Sequential treatment with Gemcitabine/Nab-Paclitaxel then Folfirinox followed by MRI-guided radiotherapy in patients with locally advanced adenocarcinoma of the pancreas

Phase 1

• Conditions: ocally advanced adenocarcinoma of pancreas; MedDRA version: 21.0Level: LLTClassification code 10033600Term: Pancreatic adenocarcinoma non-resectableSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-002517-18-FR
• Lead Sponsor: Institut régional du cancer de Montpellier (ICM)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-07-22
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 103

Inclusion Criteria

1.Patient between 18 and 75 years of age on the date of signing the consent form.
2.Histologically or cytologically proven pancreatic adenocarcinoma.
3.Eastern Cooperative Oncology Group (ECOG) performance status = 1.
4.Non-resecurability criteria, according to NCCN 1.2015 recommendations validated during the centralized proofreading.
5.Non-metastatic patient confirmed by TAP scan and hepatic MRI.
6.Feasibility of MRI-guided radiotherapy confirmed by central review.
7.Uracilemia < 16 ng/ml.
8.Hematologic workup obtained within 14 days prior to inclusion defined by:
-Neutrophils = 1 500/mm3 (1.5 × 109/L);
-Platelets = 100,000/mm3 (100 × 109/L);
-Haemoglobin = 9 g/dl
9.Liver function (obtained within 14 days prior to inclusion) defined by :
-AST and ALT = 2.5 x Upper Limit of the Standard (ULN);
-Total bilirubin = 1.5 x ULN; Patients with a metallic biliary prosthesis due to biliary obstruction from cancer may be included provided that a CT scan with contrast injection and fine cuts to the pancreas has been performed prior to the insertion of the biliary prosthesis, the bilirubin level after insertion of the prosthesis decreases to = 20 mg/L (= 34 µmol/l), and in the absence of angiocholitis.
10.Creatinine within the limits of the norm or calculated clearance = 50ml/min for patients with a creatinine value above or below the values of the norm (clearance calculated by the CKD-EPI formula).
11.Calcaemia = LIN and = 1.2 x ULN; magnesia = LIN and = 1.2 x ULN; kalaemia = LIN and = 1.2 x ULN.
12.CA 19.9 < 190 IU/mL (no icteric cholestasis). If CA 19.9 between 190 IU/mL and 500 IU/mL, the patient may be included if PET scan and peritoneal MRI do not reveal any distant metastasis indicating metastasis. If CA 19.9 = 500 IU/ML the patient is non-included.
13.If the patient is sexually active, the patient must agree to use contraception deemed adequate and appropriate by the investigator during the entire period of study drug administration and up to 3 months after discontinuation of treatment. In addition, male and female patients should use a method of contraception after the end of treatment as recommended in the Summary of Product Characteristics or the prescribing information for the product provided in the study manual.
14.Signature of consent prior to any study-specific procedure.
15.Affiliated with a French health insurance plan.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Any previous treatment for pancreatic cancer (chemotherapy, radiation therapy, surgery, targeted therapy or experimental therapy...)
2.Gilbert's syndrome known or homozygous for UGT1A1*28 validated
3.Other concomitant cancer or a history of cancer, with the exception of treated cervical cancer in situ, basal cell or squamous cell skin carcinoma, superficial bladder tumour (Ta, Tis, and T1) or a good prognosis tumour treated curatively without chemotherapy and without evidence of disease within 3 years prior to inclusion.
4.History of radiotherapy with predictable overlap with the radiotherapy treatment under study (history of abdominal irradiation).
5.Patients with high cardiovascular risk, including, but not limited to, coronary stent or myocardial infarction within the last 6 months.
6.Peripheral neuropathy = grade 2.
7.ECG with a QTc interval greater than 450 ms for males and greater than 470 ms for females.
8.Contraindication to MRI and MRI-guided radiation therapy.
9.History of chronic inflammatory disease of the colon or rectum.
10.Any other serious concomitant uncontrolled disease or disorder that may interfere with the patient's participation in the study and safety during the study (e.g., severe liver, kidney, lung, metabolic, or psychiatric disorders).
11.Intolerance or allergy to one of the study drugs (gemcitabine, Abraxane®, oxaliplatin, irinotecan, 5-FU) or to an excipient of one of the drugs (example: fructose) described in the Contraindications or Warnings and Special Precautions sections of the SPC or Prescribing Information.
12.Legal incapacity (patient under curatorship or guardianship).
13.Pregnant or breastfeeding woman. If a patient is of childbearing age, she must have a negative pregnancy test (serum ß-hCG) documented 72 hours prior to inclusion.
14.Patients using VKA (Coumadin...) (possible modification of treatment before inclusion).
15.Uncontrolled active bacterial or viral or fungal infection requiring systemic treatment.
16.Previous or known HIV infection.
17.History of peripheral arterial disease (e.g., claudication, Leo Buerger's disease).
18.Patient who received live attenuated vaccine within 10 days prior to inclusion.
19.Patients with a history of pulmonary fibrosis or interstitial pneumonia.
20.Inability to undergo medical follow-up of the trial for geographical, social or psychological reasons.
21.Participation in another clinical study with an investigational product within the last 30 days prior to inclusion.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified