Clinical trial NCT03736720: Liposomal Irinotecan, Fluorouracil and Leucovorin in Treating Patients With Refractory Advanced High Grade Neuroendocrine Cancer of Gastrointestinal, Unknown, or Pancreatic Origin
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Locally Advanced Digestive System Neuroendocrine Carcinoma
Locally Advanced Pancreatic Neuroendocrine Carcinoma
Metastatic Digestive System Neuroendocrine Carcinoma
Metastatic Pancreatic Neuroendocrine Carcinoma
Refractory Digestive System Neuroendocrine Carcinoma
Refractory Pancreatic Neuroendocrine Carcinoma
Unresectable Digestive System Neuroendocrine Carcinoma
Unresectable Pancreatic Neuroendocrine Carcinoma
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
Collaborators: name: Ipsen
First posted: 2018-11-09
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: PRIMARY OBJECTIVES:

I. To determine the objective response rate liposomal irinotecan (nanoliposomal irinotecan \[Nal-IRI\]) + fluorouracil (5FU) and leucovorin in patients with refractory advanced high grade neuroendocrine cancer of gastrointestinal (GI), unknown or pancreatic origin.

SECONDARY OBJECTIVES:

I. To determine overall survival, progression-free survival, time to treatment failure, safety, clinical response and, quality of life (QOL) changes resulting from the combination treatment of nanoliposomal irinotecan (Nal-IRI) + fluorouracil (5FU) and leucovorin.

EXPLORATORY OBJECTIVES:

I. Genetic profiling for mutations will be conducted on all pre-study tumor samples and compared to changes in immune response.

OUTLINE:

Patients receive liposomal irinotecan intravenously (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.

After completion of study treatment, patients are followed up for 30 days, then every 2 months thereafter.

Eligibility criteria: Inclusion Criteria:

* 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).
  * Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception or to abstain from sexual intercourse for the duration of their participation in the study.
* Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
timeFrame: Within 6 months of treatment initiation
Secondary outcomes:
measure: Overall Survival
timeFrame: From first dosing of study treatment combination to time of death or imitation of a new therapy, assessed up to 3 years
measure: Progression-free Survival Assessed by RECIST 1.1
timeFrame: From first dosing of study treatment combination to disease progression, assessed up to 3 years
measure: Time-to Treatment Failure
timeFrame: From enrollment to discontinuation of treatment, assessed up to 3 years
measure: Proportion of Patients Achieving an Objective Response Based on Prior Response to Platinum Etoposide
timeFrame: Up to 3 years
measure: Clinical Benefit Response
timeFrame: Up to 3 years
measure: Quality of Life (QOL) as Assessed by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30)
timeFrame: From treatment initiation until treatment completion/progression (up to 3 years).
measure: Incidence of Grade 3+ Treatment Related Adverse Events (TRAE)
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Stony Brook
country: United States
facility: Stony Brook Cancer Center
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: Renuka Iyer
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.