eoadjuvant durvalumab (MEDI4736) plus docetaxel, oxaliplatin, S-1 (DOS) followed by surgery and adjuvant durvalumab plus S-1 chemotherapy in potentially resectable MMR proficient (pMMR) gastric or gastroesophageal junction (GEJ) adenocarcinoma
- Conditions
- Neoplasms
- Registration Number
- KCT0004390
- Lead Sponsor
- Asan Medical Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 68
•Newly diagnosed pathologically proven potentially resectable gastric or GEJ adenocarcinoma
•Clinical stages of T3–4N0 or T2–4N+ according to the American Joint Committee on Cancer (AJCC) 8th edition by computed tomography (CT)
•Microsatellite-instability (MSI) status determined by immunohistochemical (IHC) staining
•No peritoneal seeding identified by laparoscopy if suspected by CT
•Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations
•Age > 18 years at time of study entry
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
•Life expectancy of > 12 months
•Body weight > 30kg
•No existing neuropathy
•Adequate normal organ and marrow function as defined below:
-Haemoglobin =9.0 g/dL
-Absolute neutrophil count (ANC) 1.5 (or 1.0) x (> 1500 per mm3)
-Platelet count =100 (or 75) x 109/L (>75,000 per mm3)
-Serum bilirubin =1.5 x institutional upper limit of normal (ULN)
-AST (SGOT)/ALT (SGPT) =2.5 x institutional ULN
-Measured creatinine clearance (CL) > 40 mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
Males:
Creatinine CL (mL/min)=Weight (kg) x (140 – Age)
72 x serum creatinine (mg/dL)
Females:
Creatinine CL (mL/min)=Weight (kg) x (140 – Age) x 0.85
72 x serum creatinine (mg/dL)
•Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
-Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy)
-Women =50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
•Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
•Participation in another clinical study with an investigational product during the last 2 weeks
•Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
•Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable
•Major surgical procedure within 28 days prior to the first dose of durvalumab
•Distant metastasis including M1 lymph node
•Unable to take medication orally
•Gastric outlet obstruction and/or severe gastrointestinal bleeding
•Impaired bowel absorption, including any of the following:
-Bowel obstruction
-Chronic inflammatory bowel disease
-History of extended bowel resection
-Gastric dumping syndrome
•History of allogenic organ transplantation
•Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
a.Patients with vitiligo or alopecia
b.Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
c.Any chronic skin condition that does not require systemic therapy
d.Patients without active disease in the last 5 years may be included but only after consultation with the study physician
e.Patients with celiac disease controlled by diet alone
•Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events (AEs) or compromise the ability of the patient to give written informed consent
•History of another primary malignancy except for
a.Malignancy treated with curative intent and with no known active disease = 5 years before the first dose of durvalumab and of low potential risk for recurrence
b.Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
c.Adequately treated carcinoma in situ without evidence of disease
•Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) =470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart)
•History of active primary immunodeficiency
•Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
•Current or pri
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Pathologic complete regression (pCR) rate;Safety
- Secondary Outcome Measures
Name Time Method Disease free survival (DFS);R0 resection rate;Correlation of efficacy (pCR and DFS) with potential biomarkers including