Study Stopped
low accrual
Liposomal Irinotecan, Fluorouracil and Leucovorin in Treating Patients With Refractory Advanced High Grade Neuroendocrine Cancer of Gastrointestinal, Unknown, or Pancreatic Origin
Phase 2 Single-Arm Study of Nanoliposomal Irinotecan With Fluorouracil and Leucovorin in Refractory Advanced High Grade Neuroendocrine Cancer of GI, Unknown or Pancreatic Origin
2 other identifiers
interventional
11
1 country
2
Brief Summary
This phase II trial studies how well liposomal irinotecan, leucovorin, and fluorouracil work in treating patients with high grade neuroendocrine cancer of gastrointestinal, unknown, or pancreatic origin that does not respond to treatment and has spread to other places in the body. Lliposomal irinotecan may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving liposomal irinotecan, leucovorin and fluorouracil may work better in treating patients with neuroendocrine cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Jun 2019
Longer than P75 for phase_2
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 5, 2018
CompletedFirst Posted
Study publicly available on registry
November 9, 2018
CompletedStudy Start
First participant enrolled
June 17, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 18, 2022
CompletedResults Posted
Study results publicly available
December 19, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
August 26, 2024
CompletedJanuary 30, 2025
January 1, 2025
3.3 years
November 5, 2018
October 16, 2023
January 16, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
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.
Within 6 months of treatment initiation
Secondary Outcomes (7)
Overall Survival
From first dosing of study treatment combination to time of death or imitation of a new therapy, assessed up to 3 years
Progression-free Survival Assessed by RECIST 1.1
From first dosing of study treatment combination to disease progression, assessed up to 3 years
Time-to Treatment Failure
From enrollment to discontinuation of treatment, assessed up to 3 years
Proportion of Patients Achieving an Objective Response Based on Prior Response to Platinum Etoposide
Up to 3 years
Clinical Benefit Response
Up to 3 years
- +2 more secondary outcomes
Study Arms (1)
Treatment (liposomal irinotecan, leucovorin, fluorouracil)
EXPERIMENTALPatients 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.
Interventions
Given IV
Given IV
Given IV
Correlative studies
Eligibility Criteria
You may qualify if:
- Participant must have a locally advanced and unresectable or metastatic gastroenteropancreatic neuroendocrine carcinoma of the gastrointestinal (GI) tract, pancreas, or of other known or unknown primary site where 5FU based therapy would be considered reasonable by the treated MD, lung primary is excluded. Patients may have either progressed on therapy or within 6 months of completing therapy, or be intolerant of therapy to be considered eligible.
- Participant must have tissue available for central pathology review and, must have pathologically/histologically confirmed high grade neuro endocrine defined as Ki-67 proliferative index of 20-100% or, must have evidence of at least 10 mitotic figures per 10 high powered fields.
- Comprehensive Genomic Profiling will be performed on archival tissue available prior to enrollment. If no archival tissue is available, then patient must have fresh biopsy prior to treatment administration if clinically indicated.
- Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 - 2.
- Leukocytes \>= 3,000/mm\^3 .
- Absolute neutrophil count \>= 1,500/mm\^3.
- Hemoglobin \>= 9 g/dL.
- Platelets \>= 100,000/mm\^3.
- Total bilirubin =\< institutional upper limit of normal (ULN) or =\< 1.5 x institutional ULN (if the patient has liver metastases.
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN or (=\< 5 x institutional ULN if the patient has liver metastases).
- Serum creatinine =\< 1.5 x institutional ULN or measured or calculated creatinine clearance by Cockcroft Gault Equation \>= 50ml/min for subjects with creatinine levels \> 1.5 x ULN.
- Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present.
- Participant must have a life expectancy of \>= 12 weeks as determined clinically by the treating physician.
- Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
- +2 more criteria
You may not qualify if:
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
- Participants with known dihydropyrimidine dehydrogenase (DPD) deficiency.
- Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
- Known hypersensitivity to any of the components of Nal-IRI, other liposomal products, fluoropyrimidines or leucovorin.
- Investigational therapy administered within 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to the first scheduled day of dosing in this study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant or nursing female participants.
- Unwilling or unable to follow protocol requirements.
- Any condition which in the Investigator?s opinion deems the participant an unsuitable candidate to receive study drug.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Roswell Park Cancer Institutelead
- Ipsencollaborator
Study Sites (2)
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Stony Brook Cancer Center
Stony Brook, New York, 11794, United States
Related Publications (1)
Abstracts Presented at the 13th Annual Multidisciplinary Neuroendocrine Tumor Medical Virtual Symposium of the North American Neuroendocrine Tumor Society, October 2-3, 2020. Pancreas. 2021 Mar 1;50(3):441-467. doi: 10.1097/MPA.0000000000001763. No abstract available.
PMID: 33835977DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Kris Attwood
- Organization
- Roswell Park Comprehensive Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Renuka Iyer
Roswell Park Cancer Institute
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 5, 2018
First Posted
November 9, 2018
Study Start
June 17, 2019
Primary Completion
October 18, 2022
Study Completion
August 26, 2024
Last Updated
January 30, 2025
Results First Posted
December 19, 2023
Record last verified: 2025-01