 months Interval 1.7 to 4.4

SECONDARY outcome

Timeframe: Up to 3 years

Population: Only 4 patients received prior platinum etoposide.

The objective response rate (ORR) is as described in the primary analysis. Here it is reported in the subset of patients that received prior platinum etoposide therapy.

Outcome measures

Outcome measures
Measure	Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) n=4 Participants Patients receive liposomal irinotecan IV over 90 minutes, leucovorin IV over 30 minutes, and fluorouracil IV over 46 hours on days 1 and 15. Courses repeat every 28 days for in the absence of disease progression or unacceptable toxicity. Fluorouracil: Given IV Leucovorin: Given IV Liposomal Irinotecan: Given IV Quality-of-Life Assessment: Correlative studies
Proportion of Patients Achieving an Objective Response Based on Prior Response to Platinum Etoposide No Objective Response	3 Participants
Proportion of Patients Achieving an Objective Response Based on Prior Response to Platinum Etoposide Objective Response	1 Participants

SECONDARY outcome

Timeframe: Up to 3 years

Population: The appropriate data to identify patient clinical benefit status (as defined above) was not adequately obtained (no available data) and analysis can not be conducted for this outcome measure.

Defined as either achievement of pronounced and sustained (\>=4 weeks contiguous) improvement in pain intensity, analgesic consumption, or performance status, or a combination of these, without any worsening in any of the other factors, or stability in pain intensity, analgesic consumption, and performance status with pronounced and sustained (\>= 4 weeks contiguous) weight gain. Will be treated as binary data and summarized using frequencies and relative frequencies. The clinical benefit response rate will be estimated using a 90% confidence interval obtained by Jeffrey?s prior method.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From treatment initiation until treatment completion/progression (up to 3 years).

Population: There are 11 patients that have QoL data at baseline (pre-treatment). There are only 8 patients with end of treatment QoL assessment.

Will be treated as quantitative data and summarized by time-point using the mean and standard deviation. The QOL scores at each follow-up time may be compared with base-line levels using the paired t-test or sign test. The overall QoL rating ranges from 0 (poor) to 10 (good).

Outcome measures

Outcome measures
Measure	Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) n=11 Participants Patients receive liposomal irinotecan IV over 90 minutes, leucovorin IV over 30 minutes, and fluorouracil IV over 46 hours on days 1 and 15. Courses repeat every 28 days for in the absence of disease progression or unacceptable toxicity. Fluorouracil: Given IV Leucovorin: Given IV Liposomal Irinotecan: Given IV Quality-of-Life Assessment: Correlative studies
Quality of Life (QOL) as Assessed by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) Pre Treatment QoL	5.9 units on a scale Standard Deviation 1.4
Quality of Life (QOL) as Assessed by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) End of Treatment QoL	5.5 units on a scale Standard Deviation 1.7

SECONDARY outcome

Timeframe: Up to 3 years

Toxicities and adverse events will be summarized by attribution and grade using frequencies and relative frequencies. High grade (3+) toxicity and adverse event rates may be estimated using 90% confidence intervals obtained by Jeffrey's prior method. Data Safety Monitoring Board (DSMB) monitoring will also occur periodically to ensure safety of study subjects.

Outcome measures

Outcome measures
Measure	Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) n=11 Participants Patients receive liposomal irinotecan IV over 90 minutes, leucovorin IV over 30 minutes, and fluorouracil IV over 46 hours on days 1 and 15. Courses repeat every 28 days for in the absence of disease progression or unacceptable toxicity. Fluorouracil: Given IV Leucovorin: Given IV Liposomal Irinotecan: Given IV Quality-of-Life Assessment: Correlative studies
Incidence of Grade 3+ Treatment Related Adverse Events (TRAE) No Grade 3+ TRAE	4 Participants
Incidence of Grade 3+ Treatment Related Adverse Events (TRAE) Grade 3+ TRAE	7 Participants

Adverse Events

Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil)

Serious events: 6 serious events

Other events: 11 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) n=11 participants at risk Patients receive liposomal irinotecan IV over 90 minutes, leucovorin IV over 30 minutes, and fluorouracil IV over 46 hours on days 1 and 15. Courses repeat every 28 days for in the absence of disease progression or unacceptable toxicity. Fluorouracil: Given IV Leucovorin: Given IV Liposomal Irinotecan: Given IV Quality-of-Life Assessment: Correlative studies
Gastrointestinal disorders Diarrhea	9.1% 1/11 • Number of events 1 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Gastrointestinal disorders Small intestinal obstruction	9.1% 1/11 • Number of events 1 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Gastrointestinal disorders Vomiting	9.1% 1/11 • Number of events 1 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Hepatobiliary disorders Other	9.1% 1/11 • Number of events 1 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Infections and infestations Sepsis	18.2% 2/11 • Number of events 2 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Investigations Blood bilirubin increased	9.1% 1/11 • Number of events 1 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Vascular disorders Hypotension	9.1% 1/11 • Number of events 1 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Vascular disorders Superior vena cava syndrome	9.1% 1/11 • Number of events 1 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.

Other adverse events

Other adverse events
Measure	Treatment (Liposomal Irinotecan, Leucovorin, Fluorouracil) n=11 participants at risk Patients receive liposomal irinotecan IV over 90 minutes, leucovorin IV over 30 minutes, and fluorouracil IV over 46 hours on days 1 and 15. Courses repeat every 28 days for in the absence of disease progression or unacceptable toxicity. Fluorouracil: Given IV Leucovorin: Given IV Liposomal Irinotecan: Given IV Quality-of-Life Assessment: Correlative studies
Blood and lymphatic system disorders Anemia	9.1% 1/11 • Number of events 1 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Gastrointestinal disorders Abdominal pain	9.1% 1/11 • Number of events 1 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Gastrointestinal disorders Constipation	18.2% 2/11 • Number of events 2 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Gastrointestinal disorders Diarrhea	45.5% 5/11 • Number of events 5 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Gastrointestinal disorders Gastrointestinal pain	9.1% 1/11 • Number of events 1 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Gastrointestinal disorders Nausea	45.5% 5/11 • Number of events 5 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Gastrointestinal disorders Small intestinal obstruction	9.1% 1/11 • Number of events 1 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Gastrointestinal disorders Vomiting	45.5% 5/11 • Number of events 5 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
General disorders Fatigue	45.5% 5/11 • Number of events 5 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Infections and infestations Sepsis	18.2% 2/11 • Number of events 2 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Investigations Blood bilirubin increased	9.1% 1/11 • Number of events 1 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Investigations CD4 lymphocytes decreased	9.1% 1/11 • Number of events 1 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Investigations Neutrophil count decreased	27.3% 3/11 • Number of events 3 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Metabolism and nutrition disorders Hypokalemia	9.1% 1/11 • Number of events 1 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Metabolism and nutrition disorders Metabolism and nutrition disorders **Any AE - Maximum Grade Seen Hypokalemia Hypomagnesemia	9.1% 1/11 • Number of events 1 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Nervous system disorders Dysgeusia	18.2% 2/11 • Number of events 2 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Vascular disorders Hypotension	18.2% 2/11 • Number of events 2 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.
Vascular disorders Superior vena cava syndrome	9.1% 1/11 • Number of events 1 • Adverse events were followed for up to 3 years following treatment initiation, with a median time of 182 days.

Additional Information

Kris Attwood

Roswell Park Comprehensive Cancer Center

Phone: 716-845-1300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place