Placebo-controlled Trial of Pembrolizumab in Esophageal Carcinoma Participants Receiving Concurrent dCRT
- Conditions
- Esophageal CarcinomaMedDRA version: 21.0 Level: LLT Classification code 10015366 Term: Esophageal carcinoma System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-002006-51-FR
- Lead Sponsor
- Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.,Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 600
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. 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 (vasectomized or secondary to medical cause):
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 (abstinent on a long-term and persistent basis), during the intervention period through 180 days after the last dose of chemotherapy or 120 days after the last dose of pembrolizumab, whichever is greater, and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The Investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention
- A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 24 hours before the first dose of study intervention
The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy
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 evident 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–Guérin (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 insufficienc
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br> Main Objective: 1. To compare definitive chemoradiotherapy (dCRT) + pembrolizumab to dCRT + placebo with respect to overall survival (OS) in participants with esophageal squamous cell carcinoma (ESCC), in participants whose tumors express programmed cell death-ligand 1 (PD-L1) Combined Positive Score (CPS) =10, and in all participants<br> 2. To compare dCRT + pembrolizumab to dCRT + placebo with respect to event-free survival (EFS) per blinded independent central review (BICR) in participants with ESCC, in participants whose tumors express PD-L1 CPS =10, and in all participants<br> ;Secondary Objective: 1. To evaluate the safety and tolerability profile of dCRT + pembrolizumab;<br> Primary end point(s): 1. Overall Survival (OS)<br> 2. Event-free Survival (EFS)<br> ;<br> Timepoint(s) of evaluation of this end point: 1. Up to ~72 months<br> 2. Up to ~60 months<br>
- Secondary Outcome Measures
Name Time Method <br> Secondary end point(s): 1. Number of participants with an adverse event (AE)<br> 2. Number of participants discontinuing study treatment due to an AE<br> ;<br> Timepoint(s) of evaluation of this end point: 1. Up to ~15 months<br> 2. Up to ~12 months<br>