Induction FOLFIRINOX Followed by Chemoradiation in Locally Advanced Pancreatic Cancer (FOLRT)

There is no a clear consensus regarding the optimal treatment strategy of locally advanced pancreatic cancer. There is a potential role for neoadjuvant therapy to treat micrometastatic disease with chemotherapy, as well as for the treatment of local disease with radiotherapy. The investigators evaluated the safety and efficacy of induction FOLFIRINOX followed by a high weekly dose of gemcitabine concurrent to radiation therapy in patients with borderline resectable and unresectable locally advanced pancreatic cancer (LAPC).

Study Overview

• Status: Active, not recruiting
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Chemotherapy; Radiation: Radiation

Detailed Description

Continued optimization in multimodality therapy and an accurate patient selection remain crucial points for the appropriate treatment of patients with pancreatic cancer. In all patients an accurate pre-treatment staging was performed, including multilayer CT scan, positron emission computed tomography (PET-CT) with 18F-2-fluoro-2-deoxy-D-glucose (FDG) and laparoscopy with peritoneal washing. Patients with the evidence of metastatic disease were excluded, and thus only a small number of patients was consequently enrolled with this approach.The induction phase of the treatment plan was designed to administer FOLFIRINOX protocol (oxaliplatin 85 mg/mq and irinotecan 180 mg/mq plus leucovorin 400 mg/mq followed by bolus FU 400 mg/mq on day 1, then FU 2,400 mg/mq as a 46-hour continuous infusion) every 14 days for four cycles. In the combined phase of the treatment radiotherapy target volumes were established by CT scan and PET-CT scan. Concurrent chemotherapy consisted of gemcitabine at the dose of 600 mg/mq weekly. Four weeks after the completion of radiochemotherapy, restaging including CT scan and PET-CT scan was performed. Tumor response was defined in accordance with the World Health Organization (WHO) definition through CT scan and PET-CT scan. Surgery was considered in patients whose tumors were technically resectable. After resection, patients were evaluated every three months by means of a standard surveillance protocol that included history and physical examination, cross-sectional imaging and measurement of serum markers, and the intervals were extended to six months after two years

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• proven cytological or histological diagnosis of pancreatic ductal adenocarcinoma;
• borderline resectable or unresectable pancreatic tumours;
• no previous radiochemotherapy to abdomen;
• 0-I Eastern Cooperative Oncology Group (ECOG) performance status;
• adequate cardiac, liver and kidney function and a good bone marrow reserve.

Exclusion Criteria:

• resectable and metastatic disease;
• previous or concomitant malignant disease;
• one or more of the following clinical conditions: infection, pregnancy or breast-feeding, liver failure, kidney failure, Pa O2 < 65 mmHg, Pa carbon dioxide (CO2) > 40 mmHg, mental disability.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: LAPC patients; Patients treated with induction FOLFIRINOX; for patients without disease progression as detected through restaging exams, chemotherapy was followed by chemoradiation which consisted of conformal radiation therapy and concurrent gemcitabine at the dose of 600 mg/mq weekly.

Drug: Chemotherapy; The induction phase of the treatment plan was designed to administer FOLFIRINOX protocol (oxaliplatin 85 mg/mq and irinotecan 180 mg/mq plus leucovorin 400 mg/mq followed by bolus fluorouracil (FU) 400 mg/mq on day 1, then FU 2,400 mg/mq as a 46-hour continuous infusion) every 14 days for four cycles. In the combined phase, concurrent chemotherapy consisted of weekly gemcitabine at the dose of 600 mg/mq.; Other Names: Induction therapy; Radiation: Radiation; Radiotherapy target volumes are established by CT scan and PET-CT scan. Radiotherapy is delivered with a total dose of 54-59 Gy with fractionation of 1.8 Gy daily for 5 days a week. The Planning Target Volume (PTV) is defined by the Clinical Target Volume (CTV) with a safety margin to include organ motion and set-up errors. Organs at risk for radiation-induced side effects are contoured on the dose planning CT and dose volume histograms (DVH) are calculated. All treatments are delivered with a multifield isocentric technique using a multileaf collimator. A quality-control protocol are applied through cone-beam computed tomography systems (CBCT) for all patients to evaluate the precision of the set-up.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events	During treatment, patients are evaluated through a directed history, weekly physical examination and blood exams. The occurrence and nature of any adverse events are recorded in accordance with the National Cancer Institute Common Toxicity Criteria (version 4.02) scale. When multiple treatment-related adverse events of the same type occurred in the same patient, only the most severe ones are reported. Subsequently, the dose of chemotherapy is adjusted according to the number of occurrences of grade 2 or greater events.	four months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall Survival (OS) is determined from the day of the histological diagnosis. OS curves are calculated with the Kaplan-Meier method.	3 years
Progression-free survival	Progression-free survival (PFS) is obtained from the beginning of treatment to the observation of progression/recurrence, or to last follow-up if no event is observed. PFS curves are calculated with the Kaplan-Meier method.	3 years
Metastases-free survival	Metastases-free survival (MFS) is obtained from the beginning of treatment to the observation of distant progression, or to last follow-up if no event is observed. MFS curves are calculated with the Kaplan-Meier method.	3 years
Incidence of Local-regional Tumor Control	Patients are not considered to have local-regional control unless they achieve at least a partial response of their primary tumor or stable disease by imaging. Patients who do not achieve objective response are considered to have local-regional failure. Local-regional control rates are analyzed using the Kaplan-Meier method.	3 years

Collaborators and Investigators

• Sponsor: Campus Bio-Medico University
• Investigators: Principal Investigator: Michele Fiore, MD, Campus Bio-Medico University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): April 1, 2022
• Study Completion (Anticipated): June 1, 2022

Study Registration Dates

• First Submitted: April 6, 2022
• First Submitted That Met QC Criteria: May 30, 2022
• First Posted (Actual): June 1, 2022

Study Record Updates

• Last Update Posted (Actual): June 1, 2022
• Last Update Submitted That Met QC Criteria: May 30, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: chemoradiation; FOLFIRINOX
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: 2016-000696-25

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No