Gastro-enteropancreatic Neuroendocrine Tumor, Pancreatic Cancer, Neuroendocrine Carcinomas of Pancreas, Islet Cell Carcinoma
Conditions
Keywords
Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs), Metastatic, High grade, Pancreas, Neuroendocrine carcinoma of gastrointestinal tract
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).
Interventions
DRUGFOLFIRINOX
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.
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.
Sponsors
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Radiographic Response Rate (ORR) | Up to 36 months | 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
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Up to 36 months | 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). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Treatment Related Morbidity | Up to 36 months | 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). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| FOLFIRINOX Treatment 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. Participants will receive up to 12 cycles during the study. Additional cycles will be determined per investigators' discretion. | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | FOLFIRINOX Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 2 |
| other Total, other adverse events | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 |
Outcome results
Primary
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.
Time frame: Up to 36 months
Population: Due to low accrual, study was halted prematurely. No data, as no patients were analyzed.
Secondary
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).
Time frame: Up to 36 months
Population: No data displayed because Outcome Measure has zero total participants analyzed.
Other Pre-specified
Treatment Related Morbidity
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
Population: No data displayed because Outcome Measure has zero total participants analyzed.