NCT02143219

Efficacy and Tolerance Evaluation in FOLFIRINOX Dose Adjusted in Elderly Patients With a Metastatic Pancreatic Cancer

Phase-2 Study Evaluating Overall Response Rate (Efficacy) and Autonomy Daily Living Preservation (Tolerance) of "FOLFIRINOX " Pharmacogenetic Dose Adjusted, in Elderly Patients (70 yo. or Older) With a Metastatic Pancreatic Adenocarcinoma.

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 72 (actual)
• Sponsor: Institut Cancerologie de l'Ouest · Academic / Other
• Sex: All
• Age: 70 Years
• Healthy volunteers: Not accepted

Summary

Metastatic pancreatic carcinomas represent the 5th cause of cancer death in France (#8000 per year). The median age at diagnosis is 69 and 74 in male and female respectively. When the 5-Fluorouracile has been used as a single agent with a limited efficacy during more than 20 years, the onset of gemcitabine in 1995 has led to a moderate increase of median survival (from 4.41 to 5.65 months) and overall survival at 1 year (2 versus 18%). Recently, in a phase II followed by a phase-III study, a French collaborative group has demonstrated the benefit of "FOLFIRINOX " regimen versus gemcitabine alone, in terms of median survival (11.1 versus 6.8 months), progression-free survival (6.4 versus 3.3 months) and response rate (31.6 versus 9.4%). Although more hematologic (neutropenia) and GI toxicities were observed, FOLFIRINOX was acceptable as a new standard regimen for the majority of patients under the age of 70 with a good Performans Status. To reduce the toxicity of FOLFIRINOX in elderly patients (\> 70 yo), pharmacogenetic monitoring of 5-FU and Irinotecan key metabolism enzymes (DPD and UGTA1) may be easily performed. The methodology of the study is to use the Bryant \& Day statistical method, allowing to consider simultaneously as principal objective, the response rate (efficacy) and the tolerance (preservation of autonomy daily living, Katz index): this design is particularly fitting in a study for elderly patients who represent half of the pancreatic carcinoma population.

Detailed description

METHODOLOGY : Phase II study, opened, multicentric MAIN OBJECTIVE : The main objective is the simultaneous evaluation of the objective rate of answer and toxicity of her(it) of the protocol FOLFIRINOX administered to doses adapted at patients of 70 and more years old. SECONDARY OBJECTIVE : * Efficiency evaluation; * Tolerance evaluation; * Quality of Life (QoL) and clinical profit. STATISTICAL ANALYSIS: An analysis in two stages is planned, according to the method of Bryant and Day with a risk ß 5 % to reject wrongly an effective treatment and of acceptable toxicity and a risk a=10 % to accept wrongly a not rather effective or too toxic treatment. The study will be considered as successful if: * we obtain at least 11 tumoral answers and * maxi 30 patients on 72 are in loss of autonomy (decrease of their ADL). * All the patients who will have received at least an injection will be eligible for the evaluation of the toxicity * The evaluation of the efficiency will be made after 3 cures at least unless early termination where the scanner will be anticipated. * All the toxicity will be increased according to criteria of toxicity NCI-CTC v4.0. * The evaluation of the tumoral answer (CR, PR and SD) will be made according to the criteria RECIST-v1.1.

Conditions

• Pancreatic Metastatic Cancer
• Toxicity

Interventions

Type	Name	Description
DRUG	Oxaliplatine	Oxaliplatine : 85mg/m², 2-hours IV infusion (D1),
DRUG	Folinic acid	Folinic acid (FA): 400 mg/m² , 2-hour IV infusion (D1),
DRUG	Irinotecan	Irinotecan (at the dosage determined by the UGT1A1 status), 90 min IV infusion starting 30 min after the FA starts * Homozygous 6/6 or 6/7: irinotecan will start at 150 mg/m², then will be increased according to clinical/biological tolerance by 10% steps, at each cycle, up to 180 mg/m² at max. * Homozygous 7/7: irinotecan will start at 130 mg/m² in the first cycle then be increased up to a max of 150 mg/m², by 10% steps, according to tolerance.
DRUG	5-FU	5-FU (according to the DPD pharmacogenetic status), continuous IV infusion of 46 hours, starting at the end of FA infusion: * If no DPD deficiency, 5-FU start at 1600 mg/m² and can be modulated according to clinical/biological tolerance after each course, i.e., 1800 mg/m² the 2nd course and 2000 mg/m² the 3rd one * If partial DPD deficiency: 5-FU start at 1200 mg/m² and can be increased up to 1800, then 2000 if the clinical/biological tolerance are good at the 2nd and 3rd course.

Timeline

• Start date: 2014-07-31
• Primary completion: 2020-11-25
• Completion: 2020-11-25
• First posted: 2014-05-21
• Last updated: 2026-04-15
• Results posted: 2026-04-15

Locations

6 sites across 1 country: France