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

NCT02143219 | Completed Phase 2 Results DMC

• 2 other identifiers: ICO-N-2014-012014-000539-17
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Pancreatic Metastatic Cancer; Toxicity

Keywords

Pancreatic metastatic cancer; FOLFIRINOX; toxicity; efficacy

Outcome Measures

Primary Outcomes (1)

• Composite Safety and Early Efficacy Assessment in the First 34 Patients

  This outcome is a composite assessment combining safety and early efficacy signals in the first 34 enrolled patients. Safety is measured by the occurrence of grade ≥3 toxicities (NCI-CTCAE v4.0). Early efficacy is assessed by the presence or absence of tumor response according to predefined stopping rules. Both components contribute jointly to the decision-making criteria for continuation of the study. This description corresponds specifically to the data reported in the Results section.

  From treatment initiation through Week 12

Study Arms (1)

FOLFIRINOX

OTHER

FOLFIRINOX (D1-D15, for maximum 12 cycles) = Oxaliplatine + Folinic acid + Irinotecan + 5-FU

Drug: Oxaliplatine; Drug: Folinic acid; Drug: Irinotecan; Drug: 5-FU

Interventions

Oxaliplatine DRUG

Oxaliplatine : 85mg/m², 2-hours IV infusion (D1),

Also known as: Eloxatine®

FOLFIRINOX

Folinic acid DRUG

Folinic acid (FA): 400 mg/m² , 2-hour IV infusion (D1),

FOLFIRINOX

Irinotecan DRUG

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.

Also known as: Campto®

FOLFIRINOX

5-FU DRUG

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.

Also known as: 5-fluorouracile

FOLFIRINOX

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Histologically proven ductal pancreatic carcinoma
• Metastatic disease
• First-line treatment : No previous chemotherapy in metastatic stage but adjuvant treatment before relapse (secondary metastatic) is permitted, provide it has been administered more than 6 months before)
• Age of 70 yo or above
• Normal DPD enzyme level or partial defect (excluding total defect)
• Adequate bone marrow reserve: as indicated by : neutrophils \>1500/mm3, platelets \>100,000/ mm3, Hb \>10.0g/dL.
• Adequate Renal function as indicated by: MDRD creatinine clearance \> 50ml/min.
• Adequate hepatic function as indicated by: serum bilirubin \< 1.5 times the upper limit of normal, AST and ALT \< 2.5 times the upper limit of normal, or \< 5 times the upper limit of normal if liver metastases are present.
• Written informed consent must be obtained prior to protocol-specific procedures are being performed
• Patient is affiliated to a social security category

You may not qualify if:

• Other than ductal pancreatic carcinoma: namely endocrin tumors, acinar cells carcinoma, cystadenocarcinoma or adenocarcinoma of the ampulla of vater
• Non-metastatic but locally advanced pancreatic adenocarcinoma
• Complete DPD deficiency
• History of Cardiac failure or symptomatic coronary artery disease
• Autonomy Daily Living score by Katz \<4
• Prior treatment with FOLFIRINOX (adjuvant)
• Major comorbidity likely to be an obstacle to treatment
• Active or uncontrolled infection such as HIV or chronic B or C hepatitis
• Uncontrolled diabetes mellitus
• Prior peripheral neuropathy, grade \> 2
• Inflammatory bowel disease localized on the colon or rectum; bowel obstruction or severe uncontrolled diarrhea
• Previous or concomitant malignancies other than effectively treated carcinoma in situ of the cervix or non-melanoma skin cancer
• Hereditary fructose intolerance
• Persons deprived of liberty or under guardianship
• Any social, geographical or psychological condition which would compromise the ability to fully comply with the trial procedures and treatments

Sponsors & Collaborators

• Institut Cancerologie de l'Ouest: lead

Study Sites (6)

ICO Paul Papin

Angers, 49000, France

Location

CH Vendée

La Roche-sur-Yon, 85925, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

ICM (Val d'Aurelle)

Montpellier, 34298, France

Location

Centre Eugène marquis

Rennes, 35042, France

Location

ICO René Gauducheau

Saint-Herblain, 44805, France

Location

MeSH Terms

Interventions

Oxaliplatin; Leucovorin; Irinotecan; Fluorouracil

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Camptothecin; Alkaloids; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dr Sandrine HIRET
• Organization: Insitut de Cancérologie de l'Ouest

sandrine.hiret@ico.unicancer.fr

02 40 67 99 00

Study Officials

• Sandrine HIRET, MD

  Institut de Cancérologie de l'Ouest (ICO) - Nantes, France

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: May 14, 2014
• First Posted: May 21, 2014
• Study Start: July 31, 2014
• Primary Completion: November 25, 2020
• Study Completion: November 25, 2020
• Last Updated: April 15, 2026
• Results First Posted: April 15, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (6)