Informations générales (source: ClinicalTrials.gov)
Randomized Phase 3 Trial Comparing FOLFOX to Gemcitabine in Metastatic First-line in Patients With Pancreatic Adenocarcinoma and Non-fit for FOLFIRINOX
Interventional
Phase 3
Assistance Publique - Hôpitaux de Paris (Voir sur ClinicalTrials)
juillet 2020
juillet 2025
13 septembre 2025
Pancreatic adenocarcinoma (PAC) incidence increases regularly in Western countries and it
is expected to become the second leading cause of cancer-related mortality in 2020. The
prognosis of this disease remains very poor with an overall 5-year survival rate less
than 5%.
The FOLFIRINOX regimen (5-fluorouracil [5-FU], folinic acid, irinotecan, and oxaliplatin)
and the combination of nab-paclitaxel with gemcitabine demonstrated to be more effective
than gemcitabine alone, and are both validated as standard first-line treatment options
for metastatic PAC. However, the use of FOLFIRINOX is limited to patients with ECOG
performance status (PS) 0-1 and aged less than 75 years. Nab-paclitaxel is currently not
reimbursed in France.
Etablissements
Critères
Tous
Inclusion Criteria:
1. Signed and dated informed consent, and willing and able to comply with protocol
requirements,
2. Histologically or cytologically proven adenocarcinoma of the pancreas,
3. In absence of histologically or cytologically proven adenocarcinoma, a cluster of
clinical, biological and radiological arguments consistent with the diagnosis: among
these, a hypodense pancreatic tumor at CT and a Ca 19-9 greater than 500 UI/ml are
essential prerequisites,
4. Metastatic disease confirmed (stage IV),
5. No prior therapy for metastatic disease (in case of previous adjuvant therapy,
interval from end of chemotherapy and relapse must be >12 months),
6. Age ≥18 years ,
7. Patient non-fit for FOLFIRINOX,
8. For patients with ECOG performance status (PS ) ≥2, an albuminemia level >25 g/l is
required,
9. Haematological status: neutrophils (ANC) >2x109/L; platelets >100x109/L; haemoglobin
≥9g/dL,
10. Adequate renal function: serum creatinine level <150μM, and estimated creatinine
clearance >30ml/min,
11. Adequate liver function: AST (SGOT) and ALT (SGPT) ≤2.5xULN (≤5xULN in case of liver
metastases),
12. Total bilirubin ≤3 x ULN,
13. QT / QTc interval at baseline ECG (performed within 1 month before randomization) <
than 450 msec for men and < than 470 msec for women,
14. Baseline evaluations performed before randomization: clinical and blood evaluations
no more than 2 weeks (14 days) prior to randomization, tumor assessment (CT-scan or
MRI, evaluation of non-measurable lesions) no more than 3 weeks (21 days) prior to
randomization,
15. Female patients must be surgically sterile, or be postmenopausal, or must commit to
using reliable and appropriate methods of contraception during the study and during
at least six months after the end of study treatment (when applicable). All female
patients with reproductive potential must have a negative pregnancy test (β HCG)
within 7 days prior to starting protocol treatment. Breastfeeding is not allowed.
16. Male patients must agree to use effective contraception in addition to having their
partner use a contraceptive method as well during the trial and during at least six
months after the end of the study treatment
17. Affiliation to a French social security system (recipient or assign).
1. Signed and dated informed consent, and willing and able to comply with protocol
requirements,
2. Histologically or cytologically proven adenocarcinoma of the pancreas,
3. In absence of histologically or cytologically proven adenocarcinoma, a cluster of
clinical, biological and radiological arguments consistent with the diagnosis: among
these, a hypodense pancreatic tumor at CT and a Ca 19-9 greater than 500 UI/ml are
essential prerequisites,
4. Metastatic disease confirmed (stage IV),
5. No prior therapy for metastatic disease (in case of previous adjuvant therapy,
interval from end of chemotherapy and relapse must be >12 months),
6. Age ≥18 years ,
7. Patient non-fit for FOLFIRINOX,
8. For patients with ECOG performance status (PS ) ≥2, an albuminemia level >25 g/l is
required,
9. Haematological status: neutrophils (ANC) >2x109/L; platelets >100x109/L; haemoglobin
≥9g/dL,
10. Adequate renal function: serum creatinine level <150μM, and estimated creatinine
clearance >30ml/min,
11. Adequate liver function: AST (SGOT) and ALT (SGPT) ≤2.5xULN (≤5xULN in case of liver
metastases),
12. Total bilirubin ≤3 x ULN,
13. QT / QTc interval at baseline ECG (performed within 1 month before randomization) <
than 450 msec for men and < than 470 msec for women,
14. Baseline evaluations performed before randomization: clinical and blood evaluations
no more than 2 weeks (14 days) prior to randomization, tumor assessment (CT-scan or
MRI, evaluation of non-measurable lesions) no more than 3 weeks (21 days) prior to
randomization,
15. Female patients must be surgically sterile, or be postmenopausal, or must commit to
using reliable and appropriate methods of contraception during the study and during
at least six months after the end of study treatment (when applicable). All female
patients with reproductive potential must have a negative pregnancy test (β HCG)
within 7 days prior to starting protocol treatment. Breastfeeding is not allowed.
16. Male patients must agree to use effective contraception in addition to having their
partner use a contraceptive method as well during the trial and during at least six
months after the end of the study treatment
17. Affiliation to a French social security system (recipient or assign).
1. History or evidence upon physical examination of CNS metastasis unless adequately
treated (e.g. non irradiated CNS metastasis, seizure not controlled with standard
medical therapy),
2. Local or locally advanced disease (stage I to III),
3. Patient uses warfarin,
4. Patient receiving concomitant radiotherapy,
5. Electrolytic report uncontrolled: hypercalcemia and/or hypokalemia and/or
hypomagnesemia,
6. Pre-existing permanent neuropathy (NCI grade ≥2 ),
7. Poor nutritional status
8. Known dihydropyrimidine dehydrogenase (DPD) total or partial deficiency (DPD
activity dosage at inclusion visit),
9. Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted
therapy, immunotherapy),
10. Treatment with any other investigational medicinal product within 28 days prior to
study entry,
11. Other serious and uncontrolled non-malignant disease (eg. active infection requiring
systemic therapy, coronary stenting or myocardial infarction or stroke in the past 6
months),
12. Known or historical active infection with HIV, or known active infection untreated
with hepatitis B or hepatitis C ,
13. Known uncontrolled bacterial infection
14. History or active interstitial lung disease (ILD),
15. Other concomitant or previous malignancy, except: i/ adequately treated in-situ
carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin,
iii/ cancer in complete remission for >5 years,
16. Patients with known allergy to active substance or any excipient of study drugs,
17. Allergy to iodinated contrast product
18. Concomitant administration of live, attenuated virus vaccine and concomitant
administration of prophylactic phenytoin.
19. Patients under legal protection or unable to consent
20. Participation in another interventional research