D00 Carcinoma in situ of oral cavity, oesophagus and stomach Carcinoma in situ of oral cavity, oesophagus and stomach
Conditions
Interventions
None listed
Sponsors
Merck Sharp & Dohme LLC., (una subsidiaria de Merck & Co. Inc.)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Is male or female and is at least 18 years of age on the day of signing informed consent with cTX N+ M0 or cT2-T4 NXM0 ESCC (as defined by AJCC 8th edition), Siewert Type I adenocarcinoma of the EGJ, or EAC, is deemed suitable for dCRT, has disease that is qualitatively evaluable upon radiographic assessment by local site Investigator, and is ineligible for curative surgery based on the documented opinion of a qualified medical/surgical/radiation oncologist 2. Is not be expected to require tumor resection during the course of the study 3. Has an ECOG performance status of 0 to 1 within 3 days of the first dose of study intervention 4. Is adequately nourished per the Investigator’s judgment. A feeding tube is acceptable to maintain adequate nourishment 5. Has provided tumor tissue sample deemed adequate for PD-L1 and MSI biomarker analysis. The PD-L1 result must be determined as positive or negative by the central laboratory and the site notified of its adequacy. Study sites will be masked as to the PDL1 result. A repeat sample will be required if submitted sample is inadequate. 6. Has adequate organ function as defined in Table 1 (see Protocol). Specimens must be collected within 14 days prior to the start of study treatment 7. Male participants are eligible to participate if they agree to the following during the intervention period and through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater: -Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR - Must agree to use contraception as detailed below unless confirmed to be Azoospermic - Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. 8. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: -Is not a Woman of Childbearing Potential (WOCBP) OR -Is a WOCBP and using a contraceptive method 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 -A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] asrequired by local regulations) within 24 hours before the first dose of study intervention. 9. Has (or legally acceptable representative if applicable) provided written informed consent/assent for the study. The participant may also provide consent/assent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research
Exclusion criteria
Exclusion criteria: 1.Has direct invasion of tumor into adjacent organs such as the aorta or trachea (participants with T4b disease are not eligible for study participation). 2.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 anticipation of the need for major surgery during study treatment 3. Has had weight loss of >20% in the previous 3 months 4. Has had prior chemotherapy or RT for esophageal cancer 5. Has had a myocardial infarction within the past 6 months. If the myocardial infarction occurred >6 months ago, participant may be included if no transient ischemia is evidente and at the discretion of the Principal Investigator with input from a cardiologist 6. Has severe congestive heart failure (ie, NYHA Class 2 or higher). 7. Has a history or current evidence of any condition (eg, known deficiency of the enzyme dihydropyrimidine dehydrogenase, hearing impairment, etc), therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant’s participation for the full duration of the trial, or is not in the best interest of the participant to participate (eg, any contraindication to the use of cisplatin or 5-FU), in the opinion of the treating Investigator 8. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137). 9. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. 10. Has received any prior systemic anticancer therapy for esophageal cancer including investigational agents 11. Has not recovered from all AEs due to previous non-anticancer therapies to =Grade 1 or baseline. Participants with =Grade 2 neuropathy may be eligible 12. Is currently participating in or has participated in a study of an investigational agent for a condition or has used an investigational device within 4 weeks prior to the first dose of study intervention 13. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug 14. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years 15. Has severe hypersensitivity (=Grade 3) to pembrolizumab, any of the study chemotherapy agents, or their excipients 16. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed 17. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. Participant should be excluded only if systemic steroids were required 18. Has an active
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Kaplan-Meier Method NAME OF THE RESULT: Overall survival (OS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: The primary analysis will be conducted when all enrolled participants have at least 12 months follow-up. The final analysis will be conducted when all enrolled participants have at least 24 months of follow-up;Kaplan-Meier Method NAME OF THE RESULT: Progression-free Survival (PFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: The primary analysis will be conducted when all enrolled participants have at least 12 months follow-up. The final analysis will be conducted when all enrolled participants have at least 24 months follow-up. | — |
Secondary
| Measure | Time frame |
|---|---|
| Kaplan-Meier Method NAME OF THE RESULT: Overall survival (OS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: The primary analysis will be conducted when all enrolled participants have at least 12 months follow-up. The final analysis will be conducted when all enrolled participants have at least 24 months of follow-up;Kaplan-Meier Method NAME OF THE RESULT: Progression-free Survival (PFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: The primary analysis will be conducted when all enrolled participants have at least 12 months follow-up. The final analysis will be conducted when all enrolled participants have at least 24 months follow-up.;Miettinen and Nurminen Method NAME OF THE RESULT: Proportion of adverse events (AE) and Discontinuation of study intervention due to AEs PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From the treatment period plus 30 days of follow-up | — |
Countries
Argentina, Brazil, Canada, Chile, China, Denmark, Estonia, France, Germany, Guatemala, Hong Kong, Hungary, Italy, Japan, Korea South, Peru, Philippines, Portugal, Romania, Russian Federation, Taiwan, Turkey, United Kindgdom, United States
Outcome results
None listed