Induction FOLFIRINOX Followed by Chemoradiation in Locally Advanced Pancreatic Cancer

Phase 2

• Conditions: Pancreatic Cancer
• Interventions: Drug: Chemotherapy; Radiation: Radiation

• Registration Number: NCT05399394
• Lead Sponsor: Campus Bio-Medico University

Brief Summary

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).

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 Timeline

• Study Start: 2016-07-01
• Primary Completion: 2022-04-01
• Study First Submitted: 2022-04-06
• Status Verified: 2022-05
• Study First Submitted QC: 2022-05-30
• Last Update Submitted: 2022-05-30
• Study Completion: 2022-06-01
• Study First Posted: 2022-06-01
• Last Update Posted: 2022-06-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LAPC patients	Chemotherapy	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.
LAPC patients	Radiation	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.

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-Emergent Adverse Events	four months	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	3 years	Overall Survival (OS) is determined from the day of the histological diagnosis. OS curves are calculated with the Kaplan-Meier method.
Progression-free survival	3 years	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.
Metastases-free survival	3 years	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.
Incidence of Local-regional Tumor Control	3 years	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.