Randomized, double-blind, phase II trial of adjuvant MEDI4736 or placebo for completely resected esophageal squamous cell carcinoma previously treated with neoadjuvant concurrent chemo-radiotherapy
- Conditions
- Neoplasms
- Registration Number
- KCT0004987
- Lead Sponsor
- Samsung Medical Center
- Brief Summary
Adjuvant durvalumab failed to improve survival after neoadjuvant CCRT in patients with ESCC. However, post-CCRT PD-L1 expression could predict the survival of patients who received adjuvant durvalumab after neoadjuvant CCRT, which need to be validate.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 86
(1) Patients with pathologically diagnosed squamous cell esophageal cancer (with or without PD-L1 expression)
(2) A person who has undergone concurrent chemotherapy before surgery and has undergone radical complete resection for esophageal cancer.
(3) After radical complete resection, at least 20 days have passed but 57 days have not passed (that is, registration is possible between 20 and 56 days after surgery based on the date of surgery)
(4) T3-4N0M0 or T1-4N1-3M0 surgical stage during diagnosis or after concurrent chemotherapy
(5) Those who have been diagnosed through endoscopic biopsy before concurrent chemotherapy and exist for exploratory research
(4 µm, 15 non-stained slides are required. The amount is determined at the discretion of the investigator, but at least prior to concurrent chemoradiotherapy, except when PD-L1 expression is not possible due to complete remission in surgical tissue. 1 piece of non-stained slide is required)
(6) Those who have sufficient organizations and agree to provide them
(A total of 15 slides are needed for cancer in the esophagus and lymph node metastasis, respectively. If there is a good response to concurrent chemotherapy and there is no cancer in the esophagus or lymph nodes, the slide will be made only in the area where the cancer is present. If, after simultaneous chemoradiotherapy, no cancer remains in the esophagus and lymph nodes through surgery, that is, registration is possible without tissue provision.)
(7) 5FU / CDDP (5-fluorouracil / cisplatin) of concurrent anticancer radiation therapy before surgery (4000mg / m2 for 4 days and 60mg / m2 D1 every 3 weeks) 2 anticancer chemotherapy and 44Gy / 22F radiotherapy Is recommended. (Currently, Samsung Medical Center's usual treatment regimen) However, this is not a mandatory requirement and can be registered if it is considered that concurrent chemotherapy has been sufficiently conducted at the discretion of the researcher. (In other words, therapy with paclitaxel / platinum drugs is also possible).
(8) Minimum amount of treatment for concurrent chemotherapy prior to surgery
-Anti-cancer chemotherapy: 100% dose of 1 cycle of each therapy (e.g. 5FU / CDDP 4000 mg / m2 and 60mg / m2)
-Radiation therapy: at least 40Gy
(9) 18 years or older
(10) ECOG 0-1
(11) Sufficient long-term function
Hb=9.0g / dl, ANC> 1.5 x 109 / L, PLT> 100 x 109 / L, total bilirubin =1.5 UNL documented Gilbert syndrome (=3 X ULN), AST and / or ALT <2.5 UNL, Cockcroft- Cleaning rate of creatinine by Gault formula =40mL / min [Men: Weight (kg) x (140-age) / (72x serum creatinine), Female: Weight (kg) x (140-age) x 0.85 / (72 x serum creatinine) )]
(12) A person who signed and dated the consent form prior to the implementation of the specific procedure for the clinical trial.
(13) Those who can comply with the scheduled follow-up and toxicity control procedures.
(14) Men / women of childbearing age who agreed to use effective contraception
(1) Participation in another clinical study with PD-1 or PD-L1 inhibitors at any time
(2) Any previous treatment with a PD-1, PD-L1 inhibitor or any anti-cancer therapy after complete resection of esophageal cancer
(3) Mean QT interval corrected for heart rate (QTc) =470 ms using Bazett’s correction
(4) Current or prior use of immunosuppressive medication within 14 days before the first dose of MEDI4736, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
(5) Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn’s disease], diverticulitis with the exception of diverticulosis, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), Graves’ disease, rheumatoid arthritis, hypophysitis, uveitis, etc within the past 3 years prior to the start of treatment. The following are exceptions to this criterion: Patients with vitiligo or alopecia, Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement or psoriasis not requiring systemic treatment
(6) History of primary immunodeficiency
(7) History of allogenic organ transplant
(8) History of hypersensitivity to MEDI4736
(9) Active infection of hepatitis B or hepatitis C.
- Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result.
- Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible.
- Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid (RNA).
? Reference : 2015 The Korean Association for the Study of the Liver, Chronic Hepatatis Clinical Practice Guideline
(10) Pregnant and lactating women
(11) If the examiner determines that there is a heart condition that interferes with the evaluation of the clinical trial drug or patient safety or interpretation of clinical trial results
(Eg,Uncontrolled symptomatic congestive heart failure or unstable angina, diabetes or arrhythmia present. Unregulated unstable angina is a condition in which symptoms continue to deteriorate after medical treatment such as medical treatment or coronary angioplasty. In such a case the decision whether to register is made at the discretion of the Investigator.)
(12) Those with evidence of active infection requiring active antibiotic treatment, including tuberculosis
(13) subject who are unable to conduct periodic follow-up due to psychological, social, family or geographical reasons
(14) Patients with serious and unstable medical and psychiatric conditions that may affect the subject's safety, consent submission, and compliance with the study
(15) Prior history of malignancy within 5 years from study entry except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer, or early gastric cancer. The incidentally detected, non-metastatic well differentiated thyroid cancer can be enrolled irrespective of the treatment, because the prognosis of this type of cancer is known much better than the study disease, even it is untreated. For the debatable double primary cancer, the enrolment can be di
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method disease-free survival
- Secondary Outcome Measures
Name Time Method Association between PD-L1 expression in tumors, disease-free survival, and overall survival;Analysis of changes in PD-L1 expression in tissues before and after concurrent chemotherapy;Difference analysis of PD-L1 expression pattern in primary tumor and lymph node metastasis;safety;overall survival