FOLFIRINOX in Metastatic High Grade Gastroenteropancreatic Neuroendocrine Carcinomas

NCT03042780 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: MCC-18675
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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).

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 36 months

Secondary Outcomes (1)

• Progression Free Survival (PFS)

  Up to 36 months

Other Outcomes (1)

• Treatment Related Morbidity

  Up to 36 months

Study Arms (1)

FOLFIRINOX Treatment

EXPERIMENTAL

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.

Drug: FOLFIRINOX; Drug: Granulocyte colony-stimulating factor (G-CSF)

Interventions

FOLFIRINOX DRUG

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.

FOLFIRINOX Treatment

Granulocyte colony-stimulating factor (G-CSF) DRUG

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.

Also known as: Filgrastim, Cytokine

FOLFIRINOX Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Gastro-enteropancreatic neuroendocrine tumor; Pancreatic Neoplasms; Carcinoma, Islet Cell; Neoplasm Metastasis

Interventions

folfirinox; Granulocyte Colony-Stimulating Factor; Filgrastim; Cytokines

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

Study terminated early due to inability to accrue, leading to small number of participants analyzed.

Results Point of Contact

• Title: Jonathan Strosberg, MD
• Organization: H Lee Moffitt Cancer Center and Research Institute

Jonathan.Strosberg@moffitt.org

813-745-7257

Study Officials

• Jonathan Strosberg, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

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: February 2, 2017
• First Posted: February 3, 2017
• Study Start: February 1, 2017
• Primary Completion: January 3, 2018
• Study Completion: September 7, 2018
• Last Updated: November 27, 2020
• Results First Posted: December 11, 2018

Record last verified: 2020-11

Locations

US (1)