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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04704934
Other study ID # DS8201-A-U306
Secondary ID 2020-004559-34
Status Recruiting
Phase Phase 3
First received
Last updated
Start date May 21, 2021
Est. completion date February 1, 2026

Study information

Verified date May 2024
Source Daiichi Sankyo
Contact (EU & UK sites) Daiichi Sankyo Contact for Clinical Trial Inform
Phone 908-992-6400
Email CTRinfo@dsi.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study will evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) compared with ramucirumab and paclitaxel (Ram + PTX) in participants with HER2-positive gastric or gastro-esophageal junction (GEJ) adenocarcinoma who have progressed on or after a trastuzumab-containing regimen and have not received any additional systemic therapy.


Description:

This study will assess the efficacy and safety of T-DXd compared with Ram + PTX in participants with HER2-positive (defined as immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization [ISH]+) gastric or GEJ adenocarcinoma (based on [American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines who have progressed on or after a trastuzumab-containing regimen and have not received any additional systemic therapy. Participants will be randomized 1:1 to either T-DXd or Ram + PTX treatment. The primary objective will assess overall survival. Secondary objectives will further assess progression-free survival, objective response rate, duration of response, disease control rate, safety, pharmacokinetics, and immunogenicity of T-DXd.


Recruitment information / eligibility

Status Recruiting
Enrollment 490
Est. completion date February 1, 2026
Est. primary completion date October 1, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Adults (according to local regulation) and able to provide informed consent for study participation. - Pathologically documented gastric and GEJ adenocarcinoma that has been previously treated in the metastatic setting (unresectable, locally advanced, or metastatic disease). - Progression on or after first-line therapy with a trastuzumab or approved trastuzumab biosimilar-containing regimen. Note: Prior neoadjuvant or adjuvant therapy with a trastuzumab-containing regimen can be counted as a line of therapy if the subject progressed on or within 6 months of completing neoadjuvant or adjuvant therapy. Prior neoadjuvant or adjuvant therapy that does not include trastuzumab will not be counted as a line of therapy regardless of the progression status of the subject. - Locally or centrally confirmed HER2-positive (IHC 3+ or IHC 2+ and evidence of HER2 amplification by ISH) as classified by ASCO-CAP on a tumor biopsy obtained after progression on or after a first-line trastuzumab or approved trastuzumab biosimilar-containing regimen. - Eastern Cooperative Oncology Group performance status of 0 or 1 at Screening. - Adequate bone marrow, renal, hepatic function, and blood clotting function within 14 days of randomization. Exclusion Criteria: - Use of anticancer therapy after trastuzumab-containing treatment - Medical history of myocardial infarction (MI) within 6 months before randomization/enrollment, symptomatic congestive heart failure (New York Heart Association Class II to IV). - Has a QT interval corrected by Fridericia's formula (QTcF) prolongation to >470 msec (female subjects) or >450 msec (male subjects) based on average of the Screening triplicate12-lead ECG. - Has a history of (non-infectious) interstitial lung disease (ILD/pneumonitis) that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening. - Any autoimmune, connective tissue or inflammatory disorders (eg, rheumatoid arthritis, Sjögren syndrome, sarcoidosis, etc.) where there is documented (or a suspicion of) pulmonary involvement at the time of Screening. - Prior complete pneumonectomy. - Spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. - Has multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, other solid tumors curatively treated. - History of severe hypersensitivity reactions to either the T-DXd or inactive ingredients in T-DXd. - History of severe hypersensitivity reactions to other monoclonal antibodies, including ramucirumab or to any of its excipients. - Known allergy or hypersensitivity to paclitaxel or any components used in the paclitaxel preparation or other contraindication for taxane therapy. - Current uncontrolled infection requiring antibiotics, antivirals, or antifungals or an unexplained fever >38.0°C during Screening visits or on the first scheduled day of dosing (at the discretion of the Investigator, participants with tumor fever may be enrolled), which in the Investigator's opinion might compromise the participant's participation in the study or affect the study outcome - Clinically significant gastrointestinal disorder (eg, including hepatic disorders, bleeding, inflammation, occlusion, ileus, diarrhea Grade >1, jaundice, intestinal paralysis, malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, or partial bowel obstruction) in the opinion of Investigator - Has history of receiving live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first exposure to study intervention

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Trastuzumab deruxtecan
6.4 mg/kg IV infusion every 3 weeks on Day 1 of each 21-day cycle
Ramucirumab
8 mg/kg IV infusion on Days 1 and 15 of a 28-day cycle
Paclitaxel
80 mg/m^2 IV infusion on Days 1, 8, and 15 of a 28-day cycle

Locations

Country Name City State
Argentina Fundacion Cenit Buenos Aires
Argentina Instituto Medico Especializado Alexander Fleming Colegiales Caba
Argentina IONC Instituto Oncologico de Cordoba - Fundacion Richardet Longo Nueva Cordoba Cordoba
Argentina Exelsus San Miguel De Tucumán Tucumán
Belgium UCL St. Luc Brussels
Belgium Antwerp University Hospital Edegem
Belgium Pôle Hospitalier Jolimont Haine-Saint-Paul
Belgium UZ Leuven Leuven
Brazil PERSONAL - Oncologia de Precisao e Personalizada Belo Horizonte
Brazil Hospital Sirio Libanes Brasilia
Brazil ONCOSITE - Centro de Pesquisa Clinica em Oncologia LTDA Ijui
Brazil Hospital Ernesto Dornelles Porto Alegre
Chile Clinica San Carlos de Apoquindo Santiago Region Metropolitana
Chile Fundacion Arturo Lopez Perez Santiago Region Metropolitana
Chile SIM Centro de Investigacion Clinica Temuco Cautin
China Beijing Cancer Hospital Beijing
China Peking Univ 3rd Hosp Beijing
China The 1st Hospital of Jilin Univ Changchun
China Zhongnan univ Xiangya hosp Changshan Hunan
China Fujian Medical University - Fujian Provincial Cancer Hospital Fuzhou Fuijan
China 1Affiliated H of Sun Yat Sen U Guangzhou Guangdong
China The Sixth Affiliated Hospital of Sun Yat-Sen University Guangzhou Guangdong
China Sir Run Run Shaw Hospital Hangzhou
China Zhejiang Medical University - Zhejiang Cancer Hospital Hangzhou Zhejiang
China Harbin Medical University Cancer Hospital Harbin Heilongjiang
China Anhui Provincial Hospital Heifi Anhui
China Shandong Cancer Hospital & Institute Jinan Shandong
China Linyi Cancer Hospital Linyi
China 1 Affiliated H of Nanchang U Nanchang
China Jiangsu Province Hosp Nanjing Jiangsu
China Fudan University - Shanghai Cancer Center Shanghai
China Shanghai First People's Hosp Shanghai Shanghai
China Zhongshan Hosp Fudan Univ Shanghai Shanghai
China 1st Hosp of China Medical Univ Shenyang Liaoning
China Liaoning Cancer Hospital Shenyang Liaoning
China Hebei Medical Univ 4th Hosp Shijiazhuang Hebei
China Xinjiang Medical University - Cancer Hospital Urumqi Xinjiang
China Xiamen University - The First Affiliated Hospital Xiamen Fujian
China The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan
France CHU Besançon Besancon
France CHRU Brest
France Centre Oscar Lambret Lille
France Centre Leon Berard Lyon Cedex 08
France Hopital de la Timone Marseille
France Institut de Recherche en Cancerologie de Montpellier IRCM Montpellier
France Hopital Europeen G. Pompidou Paris
France Hopital Saint Antoine Paris
France L Institut Mutualiste Montsouris Paris
France Centre Hospitalier Universitaire CHU de Rennes - Hopital de Pontchaillou Rennes
France Pharmacie ICLN Saint-Priest-en-Jarez
France Gustave Roussy, étage -1. Villejuif
Germany Charité-Unimedizin Berlin Berlin
Germany Uniklinikum Carl-Gustav-Carus Dresden Sachsen
Germany Evang. Klin. Essen-Mitte gGmbH Essen
Germany Ins. für klinische onk. Forschung Frankfurt Am Main Hessen
Germany Asklepios Tumorzentrum Altona Hamburg
Germany Häm-Onk. Praxis Eppendorf Hamburg
Germany Uni zu Koln-Unikl. Koln Kln Nordrhein-westfalen
Germany Universitares Krebszentrum Leipzig
Hong Kong Pamela Youde Nethersole Eastern Hospital Chai Wan
Hong Kong Princess Margaret Hospital Hong Kong
Hong Kong Queen Mary Hospital Hong Kong
Hong Kong The Chinese University of Hong Kong (CUHK) - Prince of Wales Hospital (PWH) - Vascular and Interventional Radiology Foundation (VIRF) Clinical Science Centre Hong Kong
Hungary Magyar Honvedseg Egeszs. K Budapest
Hungary Debreceni Egyetem Klinikai Debrecen
Hungary Tolna M. Balassa Janos Korhaz Szekszard
Ireland Cork University Hospital Cork
Ireland Beaumont Hospital Dublin
Ireland St James's Hospital Dublin
Ireland Tallaght University Hospital Dublin
Israel Soroka Univ Medical CTR Be'er-Sheva Southern
Israel Davidoff Center Petach Tikva
Israel The Chaim Sheba Medical Center Ramat Gan
Italy AOU Pisana Barone
Italy IRCC-FPO Candiolo Candiolo
Italy AOU Mater Domini Catanzaro
Italy Istituto Europeo di Oncologia S.r.L Divisione di Oncologia Medica Gastrointestinale e Tumori Neuroendocrini Milan
Italy Ospedale Niguarda Milan
Italy Istituto Nazionale dei Tumori Milano
Italy San Raffaele Hospital Milano
Italy Azienda Ospedaliero-Universitaria di Modena Modena
Italy Aou Vanvitelli Napoli
Italy Istituto Oncologico Veneto Padua
Italy Azienda Ospedaliero-Universitaria Pisana Pisa
Japan National Cancer Center Hospital Chuo Ku
Japan Osaka International Cancer Institute Chuo Ku
Japan Gifu University Hospital Gifu
Japan National Cancer Center Hospital East Kashiwa
Japan Kobe City Medical Center General Hospital Kobe
Japan Kochi Health Sciences Center Kochi
Japan The Cancer Institute Hospital of JFCR Koto-Ku
Japan National Hospital Organization Shikoku Cancer Center Matsuyama
Japan Aichi Cancer Center Hospital Nagoya-shi Aichia
Japan Niigata Cancer Center Hospital Niigata
Japan Kindai University Hospital Osaka-sayama
Japan Osaka University Hospital Suita
Korea, Republic of Kyungpook Nat Uni Chilgok Hos Daegu
Korea, Republic of Chonnam National University Hwasun Hospital Hwasun
Korea, Republic of Seoul Nati Univ Bundang Hosp Seongnam
Korea, Republic of Asan Medical Center Seoul
Korea, Republic of Chonbuk National University Hospital - Jeonbuk Regional Cancer Center Seoul
Korea, Republic of Korea Univ Anam Hosp Seoul
Korea, Republic of Samsung Medical Center Seoul
Korea, Republic of Seoul National University Hospital Seoul
Korea, Republic of Seoul St. Marys Hospital Seoul
Korea, Republic of Severance Hospital Seoul
Poland Sklodowska-Curie Inst Oncology Warszawa
Poland Uniwersytecki Szpital Kliniczny im.Mikulicza-Radeckiego Wroclaw
Portugal Hospital Sra da Oliveira Creixomil E Mariz
Portugal Instituto Portugues De Oncologia Do Porto Francisco Gentil, E.P.E. Porto
Portugal C Hosp Tras Montes Alto Douro Vila Real
Romania S.C. Oncopremium-Team SRL Baia Mare
Romania Institutul Oncologic Prof. Dr. Alexandru Trestiorean Bucuresti IOB Bucharest
Romania S.C. Medisprof SRL Cluj-Napoca
Romania Centrul de Oncologie Sf. Nectarie Craiova
Russian Federation SBIH Chelyabinsk Regional Clinical Centre of Oncology and Nuclear Medicine Chelyabinsk
Russian Federation City Clinical Oncology Dispensary Saint-Petersburg
Russian Federation Private Medical Institution "Euromedservice" St.Petersburg
Russian Federation Republican Clinical Oncology Dispensary Ufa
Singapore National Cancer Centre Singapore Singapore
Singapore National Univ Cancer Inst SGP Singapore
Spain Hospital Clinic de Barcelona Barcelona
Spain Hospital Germans Trias i Pujol Barcelona
Spain Hospital Vall d'Hebron Barcelona
Spain H. Gregorio Maranon Madrid
Spain Hosp Univ Ramón y Cajal Madrid
Spain Hospital Universitario La Paz Madrid
Spain Hospital de Navarra Pamplona
Spain Hospital Clinico Universitario de Santiago de Compostela Santiago de Compostela
Spain H. Clinico U. de Valencia Valencia
Taiwan CGMF-Kaohsiung Branch Kaohsiung
Taiwan KMUH Kaohsiung
Taiwan China Medical Univ Hosp Taichung
Taiwan National Cheng Kung Univ Hosp Tainan
Taiwan MacKay Memorial Hospital Taipei
Taiwan National Taiwan University Hospital NTUH Taipei
Taiwan Taipei Veterans General Hosp Taipei
Taiwan CGMF-Linkou Branch Taoyuan
Turkey SBU Adana Sehir Hastanesi Adana
Turkey Trakya Universitesi Balkan Edirne
Turkey Suleyman Yalcin Seh. Hast. Istanbul
Turkey Inonu Uni. Turgut Ozal Tip Malatya
Ukraine MedicalCenter ASKLEPION LLC Kyiv
Ukraine National Cancer Institute Kyiv
Ukraine LLC "Oncolife" Zaporizhzhia
United Kingdom Queens University Belfast - Centre for Cancer Research and Cell Biology CCRCB Belfast
United Kingdom University Hospitals Birmingham UHB NHS Foundation Trust - Queen Elizabeth Hospital Birmingham QEHB Birmingham
United Kingdom Addenbrooke's Hospital Cambridge
United Kingdom Velindre NHS Trust - Velindre Cancer Centre VCC Cardiff
United Kingdom Ninewells Hospital Dundee
United Kingdom Beatson West of Scotland Cancer Centre Glasgow
United Kingdom The Clatterbridge Cancer Centre NHS Foundation Trust Liverpool
United Kingdom Royal Marsden NHS London
United Kingdom UCLH Trust London
United Kingdom Christie Hospital Manchester
United Kingdom University of Oxford, The Churchill Hospital Oxford
United Kingdom Royal Marsden Sutton Sutton
United Kingdom Leeds Teaching Hospitals NHS Trust West Yorkshire

Sponsors (2)

Lead Sponsor Collaborator
Daiichi Sankyo AstraZeneca

Countries where clinical trial is conducted

Argentina,  Belgium,  Brazil,  Chile,  China,  France,  Germany,  Hong Kong,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Poland,  Portugal,  Romania,  Russian Federation,  Singapore,  Spain,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Overall Survival in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel Overall survival (OS) is defined as the time from date of randomization until death from any cause. Time from date of randomization until death (due to any cause), up to approximately 36 months
Secondary Progression-free Survival in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel Progression-free survival (PFS) is defined as the time from date of randomization until first objective radiographic tumor progression or death from any cause, based on Investigator assessment. Time from date of randomization until first objective radiographic disease progression or death (due to any cause) whichever occurs first, up to approximately 36 months
Secondary Objective Response Rate in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel Objective response rate (ORR) is defined as the proportion of participants who achieve a best response of complete response (CR) or partial response (PR) using the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria as assessed by Investigator. From start of treatment to date of documented disease progression, up to approximately 36 months
Secondary Duration of Response in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel Duration of response (DoR) is defined time from the initial response (CR or PR) until documented tumor progression or death from any cause and based on Investigator assessment. Time from initial response (CR or PR) to date of documented disease progression or death (due to any cause) whichever occurs first, up to approximately 36 months
Secondary Disease Control Rate in Participants Who Were Administered Trastuzumab Deruxtecan Compared With Ramucirumab in Combination With Paclitaxel Disease control rate (DCR) is defined as the proportion of participants who achieved CR, PR, or stable disease (SD) for a minimum of 6 weeks during study treatment, based on Investigator assessment. From start of treatment to date of documented disease progression, up to approximately 36 months
Secondary Incidence of Treatment-emergent Adverse Events (TEAE), Serious Adverse Events (SAE), Adverse Events of Special Interest (AESI), and Physical Examination Findings Adverse events will be graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0. From time subjects signs informed consent form up to 40 days after last study dose
Secondary Serum Concentrations for Trastuzumab Deruxtecan, total anti-HER2 antibody, and Active Metabolite MAAA-1181a Cycles 1-4 and subsequent cycles on Day 1 pre- and post-infusion (each cycle is 28 days)
Secondary Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) The immunogenicity of trastuzumab deruxtecan will be assessed. Cycles 1, 2, and 4 on Day 1 pre-infusion, then every 4 cycles on Day 1 pre-infusion, 40 day follow up until death, withdrawal of consent, or lost to follow up whichever occurs first (each cycle is 28 days)
Secondary Percentage of Participants Who Have Treatment-emergent ADAs The immunogenicity of trastuzumab deruxtecan will be assessed. Cycles 1, 2, and 4 on Day 1 pre-infusion, then every 4 cycles on Day 1 pre-infusion, 40 day follow up until death, withdrawal of consent, or lost to follow up whichever occurs first (each cycle is 28 days)
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