Clinical Trial Page

Summary
EudraCT Number:2020-001001-22
Sponsor's Protocol Code Number:D910SC00001
National Competent Authority:Poland - Office for Medicinal Products
Clinical Trial Type:EEA CTA
Trial Status:Ongoing
Date on which this record was first entered in the EudraCT database:2020-12-10
Trial 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 ConcernedPoland - Office for Medicinal Products
A.2EudraCT number2020-001001-22
A.3Full title of the trial
A Phase III, Randomized, Double-Blind, Placebo Controlled, Multi-Center, International Study of Durvalumab Given Concurrently With Definitive Chemoradiation Therapy in Patients With Locally Advanced, Unresectable Esophageal Squamous Cell Carcinoma (KUNLUN)
NOTE: Official Title should have no more than 240 characters
Randomizowane, wieloośrodkowe, międzynarodowe badanie fazy III prowadzone metodą podwójnie ślepej próby z kontrolą placebo, oceniające durwalumab podawany jednoczasowo z chemioradioterapią radykalną u pacjentów z miejscowo zaawansowanym, nieoperacyjnym płaskonabłonkowym rakiem przełyku (KUNLUN)
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
Study of Durvalumab Versus Placebo in Combination With Definitive Chemoradiation Therapy in Patient With locally advanced, unresctable ESCC
Badanie oceniające durwalumab podawany w połaczeniu z chemioradioterapią radykalną u pacjentów z miejscowo zaawansowanym, nieoperacyjnym płaskonabłonkowym rakiem przełyku
A.3.2Name or abbreviated title of the trial where available
KUNLUN
KUNLUN
A.4.1Sponsor's protocol code numberD910SC00001
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorAstraZeneca AB
B.1.3.4CountrySweden
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 supportAstraZeneca AB
B.4.2CountrySweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationAstraZeneca
B.5.2Functional name of contact pointClinical Study Information Center
B.5.3 Address:
B.5.3.1Street Address1800 Concorde Pike
B.5.3.2Town/ cityWilmington
B.5.3.3Post codeDE 19803
B.5.3.4CountryUnited States
B.5.6E-mailinformation.center@astrazeneca.com
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 nameDurvalumab
D.3.2Product code MEDI4736
D.3.4Pharmaceutical form Concentrate for solution for infusion
D.3.4.1Specific paediatric formulation No
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 INNdurvalumab
D.3.9.1CAS number 1428935-60-7
D.3.9.2Current sponsor codeMEDI4736
D.3.10 Strength
D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number50
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
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 No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
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 Yes
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 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 Yes
D.2.1.2Country which granted the Marketing AuthorisationPoland
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 nameCisplatin
D.3.4Pharmaceutical form Concentrate for solution for infusion
D.3.4.1Specific paediatric formulation No
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 INNcisplatin
D.3.9.1CAS number 15663-27-1
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) No
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 No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
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 No
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 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 Yes
D.2.1.2Country which granted the Marketing AuthorisationPoland
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 namecapecitabine
D.3.4Pharmaceutical form Film-coated tablet
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPOral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNcapecitabine
D.3.9.1CAS number 154361-50-9
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) No
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 No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
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 No
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 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 Yes
D.2.1.2Country which granted the Marketing AuthorisationPoland
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 name5-fluorouracil
D.3.4Pharmaceutical form Solution for infusion
D.3.4.1Specific paediatric formulation No
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 INN5-fluorouracil
D.3.9.1CAS number 51-21-8
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) No
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 No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
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 No
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
D.8 Placebo: 1
D.8.1Is a Placebo used in this Trial?Yes
D.8.3Pharmaceutical form of the placeboConcentrate for solution for infusion
D.8.4Route of administration of the placeboIntravenous use
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma
Miejscowo zaawansowany, nieoperacyjny płaskonabłonkowym rakiem przełyku
E.1.1.1Medical condition in easily understood language
Specific type of Esophageal cancer called "Esophageal Squamous Cell Carcinoma" (ESCC) that cannot be removed by surgery
Specyficzny typ raka przełyku zwany „Rakiem płaskonabłonkowym przełyku” (ESCC), którego nie można usunąć chirurgicznie
E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 21.0
E.1.2Level LLT
E.1.2Classification code 10015366
E.1.2Term Esophageal carcinoma
E.1.2System Organ Class 100000004864
E.1.3Condition being studied is a rare disease No
E.2 Objective of the trial
E.2.1Main objective of the trial
To assess the efficacy of durvalumab + dCRT compared with placebo + dCRT in all randomized patients and in patients with PD-L1 High tumors in terms of PFS using BICR assessments according to RECIST 1.1
Ocena skuteczności durwalumabu + chemioradioterapii radykalnej (dCRT) w porównaniu do placebo + dCRT u wszystkich zrandomizowanych pacjentów i u pacjentów z guzami z wysoką ekspresją PD-L1 pod względem przeżycia wolnego od progresji choroby (PFS) wg kryteriów RECIST 1.1, zgodnie z oceną BICR)
E.2.2Secondary objectives of the trial
- To assess the efficacy of durvalumab + dCRT compared to placebo + dCRT in all randomized patients and in patients with PD-L1 High tumors in terms of OS, APF24, ORR, DoR, DCR, TTP, PFS2, and OS36
- To assess patient-reported symptoms, functioning, and HRQoL in patients treated with durvalumab + dCRT compared to placebo + dCRT using patient reported outcome measures
- To assess the PK of durvalumab when in combination with dCRT in all randomized patients and in patients with PD-L1 High tumors
- To investigate the immunogenicity of durvalumab and durvalumab in combination with dCRT in all randomized patients and in patients with PD-L1 High tumors
1.Ocena skuteczności durwalumabu+dCRT w porównaniu do placebo + dCRT na podstawie całkowitego przeżycia (OS), odsetka pacjentów żyjących i wolnych od progresji choroby po 24 miesiącach od randomizacji (APF24), wskaźnika odpowiedzi obiektywnej (ORR), czasu trwania odpowiedzi (DoR), wskaźnika kontroli choroby (DCR), czasu do progresji choroby (TTP), czasu od randomizacji do drugiej progresji choroby (PFS2) i odsetka pacjentów żyjących po 36 miesiącach od randomizacji (OS36);
2.Ocena objawów zgłaszanych przez pacjenta, funkcjonowania i jakości życia związanej ze zdrowiem (HRQoL) u pacjentów leczonych durwalumabem + dCRT w porównaniu do placebo+dCRT na podstawie kwestionariuszy PRO
3.Ocena farmakokinetyki (PK) durwalumabu w skojarzeniu z dCRT u wszystkich zrandomizowanych pacjentów i u pacjentów z guzami z wysoką ekspresją PD-L1
4.Ocena immunogenności durwalumabu i urwalumabu w skojarzeniu z dCRT u wszystkich zrandomizowanych pacjentów i u pacjentów z guzami z wysoką ekspresją PD-L1
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
• 18 years or older at the time of signing the ICF.
• Histologically or cytologically confirmed esophageal squamous cell
carcinoma, and present with locally advanced disease (Stage II-IVA).
• Unresectable or refusing surgery, and has been deemed suitable for
definitive chemoradiation therapy.
• Patients with at least an evaluable lesion per RECIST 1.1
• Mandatory provision of available tumor tissue for PD-L1 expression
analysis.
• ECOG PS 0 or 1.
• Adequate organ and marrow function.
• Life expectancy of more than 3 months.
1. Co najmniej 18 lat w czasie składania podpisu na formularzu świadomej zgody.
2. Histologicznie lub cytologicznie potwierdzony płaskonabłonkowy rak przełyku, lokalnie zaawansowany (stadium od II do IVA).
3. Pacjenci z nowotworem określonym jako nieoperacyjny lub niewyrażający zgody na zabieg, kwalifikujący się do dCRT (chemioradioterapia radykalna).
4. Pacjenci z co najmniej 1 zmianą możliwą do ceny wg kryteriów RECIST 1.1.
5. Wszyscy pacjenci muszą przekazać próbkę guza w celu analizy ekspresji PD-L1.
6. Stopień sprawności WHO/ECOG PS: 0 lub 1.
7. Adekwatna czynność narządowa i szpiku.
8. Wymagana oczekiwana dalsza długość życia powyżej 3 miesięcy.
E.4Principal exclusion criteria
•Histologically or cytologically confirmed small cell esophageal carcinoma, esophageal adenocarcinoma or other mixed carcinoma.
•Prior anti-cancer treatment for ESCC.
•Patient with a great risk of perforation and massive bleeding.
•History of allogeneic organ transplantation.
•Active or prior documented autoimmune or inflammatory disorders.
•Uncontrolled intercurrent illness.
•History of another primary malignancy.
•Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus.
•Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
1. Histologicznie lub cytologicznie potwierdzony drobnokomórkowy rak przełyku, gruczolakorak przełyku lub inny rak typu mieszanego.
2. Uprzednie leczenie przeciwnowotworowe raka płaskonabłonkowego przełyku (ESCC).
3. Pacjenci z dużym ryzykiem perforacji oraz rozległego krwawienia.
4. Allogeniczny przeszczep narządu w wywiadzie.
5. Aktywne lub wcześniej udokumentowane choroby autoimmunologiczne lub zapalne.
6. Nieleczona choroba współwystępująca.
7. Inny pierwotny nowotwór złośliwy w wywiadzie.
8. Aktywne zakażenie, w tym gruźlica, wirusowe zapalenie wątroby typu B, wirusowe zapalenie wątroby typu C (HCV) lub HIV.
9. Stwierdzona alergia lub nadwrażliwość na jakikolwiek badany lek lub substancje pomocnicze wchodzące w skład badanego leku.
E.5 End points
E.5.1Primary end point(s)
PFS using BICR assessments according to RECIST 1.1 all randomized patients and in patients with PD-L1 High tumors
PFS (wg kryteriów RECIST 1.1, zgodnie z oceną BICR) u wszystkich zrandomizowanych pacjentów i u pacjentów z guzami z wysoką ekspresją PD-L1
E.5.1.1Timepoint(s) of evaluation of this end point
up to 56 months
do 56 miesięcy
E.5.2Secondary end point(s)
- OS, OS36, PFS2
- APF24,ORR, DoR, DCR and TTP per RECIST 1.1 as assessed by BICR
- Time to deterioration and change from baseline in symptoms, functioning, and HRQoL as measured by EORTC QLQ-C30 and QLQ-OES18
- Concentration of durvalumab in blood
- ADA (confirmatory results: positive or negative; titers
- Presence of ADA for durvalumab (confirmatory results: positive or negative; titers)
in all randomized patients and in patients with PD-L1 High tumors
1. OS, OS36, PFS2
2. APF24,ORR, DoR, DCR i TTP wg kryteriów RECIST 1.1, zgodnie z oceną BICR
3. Czas do pogorszenia i zmiana od punktu początkowego w ocenie objawów, funkcjonowania i HRQoL, oceniane za pomocą kwestionariuszy EORTC QLQ-C30 i QLQ-OES18
4. Stężenie durwalumabu we krwi
5. ADA (wyniki potwierdzające: dodatnie lub ujemne; miana) u wszystkich zrandomizowanych pacjentów i u pacjentów z guzami z wysoką ekspresją PD-L1
E.5.2.1Timepoint(s) of evaluation of this end point
Until end of study
do zakończenia badania
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 Yes
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response Yes
E.6.10Pharmacogenetic Yes
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic Yes
E.6.13Others Yes
E.6.13.1Other scope of the trial description
Healthcare resource utilization, Quality of life
Wykorzystanie zasobów służby zdrowia, jakość życia
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 No
E.8.1.3Single blind No
E.8.1.4Double blind Yes
E.8.1.5Parallel group Yes
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) No
E.8.2.2Placebo Yes
E.8.2.3Other No
E.8.2.4Number of treatment arms in the trial2
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 concerned5
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA29
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 No
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
Brazil
Canada
China
Japan
Korea, Republic of
Taiwan
Thailand
United States
Russian Federation
Belgium
France
Netherlands
Poland
Spain
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
Last Subject Last Visit
„LVLS” (Last Visit Last Subject)
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years5
E.8.9.1In the Member State concerned months10
E.8.9.1In the Member State concerned days
E.8.9.2In all countries concerned by the trial years6
E.8.9.2In all countries concerned by the trial months2
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1.1In Utero No
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.3Newborns (0-27 days) No
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.5Children (2-11years) No
F.1.1.6Adolescents (12-17 years) No
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 260
F.1.3Elderly (>=65 years) Yes
F.1.3.1Number of subjects for this age range: 340
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 state26
F.4.2 For a multinational trial
F.4.2.1In the EEA 125
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)
After the final analysis, AstraZeneca will continue to supply durvalumab to patients in durvalumab arn up to objective disease progression if treatment is less than 24 months
Po przeprowadzeniu analizy końcowej, AstraZeneca będzie nadal dostarczać durwalumab pacjentom z grupy przyjmującej durwalumab do chwili obiektywnej progresji choroby, jeżeli okres leczenia wynosił mniej niż 24 miesiące.
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 Decision2021-03-12
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2021-01-21
P. End of Trial
P.End of Trial StatusOngoing

Sponsors and Collaborators

Medical Conditions

Drug Interventions

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