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

NCT04570943 | Recruiting Phase 2 DMC

• 1 other identifier: PROICM 2020-04 GAB
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 9

Brief Summary

The aim of this study is to demonstrate the efficacy of intensified and sequential chemotherapy (Gabrinox) comprising Gembrax regimen (Gemcitabine-Abraxane) followed by the Folfirinox regimen (5FU, Oxaliplatin and Irinotecan) in patients with locally advanced pancreatic adenocarcinoma. The study will also demonstrate the feasibility of combining this intensified chemotherapy with MRI-guided stereotactic radiotherapy in non-progressive patients after the chemotherapy by Gabrinox regimen.

Conditions

Locally Advanced Pancreatic Adenocarcinoma

Keywords

Pancreatic; cancer

Outcome Measures

Primary Outcomes (2)

• Rate of non-progression at 4 months

  (Sequence 1 success = chemotherapy) according to the RECIST v1.1 criteria

  4 months

• Acute gastrointestinal non-toxicity rate

  Absence of toxicity of grade ≥3 related to radiotherapy within 90 days, evaluated using the NCI-CTCAE v5.0 classification (sequence 2 success = radiotherapy)

  90 days

Secondary Outcomes (20)

• Assessment of adverse events due to chemotherapy by using the NCI-CTCAE version 5.0 scale

  36 months

• Assessment of adverse events due to radiotherapy by using the NCI-CTCAE version 5.0

  36 months

• Collection of dosimetric results regarding dose/volume from the planned dosimetry, such as coverage of the planning targeted volume (PTV) by the prescription dose in the accumulated dose

  An average of 9 months after the beginning of treatment (chemotherapy then radiotherapy)

• Collection of dosimetric results regarding dose/volume from the planned dosimetry, such as dose received by the gross total volume

  An average of 9 months after the beginning of treatment (chemotherapy then radiotherapy)

• Collection and Summation of the dosimetric results in terms of dose/volume for the adaptive radiotherapy sessions and comparison with the predicted dosimetry

  An average of 9 months after the beginning of treatment (chemotherapy then radiotherapy)

Study Arms (1)

Gabrinox followed by stereotactic radiotherapy

EXPERIMENTAL

Gembrax: Albumin-bound paclitaxel followed by Gemcitabine Day 1,8,15 followed by 2 weeks of rest Folfirinox: Oxaliplatin, irinotecan, leucovorin, 5FU bolus and continuous

Combination Product: Gabrinox; Radiation: MRI-GUIDED STEREOTACTIC RADIOTHERAPY

Interventions

MRI-GUIDED STEREOTACTIC RADIOTHERAPY RADIATION

Radiotherapy will start between 5 and 6 weeks after the last injection of chemotherapy (FOLFIRINOX regimen) in non-progressive patients after Gabrinox. Stereotactic adaptive radiotherapy in five fractions: prescription dose in five fractions of 10 Gy/day on consecutive days. At least two sessions/week should be performed. An interval of at least 18 hours between fractions is recommended.

Gabrinox followed by stereotactic radiotherapy

Gabrinox COMBINATION_PRODUCT

Regimen: GEMBRAX Other Names: Albumin bound paclitaxel 125 mg/m² + Gemcitabine 1000 mg/m² Regimen: FOLFIRINOX Other Names: Oxaliplatin 85 mg/m² + Leucovorin 200 mg/m² + Irinotecan 180 mg/m² + 5FU bolus 400mg/m² + 5FU continuous 2400 mg/m² Gembrax + Folfirinox = GABRINOX

Gabrinox followed by stereotactic radiotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient aged from 18 to 75 years at the date of signature of the consent form
• Histologically or cytologically proven pancreatic adenocarcinoma
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Non-resectable tumour according to the National Comprehensive Cancer Network (NCCN) 1.2015 recommendations after external review of imaging data by multidisciplinary experts.
• Non-metastatic cancer confirmed by thorax-abdomen-pelvis computerized tomography (CT) scan and liver MRI
• SMART feasibility confirmed by centralized review
• Uracilemia \< 16 ng/ml
• Neutrophils ≥ 2 000/mm3 (2 × 109/L);
• Platelets ≥ 100 000/mm3 (100 × 109/L);
• Hemoglobin ≥ 9 g/dl
• 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 mg/L (≤34 μmol/L), and in the absence of cholangitis.
• 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).
• Serum calcium AND magnesium AND potassium ≥ Lower Limit Normal (LLN and ≤ 1.2 x Upper Limit Normal (ULN)
• 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.

You may not qualify if:

• Any previous treatment for pancreatic cancer (e.g. chemotherapy, radiotherapy, surgery, targeted therapy, experimental therapy)
• Gilbert's syndrome or homozygous Uridine DiPhosphate Glucuronosyl Transferase 1 A1 (UGT1A1 \* 28)
• Prior radiotherapy likely to overlap with the planned study radiotherapy area (e.g. previous abdominal irradiation).
• Patients with high cardiovascular risk, including, but not limited to, coronary stent or myocardial infarction in the past 6 months.
• Peripheral neuropathy ≥ grade 2
• ECG with QTcorrected (QTc) interval longer than 450 ms for men and longer than 470 ms for women
• Contraindication to MRI and MRI-guided radiotherapy
• History of chronic inflammatory disease of the colon or rectum
• 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)
• 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
• Legal incapacity (patient under guardianship or wardship)
• Active and uncontrolled bacterial or fungal infection that requires systemic treatment.
• Know active HIV infection
• History of peripheral arterial disease (e.g. lameness, Buerger's disease).
• Patient with history of pulmonary fibrosis or interstitial pneumonia.

Sponsors & Collaborators

• Institut du Cancer de Montpellier - Val d'Aurelle: lead

Study Sites (9)

Institut Paoli Calmettes

Marseille, Bouches-du-Rhône, 13009, France

RECRUITING

CHU Carémeau

Nîmes, Gard, 30029, France

RECRUITING

CHU Saint-Eloi

Montpellier, Herault, 34295, France

RECRUITING

Institut régional du Cancer de Montpellier

Montpellier, Hérault, 34298, France

RECRUITING

Hôpital Beaujon

Clichy, France

NOT YET RECRUITING

Centre Georges-François Leclerc

Dijon, 21079, France

RECRUITING

Hôpital Pitié Salpétriêre

Paris, 75013, France

RECRUITING

Centre Eugène Marquis

Rennes, 35042, France

NOT YET RECRUITING

Hopital Paul Brousse

Villejuif, France

NOT YET RECRUITING

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MeSH Terms

Conditions

Neoplasms

Study Officials

• Fabienne Portalès, MD

  Institut de Cancérologie de Montpellier (ICM)

  STUDY CHAIR

Central Study Contacts

Aurore MOUSSION, MD

CONTACT

0467612446; Aurore.Moussion@icm.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2020
• First Posted: September 30, 2020
• Study Start: June 16, 2021
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): June 1, 2030
• Last Updated: December 5, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Access to study data upon written detailed request sent to ICM, from 6 months until 5 years after publication of summary data.
• Access Criteria: The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from ICM for personal access, and data will only be transferred after signing of a data access agreement.

Locations

FR (9)