Sequential Treatment With GEMBRAX and Then FOLFIRINOX Followed by Stereotactic MRI-guided Radiotherapy in Patients With Locally Advanced Pancreatic Cancer

Launched by INSTITUT DU CANCER DE MONTPELLIER - VAL D'AURELLE · Sep 29, 2020

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment approach for patients with locally advanced pancreatic cancer, which is a type of cancer that cannot be removed through surgery. The study is testing a combination of two chemotherapy regimens—Gabrinox (a mix of Gemcitabine and Abraxane) followed by FOLFIRINOX (which includes several different chemotherapy drugs)—to see if this intensified treatment helps more patients. After the chemotherapy, patients who do not see their cancer progress will receive a specialized type of radiation therapy guided by MRI to target the tumor more precisely.

To be eligible for this trial, participants need to be between 18 and 75 years old and have a confirmed diagnosis of pancreatic adenocarcinoma that is not metastasized (meaning it hasn't spread to other parts of the body). They should also meet certain health criteria, such as having a good overall health status and specific blood test results. Participants can expect to receive close medical supervision throughout the treatment, and they will be part of a study aiming to improve outcomes for patients with this challenging condition. It’s important to note that this trial excludes individuals with certain health issues or previous treatments for pancreatic cancer, ensuring that the study focuses on a specific group of patients.

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Eligibility criteria

• Inclusion Criteria:
• • 1. Patient aged from 18 to 75 years at the date of signature of the consent form
• • 2. Histologically or cytologically proven pancreatic adenocarcinoma
• • 3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• • 4. Non-resectable tumour according to the National Comprehensive Cancer Network (NCCN) 1.2015 recommendations after external review of imaging data by multidisciplinary experts.
• • 5. Non-metastatic cancer confirmed by thorax-abdomen-pelvis computerized tomography (CT) scan and liver MRI
• • 6. SMART feasibility confirmed by centralized review
• • 7. Uracilemia \< 16 ng/ml
• 8. Hematological assessment within 14 days before inclusion, defined by:
• • Neutrophils ≥ 2 000/mm3 (2 × 109/L);
• • Platelets ≥ 100 000/mm3 (100 × 109/L);
• • Hemoglobin ≥ 9 g/dl
• 9. Liver function (within 14 days before inclusion) defined by:
• • ASpartate Transaminase (AST) and ALanine Transaminase (ALT) ≤ 2.5 x Upper Limit of Normal (ULN);
• • Total bilirubin ≤ 1.5 x ULN. Patients with a metallic biliary prosthesis due to biliary obstruction caused by the cancer may be included, if: a CT scan with injection of contrast medium and thin pancreas sections was performed before placing the biliary prosthesis, the bilirubin level after prosthesis fitting decreased to ≤20 m /L (≤34 μmol/l), and in the absence of cholangitis.
• • 10. Creatininaemia within the reference limits, or calculated clearance ≥50 ml/min for patients with a serum creatinine value above or below the reference values (clearance calculated using the Chronic Kidney Disease EPIdemiology collaboration (CKDEPI formula).
• • 11. Serum calcium AND magnesium AND potassium ≥ Lower Limit Normal (LLN and ≤ 1.2 x Upper Limit Normal (ULN)
• • 12. Cancer Antigen (CA 19.9) \<500 IU/mL (without cholestasis). Patients with CA 19.9 between 500 IU/mL and 1000 IU/mL can be included if the Positron Emission Tomography (PET) scan and peritoneal MRI (optional) do not detect any distant fixation, indicative of metastasis. Patients with CA 19.9 ≥ 1000 IU/mL cannot be included.
• • 13. Sexually active patients must use a contraceptive method considered adequate and suitable by the investigator during the entire period of administration of the study treatment and up to 6 months after the treatment end, for female and male patients.
• • 14. Signature of the consent form before any study-specific procedure.
• • 15. Covered by the French health insurance.
• Exclusion Criteria:
• • 1. Any previous treatment for pancreatic cancer (e.g. chemotherapy, radiotherapy, surgery, targeted therapy, experimental therapy)
• • 2. Gilbert's syndrome or homozygous Uridine DiPhosphate Glucuronosyl Transferase 1 A1 (UGT1A1 \* 28)
• • 3. Other concomitant cancer or history of cancer, except for treated in situ cancer of the cervix , basal cell or squamous cell carcinoma, superficial bladder tumour (Ta, Tis, and T1), or good-prognosis tumour cured without chemotherapy and without signs of disease in the 3 years before inclusion
• • 4. History of radiotherapy that causes a foreseeable 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 in the past 6 months.
• • 6. Peripheral neuropathy ≥ grade 2
• • 7. ECG with QTcorrected (QTc) interval longer than 450 ms for men and longer than 470 ms for women
• • 8. Contraindication to MRI and MRI-guided radiotherapy
• • 9. History of chronic inflammatory disease of the colon or rectum
• • 10. Any other concomitant and not controlled serious illness or disturbance 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 disorder)
• • 11. Intolerance or allergy to one of the study drugs (gemcitabine, Nab-paclitaxel, oxaliplatin, irinotecan, 5-FU) or to one of their excipients (e.g. fructose) listed in the Contraindications or Warnings sections and Special precautions of the Summary of Product Characteristics (SmPC) or prescription information
• • 12. Legal incapacity (patient under guardianship or wardship)
• • 13. Pregnant or breastfeeding woman. Fertile women must have a negative pregnancy test (serum β-hCG) performed 72 hours before inclusion
• • 14. Patient using vitamin K antagonists (Coumadin...) (possible modification of the treatment before inclusion)
• • 15. Active and uncontrolled bacterial or fungal infection that requires systemic treatment.
• • 16. Know active HIV infection
• • 17. History of peripheral arterial disease (e.g. lameness, Buerger's disease).
• • 18. Patient who received a attenuated live vaccine in the 10 days before inclusion
• • 19. Patient with history of pulmonary fibrosis or interstitial pneumonia.
• • 20. Inability to attend the follow-up visits due to geographic, social or mental reasons.
• • 21. Participation in another clinical study with a research product during the last 30 days before inclusion.