Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ongoing, recruitment ended
Participants planned
523
Countries
4
Sites
21
Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma
To assess the efficacy of durvalumab + dCRT compared with placebo + dCRT in terms of PFS using BICR assessments according to RECIST 1.1 in patients with PD-L1 TAP≥1% tumors
Key facts
- Sponsor
- Astrazeneca AB
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 31 Mar 2021 → ongoing
- Decision date (initial)
- 2024-04-22
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- AstraZeneca AB
External identifiers
- EU CT number
- 2023-506413-22-00
- EudraCT number
- 2020-001001-22
- ClinicalTrials.gov
- NCT04550260
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Pharmacogenetic, Efficacy, Pharmacokinetic, Therapy, Dose response, Pharmacoeconomic
To assess the efficacy of durvalumab + dCRT compared with placebo + dCRT in terms of PFS using BICR assessments according to RECIST 1.1 in patients with PD-L1 TAP≥1% tumors
Secondary objectives 1
- 1) To assess the efficacy of durvalumab + dCRT compared with placebo + dCRT in terms of PFS using BICR assessments according to RECIST 1.1 in all randomized patients 2) To assess the efficacy of durvalumab + dCRT compared to placebo + dCRT in terms of OS, APF24, ORR, DoR, DCR, - --TTP, PFS2, and OS36 in all randomized patients and in patients with PD-L1 TAP≥1% tumors 3)To assess patient-reported symptoms, functioning, and HRQoL in patients treated with durvalumab + dCRT compared to placebo + dCRT using patient reported outcome measures 4)To assess the PK of durvalumab when in combination with dCRT in all randomized patients 5)To investigate the immunogenicity of durvalumab and durvalumab in combination with dCRT in all randomized patients
Conditions and MedDRA coding
Locally Advanced Unresectable Esophageal Squamous Cell Carcinoma
Study design 3 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Screening Period Participants will undergo screening evaluations to determine eligibility prior to first treatment
|
Randomised Controlled | Double | [{"id":174760,"code":3,"name":"Monitor"},{"id":174763,"code":1,"name":"Subject"},{"id":174761,"code":5,"name":"Carer"},{"id":174762,"code":4,"name":"Analyst"},{"id":174764,"code":2,"name":"Investigator"}] | Arm 1: Durvalumab + definitive CRT: Arm 1: Durvalumab + concurrent chemoradiation Arm 2: Placebo + definitive CRT: Arm 2: Placebo + concurrent chemoradiation |
| 2 | Treatment Period All participants will be randomized in a 2:1 ratio to one of the following intervention groups - experimental arm or placebo arms
|
Randomised Controlled | Double | [{"id":174770,"code":2,"name":"Investigator"},{"id":174769,"code":3,"name":"Monitor"},{"id":174766,"code":1,"name":"Subject"},{"id":174767,"code":4,"name":"Analyst"},{"id":174768,"code":5,"name":"Carer"}] | Arm 1: Durvalumab + definitive CRT: Durvalumab + concurrent chemoradiation Arm 2: Placebo + definitive CRT: Placebo + concurrent chemoradiation |
| 3 | Follow-up Period All participants will be followed up for safety assessments at 30 days, month2, and month3 after their last dose of study intervention.
|
Randomised Controlled | Double | [{"id":174772,"code":2,"name":"Investigator"},{"id":174774,"code":4,"name":"Analyst"},{"id":174775,"code":3,"name":"Monitor"},{"id":174773,"code":1,"name":"Subject"},{"id":174776,"code":5,"name":"Carer"}] | Arm 1: Durvalumab + definitive CRT: Arm 1: Durvalumab + concurrent chemoradiation Arm 2: Placebo + definitive CRT: Arm 2: Placebo + concurrent chemoradiation |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- • 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.
Exclusion criteria 1
- • 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 interventions or any of the study interventions excipients.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- PFS using BICR assessments according to RECIST 1.1 in patients with PD-L1 TAP≥1% tumors
Secondary endpoints 1
- PFS using BICR assessments according to RECIST 1.1 in all randomized patients OS, OS36, PFS2 APF24,ORR, DoR, DCR and TTP per RECIST 1.1 as assessed by BICR in all randomized patients and in patients with PD-L1 TAP≥1% tumors 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 in all randomized patients
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
IMFINZI 50 mg/mL concentrate for solution for infusion.
PRD6651398 · Product
- Active substance
- Durvalumab
- Substance synonyms
- MEDI4736
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 1500 mg milligram(s)
- Max total dose
- 1500 mg milligram(s)
- Max treatment duration
- 24 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01XC28 — -
- Marketing authorisation
- EU/1/18/1322/001
- MA holder
- ASTRAZENECA AB
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
N/A · Product
- Other product name
- N/A
- Pharmaceutical form
- N/A
- ATC code
- N/A — N/A
- Marketing authorisation
- N/A
- MA holder
- N/A
- MA country
- Iceland
- Paediatric formulation
- No
Auxiliary 6
Inflectra 100 mg powder for concentrate for solution for infusion
PRD6488927 · Product
- Active substance
- Infliximab
- Substance synonyms
- ABP 710, CT-P13, NI-071, PF-06438179, R-TPR-015
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 9999999 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AB02 — -
- Marketing authorisation
- EU/1/13/854/002
- MA holder
- PFIZER EUROPE MA EEIG
- MA country
- Liechtenstein
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Fluorouracil Injection, 50 mg/ml, solution for injection
PRD536190 · Product
- Active substance
- Fluorouracil
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS INJECTION
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 9999999 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01BC02 — FLUOROURACIL
- Marketing authorisation
- PL 11587/0015
- MA holder
- MEDAC GESELLSCHAFT FÜR KLINISCHE SPEZIALPRÄPARATE MBH (WEDEL)
- MA country
- XI
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Capecitabine Accord 500 mg film-coated tablets
PRD1614134 · Product
- Active substance
- Capecitabine
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 9999999 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01BC06 — CAPECITABINE
- Marketing authorisation
- EU/1/12/762/025
- MA holder
- ACCORD HEALTHCARE S.L.U.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Capecitabine Accord 150 mg film-coated tablets
PRD1614128 · Product
- Active substance
- Capecitabine
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 9999999 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01BC06 — CAPECITABINE
- Marketing authorisation
- EU/1/12/762/019
- MA holder
- ACCORD HEALTHCARE S.L.U.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Mycophenolate Mofetil Accord 250 mg capsules
PRD391904 · Product
- Active substance
- Mycophenolate Mofetil
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 9999999 Month(s)
- Authorisation status
- Authorised
- ATC code
- L04AA06 — MYCOPHENOLIC ACID
- Marketing authorisation
- PA 2315/064/001
- MA holder
- ACCORD HEALTHCARE IRELAND LIMITED
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Cisplatin 1 mg/ml Concentrate for Solution for Infusion
PRD1168083 · Product
- Active substance
- Cisplatin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 00 mg milligram(s)
- Max total dose
- 00 mg milligram(s)
- Max treatment duration
- 9999999 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01XA01 — CISPLATIN
- Marketing authorisation
- PA 0822/199/001
- MA holder
- PFIZER HEALTHCARE IRELAND
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Astrazeneca AB
- Sponsor organisation
- Astrazeneca AB
- Address
- Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674
- City
- Sodertalje
- Postcode
- 151 85
- Country
- Sweden
Scientific contact point
- Organisation
- Astrazeneca AB
- Contact name
- AstraZeneca Clinical Study Information Centre
Public contact point
- Organisation
- Astrazeneca AB
- Contact name
- AstraZeneca Clinical Study Information Center
Locations
4 EU/EEA countries · 21 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Belgium | Ongoing, recruitment ended | 11 | 4 |
| France | Ongoing, recruitment ended | 15 | 7 |
| Poland | Ongoing, recruitment ended | 5 | 3 |
| Spain | Ongoing, recruitment ended | 17 | 7 |
| Rest of world
United States, Korea, Republic of, Taiwan, Thailand, Turkey, Mexico, Vietnam, China, Brazil, Japan, Russian Federation, Canada
|
— | 475 | — |
Investigational sites
UZ Brussel
Medische Oncologie, Laarbeeklaan 101, 1090, Jette
Grand Hopital De Charleroi
Service d'oncologie et hématologie, Rue Du Campus Des Viviers 1, 6060, Charleroi
Centre Hospitalier Universitaire Dinant Godinne Sainte-Elisabeth-UCL-Namur
Medical Oncology, Place Louise Godin 15, 5000, Namur
CHC MontLegia
Département d'Oncologie/Hématologie, Boulev. De Patience Et Beajonc 2, 4000, Liege
HPM Nord
Oncology, 44 Avenue Marx Dormoy, 59000, Lille
Courlancy Sante
Oncology, 109 Rue Louis Victor De Broglie, 51430, Bezannes
Institut De Cancerologie Strasbourg Europe
Medical Oncology, 17 Rue Albert Calmette, 67200, Strasbourg
Besancon University Hospital Center
Oncology, 3 Boulevard Alexander Fleming, Cs 81816, Besancon Cedex
CHU De Rouen
Gastro enterology, 1 Rue De Germont, Bp 96031, Rouen Cedex
Hopital Prive Jean Mermoz
Oncology, 55 Avenue Jean Mermoz, 69008, Lyon
Institut Gustave Roussy
Digestive Oncology, 114 Rue Edouard Vaillant, 94800, Villejuif
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Klinika Onkologii i Radioterapii, Ul. Wawelska 15, 02-034, Warsaw
Katowickie Centrum Onkologii
Zaklad Radioterapii, ul. Raciborska 27, 40-074, Katowice
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
n/a, Ul. Garncarska 11, 31-115, Cracow
Hospital Unviersitario Miguel Servet
Oncologia, Paseo De Isabel La Catolica 1-3, 50009, Zaragoza
Hospital General Universitario Gregorio Maranon
Oncologia, Calle Del Doctor Esquerdo 46, 28007, Madrid
Hospital Universitario De Navarra
Oncologia, Irunlarrea Kalea 3, 31008, Pamplona
Hospital General Universitario Reina Sofia
Oncologia, Avenida Menendez Pidal S/n, 14004, Cordoba
Hospital Universitario Marques De Valdecilla
Oncologia, Avenida Valdecilla Sn, 39008, Santander
Hospital Universitari Vall D Hebron
Oncologia, Edificio Materno-Infantil, Passeig De La Vall D'hebron 119-129, Barcelona
Hospital Universitario La Paz
Oncologia, Paseo De La Castellana 261, 28046, Madrid
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Belgium | 2021-05-10 | 2021-07-02 | 2023-09-18 | ||
| France | 2021-07-13 | 2021-07-20 | 2023-09-18 | ||
| Poland | 2021-07-07 | 2021-07-19 | 2023-09-18 | ||
| Spain | 2021-03-31 | 2021-05-31 | 2023-09-18 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 24 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol redacted 2023-506413-22-00 | 3 |
| Recruitment arrangements (for publication) | CTIS Blank Document for Transition Trials | n/a |
| Recruitment arrangements (for publication) | CTIS Blank Document for Transition Trials | n/a |
| Recruitment arrangements (for publication) | CTIS Blank Document for Transition Trials | n/a |
| Recruitment arrangements (for publication) | CTIS Blank Document for Transition Trials | n/a |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF Adult BE Dutch_Redacted | 6 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF Adult BE English_redacted | 6 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF Adult BE French_redacted | 6 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF Adult PL_Redacted | 7 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF Adult_redacted | 6 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF Genetic | 1 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF genetic subject PL | 1.1 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF Pregnant | 1 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF pregnant partner PL | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults_main_Fr_redacted | 4 |
| Subject information and informed consent form (for publication) | L2_ Other subject information material ICF optional genetic_Fr | 2 |
| Subject information and informed consent form (for publication) | L2_ Other subject information material ICF pregnant partners of study subjects_Fr | 1.2 |
| Synopsis of the protocol (for publication) | D1_ Protocol synopsis CTD_FR_EU CTR 2023-506413-22-00_redacted | 3 |
| Synopsis of the protocol (for publication) | D1_Protocol lay synopsis_FR_2023-506413-22-00 | 1.0 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_Lay language_BE_Dutch 2023-506413-22 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_Lay language_BE_French 2023-506413-22 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_Lay language_BE_German 2023-506413-22 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_Lay language_ES_2023-506413-22-00 | 1.0 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis_lay language_PL_2023-506413-22 | 1 |
Application history
8 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-03-14 | Belgium | Acceptable 2024-04-05
|
2024-04-08 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-07-15 | Acceptable | 2024-07-24 | |
| 3 | SUBSTANTIAL MODIFICATION | SM-3 | 2024-10-07 | Belgium | Acceptable 2024-11-19
|
2024-11-20 |
| 4 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-04-07 | Belgium | Acceptable | 2025-05-07 |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-08-22 | Belgium | Acceptable | 2025-08-22 |
| 6 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2026-01-09 | Belgium | Acceptable | 2026-01-09 |
| 7 | SUBSTANTIAL MODIFICATION | SM-5 | 2026-02-24 | Acceptable | 2026-03-23 | |
| 8 | SUBSTANTIAL MODIFICATION | SM-6 | 2026-03-05 | Belgium | Acceptable | 2026-05-12 |