Safety and Efficacy of Modified Folfirinox Versus Gemcis in Bile Duct Tumours

Learn more about:
Related Clinical Trial
Recurrence After Whipple’s (RAW): Retrospective Cohort Study Investigating Patterns of Cancer Recurrence Following Pancreaticoduodenectomy for Pancreatic Head Malignancy Implementing Acupuncture and Chinese Herbal Medicine Into Palliative Care Prospective Evaluation of Biliary Tissue Sampling With ERCP Combination of Trametinib (MEK Inhibitor) and Hydroxychloroquine (HCQ) (Autophagy Inhibitor) in Patients With KRAS Mutation Refractory Bile Tract Carcinoma (BTC). DNA Methylation Biomarker for Diagnosis of Cholangiocarcinoma in Patients With Bile Duct Stricture Liver Cancer Registry Platform Target Rare Cancer Knowledge Neoadjuvant Therapy in Biliary Adenocarcinoma BOLD-100 in Combination With FOLFOX for the Treatment of Advanced, Solid Tumours the Impact of Early Palliative Care on the Survival of Locally Advanced and / or Metastatic Cholangiocarcinoma Patients Nutritional Preferences and Product Accessibility in Oral Nutritional Supplements in Participants With Breast, Colorectal, Upper Gastrointestinal, or Prostate Cancer High Volume Washing of the Abdomen in Increasing Survival After Surgery in Patients With Pancreatic Cancer That Can Be Removed by Surgery Short-term Starvation vs. Normal Diet Before Chemotherapy of Solid Tumors Evaluation of MRI Sequences for Ultra-rapid Acquisition of Bile Ducts Images Study of Oral Ceritinib in Patients With ALK and ROS1 Activated Gastrointestinal Malignancies Obtaining Solid Tumor Tissue From People Having Biopsy or Surgery for Certain Types of Cancer Improving Outcomes in Cancer Patients With a Nutritional and Physical Conditioning Prehabilitation Program 18F-FSPG PET in Imaging Patients With Liver Cancer Before Undergoing Surgery or Transplant A Clinical Trial to Evaluate Safety and Efficacy of Endovascualr Denervation in Treatment of Cancer Pain Comparison Between Internal and External Preoperative Biliary Drainage in Periampullary Cancers A Study of TRK-950 in Combinations With Anti-Cancer Treatment Regimens in Patients With Advanced Solid Tumors Anesthetic Agents and Acute Kidney Injury After Liver Resection Surgery Efficacy of Fistulotomy for Biliary Cannulation A Study of LY3039478 in Participants With Advanced or Metastatic Solid Tumors Etomidate vs. Midazolam for Sedation During ERCP Loop-tipped Guidewire in Selective Biliary Cannulation Pancreatic Head and Peri-ampullary Cancer Laparoscopic vs Open Surgical Treatment Trial (PLOT) Effects of OXY111A in Primary and Secondary Hepato-Pancreato-Biliary Neoplasm BKM120 in Cancers With PIK3CA Activating Mutations A First-in-human Phase Ia/b, Open Label, Multicentre, Dose Escalation Study of BI 905711 in Patients With Advanced Gastrointestinal Cancers Infigratinib for the Treatment of Advanced or Metastatic Solid Tumors in Patients With FGFR Gene Mutations Changes in Liver Function After Stereotactic Body Radiation Therapy Measured by PET/CT PTFE Stents for Treatment of Malignant Biliary Strictures Irreversible Electroporation of Unresectable Liver Tumors Personal Resilience Empowerment Program Study Radiofrequency Ablation for Biliopancreatic Malignancy Early Enteral Feeding After Pylorus Preserving Pancreatoduodenectomy Influence of an Oral Nutritional Supplement Rich in Omega-3 Fatty Acids on Functional State and Quality of Life in Malnourished Patients With Gastroenterological Tumors National Translational Science Network of Precision-based Immunotherapy for Primary Liver Cancer In Vitro Models of Liver and Pancreatic Cancer Biliary Tissue Sampling Using a Cytology Brush or the GIUM Catheter Evaluation of Stereotactic Radiosurgery For Liver Malignancies Beacon BNX™ Endoscopic Ultrasound (EUS)-Needle vs SharkCore™ Needle A Pilot Study to Assess Theragnostically Planned Liver Radiation With Functional DVH Analysis to Optimize Individualized Radiation Therapy Radiofrequency Ablation Using Octopus Electrodes for Treatment of Focal Liver Malignancies Accuracy of Endoscopic Ultrasound for Detection of Tumors of the Liver Prospective Study of the Risk of Bacteremia in Directed Cholangioscopic Examination of the CBD Margin Status After Pancreaticoduodenectomy for Cancer A Pilot Study of Combined Immune Checkpoint Inhibition in Combination With Ablative Therapies in Subjects With Hepatocellular Carcinoma (HCC) or Biliary Tract Carcinomas (BTC) Study of Olaparib and Durvalumab in IDH-Mutated Solid Tumors Comparison Bile Duct Brushings, Cholangioscopy-Directed Biopsies and Pediatric Forceps Biopsies in Biliary Strictures Effects of Preoperative Immunonutrition in Patients Undergoing Pancreaticoduodenectomy A Study of BBI503 in Adult Patients With Advanced Hepatobiliary Cancer A Study of TRK-950 in Patients With Advanced Solid Tumors Combined HCC-MFCCC Proton Therapy and Bevacizumab for Primary Liver Tumors Effects of Preoperative Immunonutrition in Patients Undergoing Hepatectomy Proton Beam Irradiation for the Treatment of Unresectable Hepatocellular Cancer or Hepatic Metastases Fluorescence QRH-882260 Peptide Imaging in the Bile Duct A Phase 1 Study of ZSP1241 in Participants With Advanced Solid Tumors pCLE For the Diagnosis Of Cancer in Unknown Bile Duct Stricture Unilateral Versus Bilateral Stents for Bismuth Type II and III Malignant Hilar Strictures Yttrium-90 Radioembolization Using Glass Microspheres (TheraSphere) for Patients With Liver Metastases Olaparib in Treating Patients With Advanced Glioma, Cholangiocarcinoma, or Solid Tumors With IDH1 or IDH2 Mutations Study of Sildenafil as a Therapy for Fatigue in Pancreatic Cancer Study of Gemcitabine With TheraSphere® (Yttrium-90)in Patients With Hepatic Tumors of Pancreatobiliary Origin Radiation Therapy in Treating Patients With Hepatocellular Carcinoma, Cholangiocarcinoma, or Liver Metastasis Who Have Impaired Liver Function Phase 1 In-vivo Biliary Study of KSP/QRH Heptapeptide Dimer MRCP Diagnoses EHCC Better When Combined DWI Safety and Efficacy of Modified Folfirinox Versus Gemcis in Bile Duct Tumours Comparison of Biliary Forceps Biopsy and Brush Cytology Perioperative MVT-5873, a Fully Human Monoclonal Antibody Against a CA 19-9 Epitope, for Operable CA 19-9 Producing Pancreatic Cancers, Cholangiocarcinomas, and Metastatic Colorectal Cancers Pilot Study of Irreversible Electroporation (IRE) to Treat Metastatic Liver Cancer & Cholangiocarcinoma Endoscopic Bipolar Radiofrequency Probe (ENDOHPB) in the Management of Unresectable Bile Duct and Pancreatic Cancer A Registry of Patients Undergoing Cellvizio Endomicroscopy and Endoscopic Retrograde Cholangiopancreatography(ERCP) Imaging Procedures for Diagnosing Pancreatic and Bile Duct Cancers Cyclooxygenase-2 Inhibitor for Adjuvant Anticancer Effect in Patients With Biliary-pancreas Cancer Endobiliary RFA for Unresectable Malignant Biliary Strictures A Clinical Trial of Entinostat in Combination With Nivolumab for Patients With Previously Treated Unresectable or Metastatic Cholangiocarcinoma and Pancreatic Adenocarcinoma Clinical Effect and Safety of PDT and RFA for Unresectable EHCC Safety and Efficiency of Photodynamic Therapy for Blie Duct Carcinoma Gemcitabine With Peptide Vaccine Therapy in Treating Patients With Bile Duct Cancer A Study of the Use of the Medtronic Pump and Codman Catheter to Give Chemotherapy to Patients With Colorectal Carcinoma or Cholangiocarcinoma Trial of IRE in Cholangiocarcinoma Intra-hepatic Chemotherapy in Patient With Non-resectable Liver Metastases From Cholangiocarcinoma Chemo Alone or in Combination With Radiation in Unresectable Cholangiocarcinoma ASLAN001 in Patients With Advanced or Metastatic Cholangiocarcinoma Who Progressed on at Least 1 Line of Systemic Therapy A Study of Gemcitabine as an Adjuvant Treatment for Cholangiocarcinoma After Surgical Resection Efficiency Evaluation of Photodynamic Therapy With Photofrin® on Unresectable Type III or IV Cholangiocarcinomas PCI Treatment/Gemcitabine & Chemotherapy vs Chemotherapy Alone in Patients With Inoperable Extrahepatic Bile Duct Cancer S-1 in Combination With Abraxane in Treating Cholangiocarcinoma Phase II Trial of Nab-Paclitaxel and Gemcitabine for First-Line Treatment of Patients With Cholangiocarcinoma Combination Chemotherapy Plus Panitumumab or Bevacizumab for Inoperable Cholangiocarcinoma Without KRAS Mutations A Phase I/II Safety and Efficacy Study of PCI of Gemcitabine and Chemotherapy in Patients With Cholangiocarcinomas Comparison of Endoscopic Radiofrequency Ablation Versus Photodynamic Therapy for Inoperable Cholangiocarcinoma Diagnosis, Treatment Status and Prognosis of Cholangiocarcinoma in China: a Multicenter, Two-way, Non-intervention Study Gemcitabine/Oxaliplatin and Photodynamic Therapy in Cholangiocarcinoma Efficacy and Safety of Pemigatinib in Subjects With Advanced/Metastatic or Surgically Unresectable Cholangiocarcinoma Who Failed Previous Therapy – (FIGHT-202) Pemigatinib in Treating Patients With Advanced/Metastatic or Surgically Unresectable Cholangiocarcinoma Including FGFR2 Rearrangement Radiofrquency Ablation Combined With Cytokine-induced Killer Cells for the Patients With Cholangiocarcinoma Chart Review: Unresectable/Metastatic Cholangiocarcinoma Treated With Irinotecan, Capecitabine and Celecoxib Study of TRIFLURIDINE/TIPIRACIL in Previously Treated Cholangiocarcinoma Study Of Intrahepatic Arterial Injection of 90-Y Glass Microspheres for Cholangiocarcinoma Combined Biological Treatment and Chemotherapy for Patients With Inoperable Cholangiocarcinoma Neoadjuvant mFOLFOXIRI for Potentially Resectable Cholangiocarcinoma Gemcitabine, Oxaliplatin and Capecitabine in Patients With Advanced Cholangiocarcinoma Registry Study of Neoadjuvant Chemoradiation & Transplant for Cholangiocarcinoma Patients Study of RAD001 in Advanced Cholangiocarcinoma: RADiChol Study of Pembrolizumab and Olaparib in Bile Duct Cancer Cohort of Patients With Hepatocellular Carcinoma or Cholangiocarcinoma Second Line Chemotherapy FOLFIRINOX in Irresectable Cholangiocarcinoma ncRNAs in Exosomes of Cholangiocarcinoma Single Arm Study of RAD001 as Monotherapy in Treatment in Advanced Cholangiocarcinoma Trial of Therapeutic Vaccine in Patients With Cholangiocarcinoma

Brief Title

Safety and Efficacy of Modified Folfirinox Versus Gemcis in Bile Duct Tumours

Official Title

Randomised Phase II/III Study, Assessing the Safety and Efficacy of Modified Folfirinox Versus Gemcis in Locally Advanced, Unresectable and/or Metastatic Bile Duct Tumours

Brief Summary

      Bile duct tumours are rare. They are the 6th most common type of digestive cancer. Their
      therapeutic management is complex and must be multidisciplinary in nature. Most of the time,
      an endoscopic or radiological biliary drainage is necessary before any tumour treatment.

      Their prognosis is poor due to the fact that they are normally diagnosed late, which makes
      curative surgery impossible. A population study in the Côte d'Or region of France reported a
      survival rate at 5 years of approximately 10%.

      For the locally advanced or metastatic forms, treatment has not been properly codified. With
      respect to chemotherapy, prospective studies, most often phase II, are difficult to interpret
      due to a limited number of patients and due to the heterogeneity of this type of tumour (bile
      duct and pancreas tumours). Treatment with 5FU alone provides an objective response in
      approximately 10% of cases. In combination with mitomycin or carboplatin, the objective
      response rate is 20%, with a median survival period of 5 months. Interferon combined with 5FU
      has a better response rate (30%), but occurrences of different types of toxicity are more
      frequent.

      More recently, gemcitabine and the 5FU-cisplatin combinations demonstrated objective tumour
      control in 50% of patients with a median survival period of 10 months. Gemcitabine combined
      with oxiplatin or with cisplatin has shown the same response rate but a median survival
      period of approximately 12 months.

      The benefit of this combination has been confirmed in a phase III trial that compared the
      gemcitabine-cisplatin combination to gemcitabine alone, in 410 patients with locally advanced
      unresectable and/or metastatic bile duct cancer. The results were in favour of the combined
      treatment with a median survival period of 11.7 months (versus 8.1 months - HR 0.64 [0.52 -
      0.80]). This combination is currently the reference first-line treatment.
    

Detailed Description

      At the same time as these results, triple therapies involving 5FU + oxiplatin + irinotecan
      have objectively shown a significant increase in overall survival of patients with metastatic
      pancreatic adenocarcinoma compared to gemcitabine alone (median of 11.1 months versus 6.8
      months, HR = 0.57 [0.45 - 0.73] p < 0.0001). The response rate and progression-free survival
      (PFS) have also been improved with these triple therapies; the response rates were 31.6%
      versus 9.4% p < 0.001 and the median PFS 6.4 months versus 3.3 months p < 0.001,
      respectively.

      The adverse events observed with the triple therapy occurred more frequently, for febrile
      neutropaenia (5.4%), with the need to treat with growth factors (G-CSF for 42.5% of
      patients). Haematological and digestive toxicity was also higher: grade 3-4 neutropaenia was
      observed for 45.7% of patients in the FOLFIRINOX arm and 18.7% of patients in the gemcitabine
      arm (p = 0.0001); vomiting was noted for 14.5% of patients in the FOLFIRINOX arm and 4.7% in
      the gemcitabine arm (p = 0.002). Quality of life was improved in the FOLFIRINOX arm.

      Due to the histological, therapeutic and prognostic similarities between pancreatic and bile
      duct cancer, it is interesting to assess this triple therapy compared to the current
      reference treatment in bile duct cancers: gemcitabine combined with cisplatin (GEMCIS). Due
      to the known higher levels of toxicity for this triple therapy (digestive and
      haematological), the investigators modified the conventional FOLFIRINOX regimen (mFOLFIRINOX)
      by removing the 5-FU bolus at D1 of each cycle. This modification to the regimen would appear
      not to decrease the efficacy of the treatment.
    

Study Phase

Phase 2/Phase 3

Study Type

Interventional


Primary Outcome

percentage of patients who are alive without radiological progession

Secondary Outcome

 overall survival

Condition

Bile Duct Cancer

Intervention

GEMCIS

Study Arms / Comparison Groups

 GEMCIS
Description:  

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

316

Start Date

December 15, 2015

Completion Date

September 2023

Primary Completion Date

September 2023

Eligibility Criteria

        Inclusion Criteria:

          -  - WHO 0 or 1

          -  Age ≥ 18 years

          -  Tumour of the intrahepatic or extrahepatic (and/or hilar) bile ducts, or of the
             gallbladder

          -  Measurable abdominal metastases (at least a lesion >10 mm) and/or measurable,
             unresectable primary tumour

          -  Disease proven by histopathology or cytology (on metastasis or primary tumour)

          -  If there are no abdominal metastases, the unresectability must be confirmed by a
             hepatobiliary surgeon in a multidisciplinary team (MDT) meeting

          -  Bilirubin <1.5 N (after endoscopic or trance hepatic optimum biliary drainage, if
             necessary), AST and ALT <10N

          -  Serum creatinine <130 µmol/L, creatinine clearance >60 mL/min

          -  Neutrophils ≥ 1500/mm3 and platelets ≥ 75,000/mm3

          -  Prothrombin index > 70%

          -  Serum albumin > 25 g/L

          -  Patient registered with a social security scheme (including CMU)

          -  Signed informed consent form

        Exclusion Criteria:

          -  - Non-measurable metastases and primary tumour

          -  Ampullary carcinoma or cancer of the pancreas with infiltration of the bile ducts or
             mixed tumours (hepatocholangiocarcinoma)

          -  Chemotherapy and/or radiotherapy within the last 4 months

          -  Other malignant tumour except in situ basal cell carcinoma or curatively treated
             carcinoma of the uterine cervix or other malignant tumour that has been treated and
             has been considered cured for at least 5 years

          -  Major comorbidity factors (unstable angina, myocardial infarction that has occurred
             within the last 6 months, heart failure ≥2 according to the NYHA classification,
             uncontrolled high blood pressure)

          -  Woman who is pregnant or breastfeeding, or patient of either sex who is of
             childbearing age and not using an adequate contraceptive method

          -  Not able to undergo the trial medical follow-up for geographical, social or
             psychological reasons.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Jean-Marc Phelip, PhD, (0)477828320, [email protected]

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT02591030

Organization ID

1408212

Secondary IDs

2015-002282-35

Responsible Party

Sponsor

Study Sponsor

Centre Hospitalier Universitaire de Saint Etienne

Collaborators

 Federation Francophone de Cancerologie Digestive

Study Sponsor

Jean-Marc Phelip, PhD, Principal Investigator, CHU Saint-Etienne


Verification Date

January 2020