advanced Biliary Tract Cancer MedDRA version: 17.0 Level: PT Classification code 10055111 Term: Biliary cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: STIVARGA
Pharmaceutical Form: Coated tablet
Trade Name: GEMCITABINE
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: GEMCITABINE
CAS Number: 95058-81-4
Concentra
Sponsors
Institut régional du Cancer - Montpellier - Val d'Aurelle
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adenocarcinoma of the biliary tract (gallbladder, intra and/or extrahepatic bile ducts, or ampulla of Vater): Cytologically or histologically proven adenocarcinoma of the biliary tract. In case of uncertain biliary tract origin (e.g., intrahepatic, peripheral cholangiocarcinomas), inclusion is possible if i) extensive search for primary origin (thoracic and abdominopelvic Computed Tomography scanner (CT scan), upper digestive endoscopy) is negative; and ii) histological examination is consistent with bile duct adenocarcinoma (ImmunoHistoChemistry (IHC) should ideally be performed and be consistent with biliary primary disease, e.g., positive for cytokeratin 7 and negative for cytokeratin 20). 2. Metastatic disease with no curative surgery option or metastatic recurrence after resection. 3. At least one measurable lesion in a non-irradiated area according to Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). 4. No biliary obstruction. 5. Age between 18 and 75 years. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Life expectancy higher than 3 months. 8. No prior chemotherapy for advanced disease. Previous adjuvant chemotherapy including Gemcitabine and/or platinum based is allowed if completed at least 6 months previously and relapsing after completion of the last dose. 9. Total bilirubin = 2.5 times the upper limit of the normal range (ULN). Patients with jaundice or evidence of bile duct obstruction, in whom the biliary tree can be decompressed by endoscopic or percutaneous endoprothesis (at least 15 days before inclusion) with subsequent reduction in total bilirubin = 3 ULN, will be eligible for the study. 10. Aminotransferases (AST, ALT) = 2.5 ULN (= 5 ULN in case of diffuse hepatic involvement), INR 50 mL/min/1.73m² according to the Modification of Diet in Renal Disease (MDRD) formula, neutrophils = 1.5.10^9/L, platelets = 100.10^9/L, hemoglobin = 9 g/dL (red blood cell transfusion is allowed if needed). 11.Signed informed consent obtained before any study specific procedures. 12.Patients must be affiliated to a Social Security System. 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 44 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 43
Exclusion criteria
Exclusion criteria: 1. Known central nervous system metastases. 2. Known history of human immunodeficiency virus (HIV) infection 3. Contraindication or history of allergic reaction to one of the treatment components. 4. Previous irradiation (external radiotherapy or brachytherapy) within 30 days prior to study treatment. 5. Major surgery within 30 days prior to study treatment. 6. Participation in another clinical trial within 30 days prior to study treatment. 7. Concomitant systemic immunotherapy, chemotherapy, antitumor hormone therapy, targeted therapy or any experimental therapy. 8. Active uncontrolled infection, peripheral neuropathy grade = 2, acute or subacute bowel obstruction, history of inflammatory bowel disease, interstitial pneumonitis, respiratory failure, renal failure, dysphagia or any malabsorption condition. 9. Symptomatic coronary heart disease or myocardial infarction in the past 6 months, congestive heart failure (NYHA class II), prior cerebrovascular accident. 10.Uncontrolled hypertension (systolic blood pressure (BP) > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management). 11.Proteinuria of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) = grade 2 (i.e. urinary protein = 1.0 g/24 hrs). 12.Patients with current or anticipated need for strong Cytochrome P450 3A4 (CYP3A4) inhibitors or inducers. 13.Pregnancy (or positive ß-HCG dosage at inclusion), breast-feeding, or lack of effective contraception in male or female patients of reproductive potential. 14.Other malignancies either currently active or in the last 5 years, except adequately treated in situ carcinoma of the cervix and basal or squamous cell skin carcinoma. 15.Legal incapacity or physical, psychological or mental status interfering with the patient's ability to sign the informed consent or to terminate the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: For Phase 1b: The main objective for this dual-center open-label phase Ib study is to determine the RD for the phase II trial of Regorafenib administered in combination with mGEMOX in patients with advanced biliary tract cancer. For phase 2 : Evaluating the treatment efficacy of the recommended dose of Regorafenib and mGEMOX by assessing the progression free survival according RECIST criteria (version 1.1).;Secondary Objective: To evaluate Objective Response, To evaluate the duration of overall response (complete or partial) according RECIST criteria (version 1.1), To evaluate the non-progression rate (OR+SD) according RECIST criteria (version 1.1), To evaluate the feasibility and safety profile of the combination of mGEMOX and Regorafenib according to the NCI-CTCAE, version 4.03, To evaluate the overall survival.;Primary end point(s): For phase 1b : Limiting Toxicities during and within 6 weeks (2 cycles) after the beginning of the treatment. DLT definition. For phase 2 : Progression-free survival (according RECIST v1.1).;Timepoint(s) of evaluation of this end point: Not applicable | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): For phase 2 : • Objective response (OR) rate • Disease control rate • Safety profile (assessed by CTCAE v 4.03) • Overall survival (OS);Timepoint(s) of evaluation of this end point: Not applicable | — |
Countries
France
Contacts
Public ContactJean Pierre BLEUSE
Institut régional du Cancer - Montpellier - Val d'Aurelle
Outcome results
None listed