FOLFOX vs Gemcitabine in Patients With Metastatic Pancreatic Cancer Non-fit to FOLFIRINOX

NCT04167007 | Unknown Phase 3

• 2 other identifiers: D201801772019-001364-30
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pancreatic Adenocarcinoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS) at 24 months

  OS will be defined as the delay between the date of inclusion and the date of death (whatever the cause) or the date of last news if the patient is alive.

  At 24 months after inclusion

Secondary Outcomes (12)

• Objective response rate

  At 24 months after inclusion

• Disease control rate

  At 24 months after inclusion

• Duration of response

  Tumor assessment will be done every 2 cycles (1cycle = 28 days), assessed up to 24 months after inclusion

• Duration of disease control

  Tumor assessment will be done every 2 cycles (1 cycle = 28 days), assessed up to 24 months after inclusion

• Progression Free Survival (PFS)

  From inclusion to the date of first event (progression or death) or date of last news if the patient is alive without progression, assessed up to 60 months

Study Arms (2)

Group I

ACTIVE COMPARATOR

Gemcitabine at 1000 mg/m²

Drug: Gemcitabine

Group II

ACTIVE COMPARATOR

Oxaliplatin at 85 mg/m² ; Folinic acid 400 mg/m² (racemic form) or 200 mg/m² (L-form) and 5-FU 2400 mg/m²

Drug: FOLFOX

Interventions

Gemcitabine DRUG

Gemcitabine at 1000 mg/m² as intravenous (IV) infusion over 30-40 minutes on days 1, 8, and 15, followed by 1 week of rest, every 28 days

Group I

FOLFOX DRUG

Oxaliplatin at 85 mg/m² given as a 2 hours IV infusion on days 1 and 15; Folinic acid 400 mg/m² (racemic form) or 200 mg/m² (L-form) in 250 ml glucose 5% solution given as a 2 hours IV infusion on days 1 and 15; and 5-FU 2400 mg/m² administered as continuous 46-hour IV infusion on days 1-3 and 15-17, every 28 days.

Group II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated informed consent, and willing and able to comply with protocol requirements,
• Histologically or cytologically proven adenocarcinoma of the pancreas,
• 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,
• Metastatic disease confirmed (stage IV),
• No prior therapy for metastatic disease (in case of previous adjuvant therapy, interval from end of chemotherapy and relapse must be \>12 months),
• Age ≥18 years ,
• Patient non-fit for FOLFIRINOX,
• For patients with ECOG performance status (PS ) ≥2, an albuminemia level \>25 g/l is required,
• Haematological status: neutrophils (ANC) \>2x109/L; platelets \>100x109/L; haemoglobin ≥9g/dL,
• Adequate renal function: serum creatinine level \<150μM, and estimated creatinine clearance \>30ml/min,
• Adequate liver function: AST (SGOT) and ALT (SGPT) ≤2.5xULN (≤5xULN in case of liver metastases),
• Total bilirubin ≤3 x ULN,
• QT / QTc interval at baseline ECG (performed within 1 month before randomization) \< than 450 msec for men and \< than 470 msec for women,
• 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,
• 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.

You may not qualify if:

• 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),
• Local or locally advanced disease (stage I to III),
• Patient uses warfarin,
• Patient receiving concomitant radiotherapy,
• Electrolytic report uncontrolled: hypercalcemia and/or hypokalemia and/or hypomagnesemia,
• Pre-existing permanent neuropathy (NCI grade ≥2 ),
• Poor nutritional status
• Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
• Treatment with any other investigational medicinal product within 28 days prior to study entry,
• 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),
• Known or historical active infection with HIV, or known active infection untreated with hepatitis B or hepatitis C ,
• Known uncontrolled bacterial infection
• History or active interstitial lung disease (ILD),
• 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,
• Patients with known allergy to active substance or any excipient of study drugs,

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

APHP - Groupe Hospitalier Pitié-Salpêtrière

Paris, 75013, France

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Gemcitabine; Folfox protocol

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Jean-Baptiste BACHET, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jean-Baptiste BACHET, MD, PhD

CONTACT

0142161041 / 0142161045; jean-basptiste.bachet@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2019
• First Posted: November 18, 2019
• Study Start: July 20, 2020
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: August 18, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)