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FOLFIRINOX in Metastatic High Grade Gastroenteropancreatic Neuroendocrine Carcinomas

Primary Purpose

Gastro-enteropancreatic Neuroendocrine Tumor, Pancreatic Cancer, Neuroendocrine Carcinomas of Pancreas

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
FOLFIRINOX
Granulocyte colony-stimulating factor (G-CSF)
Sponsored by
H. Lee Moffitt Cancer Center and Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastro-enteropancreatic Neuroendocrine Tumor focused on measuring Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs), Metastatic, High grade, Pancreas, Neuroendocrine carcinoma of gastrointestinal tract

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically or cytologically confirmed neuroendocrine carcinoma of the gastrointestinal (GI) tract. Potential participants with unknown origin for the neuroendocrine carcinoma in which a gastroenteropancreatic origin is suspected (per pathologist or investigator discretion) will be eligible for the study.
  • Tumors must have a Ki-67 index greater than 20% and/or >20 mitotic figures/10 high-power fields.
  • Must have metastatic disease.
  • Must measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  • Any line of treatment (first line versus beyond first line).
  • Age >18 years.
  • Life expectancy of greater than 12 weeks.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
  • Must have adequate organ and marrow function.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Have had chemotherapy or radiotherapy within 3 weeks prior to entering the study.
  • Receiving any other investigational agents.
  • Untreated brain or meningeal metastases.
  • Prior treatment with 5-fluorouracil (5-FU), irinotecan or oxaliplatin.
  • Pre-treatment peripheral neuropathy greater than grade 1 per the CTCAE, version 4.0.
  • 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.
  • A secondary primary cancer (excluding baso/squamous cell carcinoma of skin) within 1 year.
  • Active viral hepatitis or autoimmune hepatitis. The work-up to confirm active hepatitis or autoimmune hepatitis will only be done if clinical suspicion based on investigator discretion.
  • Potential participants with childbearing potential who are not willing to use adequate contraception precautions during the study and for 3 months after stopping study chemotherapy.

Sites / Locations

  • H. Lee Moffitt Cancer Center and Research Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

FOLFIRINOX Treatment

Arm Description

Participants will receive modified FOLFIRINOX which consists of 85 mg/m^2 of oxaliplatin, 400 mg/m^2 of leucovorin over the first 2 hours, 165 mg/m^2 of irinotecan in a 90-minute infusion on day 1, followed by a continuous, 46-hour infusion of 5-FU at a dosage of 2,400 mg/m^2. A cycle will be repeated every 14 days. Granulocyte colony-stimulating factor (G-CSF) prophylaxis will be allowed after each cycle. Participants will undergo re-staging studies every 8 weeks. Participants will receive up to 12 cycles during the study. Additional cycles will be determined per investigators' discretion.

Outcomes

Primary Outcome Measures

Objective Radiographic Response Rate (ORR)
The primary efficacy endpoint is objective response rate as determined by radiology review, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response (CR): complete disappearance of all target lesions. Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum longest diameter. Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum). Stable Disease (SD): neither sufficient decrease to qualify for partial response nor sufficient increase to qualify for progressive disease.

Secondary Outcome Measures

Progression Free Survival (PFS)
PFS: from initiation date of therapy to disease progression or death. Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum).

Full Information

First Posted
February 2, 2017
Last Updated
November 24, 2020
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
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1. Study Identification

Unique Protocol Identification Number
NCT03042780
Brief Title
FOLFIRINOX in Metastatic High Grade Gastroenteropancreatic Neuroendocrine Carcinomas
Official Title
Phase II Trial of FOLFIRINOX in Metastatic High Grade Gastroenteropancreatic Neuroendocrine Carcinomas
Study Type
Interventional

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Terminated
Why Stopped
Slow accrual
Study Start Date
February 1, 2017 (Actual)
Primary Completion Date
January 3, 2018 (Actual)
Study Completion Date
September 7, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is evaluate the efficacy and safety of FOLFIRINOX in patients with gastroenteropancreatic high-grade neuroendocrine carcinomas. This is a prospective Phase II open-label trial, stratifying gastroenteropancreatic high grade neuroendocrine carcinomas participants equally into two cohorts (first-line versus beyond first-line).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastro-enteropancreatic Neuroendocrine Tumor, Pancreatic Cancer, Neuroendocrine Carcinomas of Pancreas, Islet Cell Carcinoma
Keywords
Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs), Metastatic, High grade, Pancreas, Neuroendocrine carcinoma of gastrointestinal tract

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
FOLFIRINOX Treatment
Arm Type
Experimental
Arm Description
Participants will receive modified FOLFIRINOX which consists of 85 mg/m^2 of oxaliplatin, 400 mg/m^2 of leucovorin over the first 2 hours, 165 mg/m^2 of irinotecan in a 90-minute infusion on day 1, followed by a continuous, 46-hour infusion of 5-FU at a dosage of 2,400 mg/m^2. A cycle will be repeated every 14 days. Granulocyte colony-stimulating factor (G-CSF) prophylaxis will be allowed after each cycle. Participants will undergo re-staging studies every 8 weeks. Participants will receive up to 12 cycles during the study. Additional cycles will be determined per investigators' discretion.
Intervention Type
Drug
Intervention Name(s)
FOLFIRINOX
Intervention Description
The FOLFIRINOX regimen consists of oxaliplatin given as a 2-hour intravenous infusion, immediately followed by leucovorin given as a 2-hour intra-venous infusion, with the addition, after 30 minutes, of irinotecan given as a 90-minute intravenous infusion. This study treatment is immediately followed by a continuous intravenous infusion of 5-Fluorouracil (5-FU) over a 46-hour period every 2 weeks.
Intervention Type
Drug
Intervention Name(s)
Granulocyte colony-stimulating factor (G-CSF)
Other Intervention Name(s)
Filgrastim, Cytokine
Intervention Description
The use of G-CSF will not be mandatory as primary prophylaxis, but will be allowed at investigators' discretion. If febrile neutropenia occurs, than the use of G-CSF will be mandatory after each following cycle of treatment.
Primary Outcome Measure Information:
Title
Objective Radiographic Response Rate (ORR)
Description
The primary efficacy endpoint is objective response rate as determined by radiology review, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response (CR): complete disappearance of all target lesions. Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum longest diameter. Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum). Stable Disease (SD): neither sufficient decrease to qualify for partial response nor sufficient increase to qualify for progressive disease.
Time Frame
Up to 36 months
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
PFS: from initiation date of therapy to disease progression or death. Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum).
Time Frame
Up to 36 months
Other Pre-specified Outcome Measures:
Title
Treatment Related Morbidity
Description
Safety analysis will be analyzed by collecting date on treatment-related morbidity and mortality. Investigators will collect data on frequency, type and severity of all adverse events that occur on or after Cycle 1, Day 1 according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE; Version 4.0).
Time Frame
Up to 36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically or cytologically confirmed neuroendocrine carcinoma of the gastrointestinal (GI) tract. Potential participants with unknown origin for the neuroendocrine carcinoma in which a gastroenteropancreatic origin is suspected (per pathologist or investigator discretion) will be eligible for the study. Tumors must have a Ki-67 index greater than 20% and/or >20 mitotic figures/10 high-power fields. Must have metastatic disease. Must measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Any line of treatment (first line versus beyond first line). Age >18 years. Life expectancy of greater than 12 weeks. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. Must have adequate organ and marrow function. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Have had chemotherapy or radiotherapy within 3 weeks prior to entering the study. Receiving any other investigational agents. Untreated brain or meningeal metastases. Prior treatment with 5-fluorouracil (5-FU), irinotecan or oxaliplatin. Pre-treatment peripheral neuropathy greater than grade 1 per the CTCAE, version 4.0. 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. A secondary primary cancer (excluding baso/squamous cell carcinoma of skin) within 1 year. Active viral hepatitis or autoimmune hepatitis. The work-up to confirm active hepatitis or autoimmune hepatitis will only be done if clinical suspicion based on investigator discretion. Potential participants with childbearing potential who are not willing to use adequate contraception precautions during the study and for 3 months after stopping study chemotherapy.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonathan Strosberg, M.D.
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States

12. IPD Sharing Statement

Learn more about this trial

FOLFIRINOX in Metastatic High Grade Gastroenteropancreatic Neuroendocrine Carcinomas

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