Clinical Trial Page

Summary
EudraCT Number:2004-000327-15
Sponsor's Protocol Code Number:XL119-001
National Competent Authority:Belgium - FPS Health-DGM
Clinical Trial Type:EEA CTA
Trial Status:Completed
Date on which this record was first entered in the EudraCT database:2005-12-20
Trial results View results
Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL
A. Protocol Information
A.1Member State ConcernedBelgium - FPS Health-DGM
A.2EudraCT number2004-000327-15
A.3Full title of the trial
A Phase 3 Multicenter, Open-label, Randomized Study of XL119 Versus 5-Fluorouracil (5-FU) plus Leucovorin (LV) in Subjects with Advanced Biliary Tumors Not Amenable to Conventional Surgery
A.3.2Name or abbreviated title of the trial where available
XL119 versus 5-FU/LV in Advanced Biliary Tumors
A.4.1Sponsor's protocol code numberXL119-001
A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorHelsinn Healthcare SA
B.1.3.4CountrySwitzerland
B.3.1 and B.3.2Status of the sponsorCommercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing support
B.4.2Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisation
B.5.2Functional name of contact point
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation No
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameBecatecarin
D.3.2Product code XL119
D.3.4Pharmaceutical form Solution for infusion
D.3.4.1Specific paediatric formulation Information not present in EudraCT
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNBecatecarin
D.3.9.1CAS number 119673-08-4
D.3.9.2Current sponsor codeXL119
D.3.9.3Other descriptive nameDEAE-rebeccamycin, NSC 655649, BMY-27557, BMS181176, rebeccamycin analog
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number10
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Information not present in EudraCT
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 2
D.1.2 and D.1.3IMP RoleComparator
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Fluorouracil 25 mg/ml
D.2.1.1.2Name of the Marketing Authorisation holderMayne Pharma Plc (previously Faulding Pharmaceuticals Plc)
D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameFluorouracil BP
D.3.4Pharmaceutical form Solution for injection
D.3.4.1Specific paediatric formulation Information not present in EudraCT
D.3.7Routes of administration for this IMPIntravenous bolus use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNFluorouracil
D.3.9.1CAS number 51218
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number25 and 50
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Information not present in EudraCT
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 3
D.1.2 and D.1.3IMP RoleComparator
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Calcium Leucovorin 10 mg/ml injection
D.2.1.1.2Name of the Marketing Authorisation holderMayne Pharma Plc (previously Faulding Pharmaceuticals Plc)
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameCalcium Leucovorin
D.3.4Pharmaceutical form Solution for injection
D.3.4.1Specific paediatric formulation Information not present in EudraCT
D.3.7Routes of administration for this IMPIntravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNCalcium Leucovorin
D.3.9.1CAS number 1492188
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number10
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Information not present in EudraCT
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.IMP: 4
D.1.2 and D.1.3IMP RoleComparator
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Fluorouracil 50 mg/ml
D.2.1.1.2Name of the Marketing Authorisation holderMayne Pharma Plc (previously Faulding Pharmaceuticals Plc)
D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameFluorouracil BP
D.3.4Pharmaceutical form Solution for injection
D.3.4.1Specific paediatric formulation Information not present in EudraCT
D.3.7Routes of administration for this IMPIntravenous bolus use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNFluorouracil
D.3.9.1CAS number 51218
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number25 and 50
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin Yes
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Information not present in EudraCT
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Advanced Biliary Tract Tumours: Gall bladder cancer and Cholangiocarcinoma
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 7.0
E.1.2Level LLT
E.1.2Classification code 10028982
E.1.3Condition being studied is a rare disease Yes
E.2 Objective of the trial
E.2.1Main objective of the trial
To compare overall survival duration for XL119 and 5FU/LV treated subjects
E.2.2Secondary objectives of the trial
1) To determine progression free survival for XL119 and 5FU/LV treated subjects (clinical or radiologic (radiographic only for tumors assessed as measurable at baseline).
2) To evaluate clinical benefit for XL119 and 5FU/LV treated subjects using ECOG Performance Status and FACT-Hep Quality of Life subscales. An additional measure of efficacy in subjects with measurable disease will be best tumor response. Determination of best-tumor response will be based on objective tumor assessments made according to the Response Evaluation Criteria in Solid Tumors (RECIST) system of unidimensional evaluation.
3) To assess the safety profile of XL119 : (1) serious and nonserious AEs and (2) laboratory evaluations. An Independent Data Monitoring Committee (IDMC) will periodically review serious adverse events, abnormal laboratory tests, futility, and efficacy at two interim analysis meetings. Two interim analyses will be performed after 33% and 50% of the total deaths (516) are reported.
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
Inclusion Criteria
•Male and female subjects with advanced histologically confirmed biliary cancer (gallbladder cancer or cholangiocarcinoma) that is not amenable to conventional surgical approach. If only cytology is available, written approval by medical monitor is required.
•18 years or older
•Life expectancy of at least 12 weeks
•Eastern Cooperative Oncology Group (ECOG) Performance Status score <3
•Laboratory criteria (within 72 hours of first XL119 treatment): white blood cell count (WBC) >3000/µL, absolute neutrophil count ≥1500/µL; hemoglobin ≥9.5 g/dL; platelet count ≥100,000/µL, lymphocyte count <20,000/µL; , serum creatinine within ULN; if > ULN, creatinine clearance ≥ 60 ml/min; alanine transaminase (ALT) and aspartate transaminase (AST) within 2.5 times the upper limit of normal; bilirubin <3 mg/dL
•Willing and able to sign informed consent
•Sexually active men and women must use an accepted and effective method of contraception (including barrier contraception with spermicide)
•Women of child-bearing age must have a negative pregnancy test
E.4Principal exclusion criteria
Main exclusion criteria:·
•Prior chemotherapy (excluding chemotherapy given as adjuvant treatment completing more than 6 months prior to entry into study)
•Unstable angina, or class III or IV New York Heart Association heart disease
•Central nervous system metastases
•Uncontrolled diabetes mellitus
•Uncontrolled seizure disorder
•Major surgery, immunotherapy, biological therapy, or radiotherapy during the 28 days preceding the first study treatment
•Need for concomitant anticancer therapy (chemotherapy, immunotherapy, biological therapy or radiation) or other investigational agents during study participation or 28 days prior to study participation
•Pregnant or breast-feeding
•A known history of human immunodeficiency virus (HIV) infection
E.5 End points
E.5.1Primary end point(s)
The primary efficacy variable will be obtained by determining the overall survival duration, as either, alive, dead, or lost to follow up, at each study visit, at the termination date, and at regular intervals following termination from the study visit, at the termination date.
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic No
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) No
E.7.3Therapeutic confirmatory (Phase III) Yes
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised Yes
E.8.1.2Open Yes
E.8.1.3Single blind No
E.8.1.4Double blind No
E.8.1.5Parallel group No
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) Yes
E.8.2.2Placebo No
E.8.2.3Other Yes
E.8.2.3.1Comparator description
Fluorouracil and Leucovorin
E.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned1
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA43
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
E.8.7Trial has a data monitoring committee Yes
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
Assuming the trial goes to full enrollment and that neither the first nor second interim analysis demonstrates either efficacy or futility, the final analysis would occur after 512 subjects have died. Based on historical data for the population being studied, it is estimated this would occur approximately 6 months following enrollment of the six hundredth subject.
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years4
E.8.9.1In the Member State concerned months0
E.8.9.1In the Member State concerned days0
E.8.9.2In all countries concerned by the trial years4
E.8.9.2In all countries concerned by the trial months0
E.8.9.2In all countries concerned by the trial days0
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero Information not present in EudraCT
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
F.1.1.3Newborns (0-27 days) Information not present in EudraCT
F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
F.1.1.5Children (2-11years) Information not present in EudraCT
F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
F.1.2Adults (18-64 years) Yes
F.1.3Elderly (>=65 years) Yes
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state25
F.4.2 For a multinational trial
F.4.2.1In the EEA 300
F.4.2.2In the whole clinical trial 600
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
Subjects may receive up to 12 cycles of treatment (approximately 12 months of treatment for a total of up to 60 infusions). If after 12 cycles of treatment, in the opinion of the investigator, the subject has not progressed, he or she should continue with the current treatment up to progression
G. Investigator Networks to be involved in the Trial
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2005-01-26
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2005-01-25
P. End of Trial
P.End of Trial StatusCompleted

Sponsors and Collaborators

Medical Conditions

Drug Interventions

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