Trial of Neoadjuvant Durvalumab Plus Docetaxel Oxaliplatin S-1 Followed by Surgery and Adjuvant Durvalumab Plus S-1 Chemotherapy in Potentially Resectable MMR Proficient Gastric or Gastroesophageal Junction Adenocarcinoma

  • STATUS
    Recruiting
  • End date
    Jun 30, 2022
  • participants needed
    68
  • sponsor
    Asan Medical Center
Updated on 24 January 2021

Summary

Neoadjuvant 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

Description

  • Treatment for the main treatment group (pMMR tumor)
    1. Neoadjuvant treatment Durvalumab 1120 mg IV on day (D) 1, Docetaxel 50 mg/m2 intravenously (IV) on D1, oxaliplatin 100 mg/m2 IV on D1, S-1 40 mg/m2 bid orally on D1-14, will be administered every three weeks for three cycles.
    2. Surgery
    3. Adjuvant treatment After 4-6 weeks from surgery, S-1 40 mg/m2 bid orally on D1-28 plus durvalumab 1120 mg on D1 and D22 will be administered every 6 weeks for 12 months as an adjuvant treatment.
      • Treatment for the exploratory group (dMMR tumor)
    4. Neoadjuvant treatment Durvalumab 1500 mg IV and tremelimumab 75 mg IV on D1 will be administered every four weeks for three cycles.
    5. Surgery
    6. Adjuvant treatment After 4-6 weeks from surgery, durvalumab 1500 mg on D1 will be administered every 4 weeks for 12 months as an adjuvant treatment.

Details
Condition Resectable Gastric or Gastroesophageal Junction Adenocarcinoma
Treatment Durvalumab and Tremelimumab, Docetaxel, Oxaliplatin, S-1 and Durvalumab
Clinical Study IdentifierNCT04221555
SponsorAsan Medical Center
Last Modified on24 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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
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

Exclusion Criteria

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 replacementtherapy) 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
Patients with vitiligo or alopecia
Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
Any chronic skin condition that does not require systemic therapy
Patients without active disease in the last 5 years may be included but only after consultation with the study physician
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
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
Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
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 prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion
Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
Receipt of live attenuated vaccine within 30 days prior to the first dose of durvalumab. Note: Patients, if enrolled, should not receive live vaccine whilst receiving durvalumab and up to 30 days after the last dose of durvalumab
Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab
Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
Prior randomisation or treatment in a previous durvalumab or tremelimumab clinical study regardless of treatment arm assignment
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