Comparing FOLFOX and Gemcitabine for Metastatic Pancreatic Cancer Patients Not Fit for FOLFIRINOX

Randomized Phase 3 Trial Comparing FOLFOX to Gemcitabine in Metastatic First-line in Patients With Pancreatic Adenocarcinoma and Non-fit for FOLFIRINOX

This study is testing whether the FOLFOX treatment works better than gemcitabine for people with advanced pancreatic cancer who can't take another common treatment.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 400 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Paris)
• Trial ID: NCT04167007 on ClinicalTrials.gov

What this trial studies

This phase III trial is an open-label, multicenter, randomized study that compares the effectiveness of FOLFOX versus gemcitabine in treating patients with metastatic pancreatic adenocarcinoma who are not suitable for FOLFIRINOX. The study aims to enroll 400 patients and will assess overall survival at 24 months as the primary endpoint, along with secondary objectives including response rates, progression-free survival, and quality of life. Participants will be randomized into two treatment arms, receiving either FOLFOX or gemcitabine, with careful monitoring of safety and efficacy throughout the trial.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with histologically confirmed metastatic pancreatic adenocarcinoma who are not fit for FOLFIRINOX.

Not a fit: Patients with early-stage pancreatic cancer or those who are fit for FOLFIRINOX may not benefit from this study.

Why it matters

Potential benefit: If successful, this trial could provide a more effective treatment option for patients with metastatic pancreatic cancer who cannot tolerate FOLFIRINOX.

How similar studies have performed: Other studies have shown promising results with similar treatment approaches, but this specific comparison of FOLFOX and gemcitabine in this patient population is novel.

Eligibility criteria

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).

Exclusion Criteria:

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

Where this trial is running

Paris

• APHP - Groupe Hospitalier Pitié-Salpêtrière — Paris, France (Recruiting)

Study contacts

• Principal investigator: Jean-Baptiste BACHET, MD, PhD — Assistance Publique - Hôpitaux de Paris
• Study coordinator: Jean-Baptiste BACHET, MD, PhD

Conditions Pancreatic Adenocarcinoma; Pancreatic adenocarcinoma; Metastasis; Gemcitabine; FOLFOX; first-line