Informations générales (source: ClinicalTrials.gov)
A Randomized, Double-blind, Placebo-controlled Phase 3 Trial of Pembrolizumab (MK-3475) Versus Placebo in Participants With Esophageal Carcinoma Receiving Concurrent Definitive Chemoradiotherapy (KEYNOTE 975)
Interventional
Phase 3
Merck Sharp & Dohme LLC (Voir sur ClinicalTrials)
février 2020
février 2027
16 novembre 2024
The purpose of this study is to assess the efficacy and safety of treatment with
definitive chemoradiotherapy (dCRT) + pembrolizumab (MK-3475) compared to treatment with
dCRT + placebo with respect to Event-free Survival (EFS) and Overall Survival (OS) in:
- participants whose tumors express Programmed Death-Ligand 1 (PD-L1) Combined
Positive Score (CPS) ≥10
- participants whose tumors express PD-L1 CPS ≥1
- all participants
The primary study hypotheses are that dCRT+ pembrolizumab is better than dCRT + placebo
with respect to:
- EFS in participants whose tumors express PD-L1 CPS ≥10
- EFS in participants whose tumors express PD-L1 CPS ≥1
- EFS in all participants
- OS in participants whose tumors express PD-L1 CPS ≥10
- OS in participants whose tumors express PD-L1 CPS ≥1
- OS in all participants
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 04/06/2024 14:01:25 | Contact (sur clinicalTrials) | |||
| CLCC RENE HUGUENIN INSTITUT CURIE | 04/12/2024 12:44:05 | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Francois Baclesse ( Site 0236) - 14075 - Caen - Calvados - France | Contact (sur clinicalTrials) | ||||
| Centre Georges Francois Leclerc ( Site 0223) - 21079 - Dijon - Cote-d Or - France | Contact (sur clinicalTrials) | ||||
| CHD Vendee ( Site 0227) - 85925 - La Roche sur Yon - Vendee - France | Contact (sur clinicalTrials) | ||||
| CHU Amiens Picardie Site Sud Amiens ( Site 0235) - 80054 - Amiens - Somme - France | Contact (sur clinicalTrials) | ||||
| CHU Hotel Dieu Nantes ( Site 0230) - 44093 - Nantes - Pays-de-la-Loire - France | Contact (sur clinicalTrials) | ||||
| CHU Limoges Hopital Dupuytren ( Site 0225) - 87042 - Limoges - Haute-Vienne - France | Contact (sur clinicalTrials) | ||||
| Institut De Cancerologie De Lorraine ( Site 0222) - 54519 - Vandoeuvre les Nancy - Ain - France | Contact (sur clinicalTrials) | ||||
| Institut Jean Godinot ( Site 0238) - 51726 CEDEX - Reims - Marne - France | Contact (sur clinicalTrials) | ||||
| Institut Sainte Catherine ( Site 0228) - 84918 - Avignon - Provence-Alpes-Cote-d Azur - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion Criteria:
- Has histologically or cytologically confirmed diagnosis of CTX N+ M0 or cT2-T4a NX
M0 ESCC, GEJC, EAC, or histologically or cytologically confirmed diagnosis of cTX N+
M1 cervical or upper thoracic esophageal carcinoma with supraclavicular lymph node
metastases only
- Is deemed suitable for dCRT
- Is ineligible for curative surgery based on the documented opinion of a qualified
medical/surgical/radiation oncologist.
- Is not expected to require tumor resection during the course of the study
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within
3 days of the first dose of study treatment
- Has adequate organ function
- Male participants must use adequate contraception (a male condom plus partner use of
an additional contraceptive method) unless confirmed to be azoospermic (vasectomized
or secondary to medical cause) and refrain from donating sperm during the study
treatment period and through 90 days after the last dose of chemotherapy
- Female participants who are a Woman of Childbearing Potential (WOCBP) must use
contraception that is highly effective (with a failure rate of <1% per year), with
low user dependency, or be abstinent from heterosexual intercourse as their
preferred and usual lifestyle, during the study treatment period through 180 days
after the last dose of chemotherapy or 120 days after the last dose of
pembrolizumab, whichever is greater, and agree not to donate eggs to others or
freeze/store for her own use for the purpose of reproduction during this period
- Female participants must not be pregnant or breastfeeding
- Has histologically or cytologically confirmed diagnosis of CTX N+ M0 or cT2-T4a NX
M0 ESCC, GEJC, EAC, or histologically or cytologically confirmed diagnosis of cTX N+
M1 cervical or upper thoracic esophageal carcinoma with supraclavicular lymph node
metastases only
- Is deemed suitable for dCRT
- Is ineligible for curative surgery based on the documented opinion of a qualified
medical/surgical/radiation oncologist.
- Is not expected to require tumor resection during the course of the study
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within
3 days of the first dose of study treatment
- Has adequate organ function
- Male participants must use adequate contraception (a male condom plus partner use of
an additional contraceptive method) unless confirmed to be azoospermic (vasectomized
or secondary to medical cause) and refrain from donating sperm during the study
treatment period and through 90 days after the last dose of chemotherapy
- Female participants who are a Woman of Childbearing Potential (WOCBP) must use
contraception that is highly effective (with a failure rate of <1% per year), with
low user dependency, or be abstinent from heterosexual intercourse as their
preferred and usual lifestyle, during the study treatment period through 180 days
after the last dose of chemotherapy or 120 days after the last dose of
pembrolizumab, whichever is greater, and agree not to donate eggs to others or
freeze/store for her own use for the purpose of reproduction during this period
- Female participants must not be pregnant or breastfeeding
- Has direct invasion of tumor into adjacent organs such as the aorta or trachea or
has radiographic evidence of >90 degree encasement or invasion of a major blood
vessel, or of intratumoral cavitation
- Has had major surgery other than for insertion of a feeding tube, open biopsy, or
significant traumatic injury within 28 days prior to randomization, or anticipates
the need for major surgery during study treatment; participants with gastric or
esophageal fistulae are excluded
- Has had weight loss of >20% in the previous 3 months
- Has had prior chemotherapy or radiotherapy for esophageal cancer
- Has had a myocardial infarction within the past 6 months
- Has symptomatic congestive heart failure
- Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1),
anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell
death-ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory
or coinhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4
[CTLA-4], OX-40, CD137)
- Has received a live or live-attenuated vaccine within 30 days prior to the first
dose of study intervention; administration of killed vaccines is allowed
- Has received any prior systemic anticancer therapy for esophageal cancer including
investigational agents
- Has not recovered from all adverse events (AEs) due to previous non-anticancer
therapies to ≤Grade 1 or Baseline
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
or any other form of immunosuppressive therapy within 7 days prior the first dose of
study treatment
- Has a known additional malignancy that is progressing or has required active
treatment within the past 3 years. Note: Participants with basal cell carcinoma of
the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast
carcinoma, cervical cancer in situ) that have undergone potentially curative therapy
are not excluded from the study. Participants with localized prostate cancer that
has undergone potentially curative treatment can be enrolled in the study.
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab, any of the study
chemotherapy agents, or their excipients
- Has an active autoimmune disease that has required systemic treatment in past 2
years
- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis
- Has an active infection requiring systemic therapy
- Has a known history of human immunodeficiency virus (HIV) infection
- Has a known history of Hepatitis B or known active Hepatitis C virus infection
- Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
- Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of study treatment (180 days for participants receiving
cisplatin who are breastfeeding)
- Has had an allogeneic tissue/solid organ transplant