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

• Status: Active, not recruiting
• Trial end date: 2022-07-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institut Cancerologie de l'Ouest
• Treatments: Folic Acid; Irinotecan; Leucovorin; Levoleucovorin; Oxaliplatin

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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