Gastric, Esophagogastric Junction
Conditions
Keywords
Durvalumab, FLOT chemotherapy
Brief summary
This study aims to assess the efficacy and safety of neoadjuvant adjuvant treatment with durvalumab in combination with FLOT compared to placebo in combination with FLOT in Chinese patients with Resectable Gastric and Gastroesophageal Cancer (GC/GEJC) (MATTERHORN-CN).
Detailed description
Informed by the favorable benefit-risk profile demonstrated by the global MATTERHORN study, the current study is designed to assess the efficacy and safety of neoadjuvant-adjuvant durvalumab in combination with FLOT chemotherapy followed by adjuvant durvalumab monotherapy (Arm A), compared with neoadjuvant-adjuvant placebo in combination with FLOT chemotherapy followed by adjuvant placebo monotherapy (Arm B) in Chinese participants with resectable GC/GEJC. Approximately 140 participants will be randomized to either Arm A or Arm B.
Interventions
A combination treatment made up of flurouroacil + leucovorin + oxaliplatin + docetaxel
DRUGDurvalumab
Human monoclonal antibody
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Capable of giving signed informed consent. 2. Male and/or Female, Age ≥ 18 years at the time of screening. 3. Histologically documented gastric or gastroesophageal junction adenocarcinoma with resectable disease, GEJC includes Siewert\* type 2 and 3 tumour and Siewert\* type 1 tumour. 1. Per the judgment of the Investigator, participants must be medically fit for treatment with neoadjuvant FLOT therapy prior to radical surgery. 2. At screening, complete surgical resection of the primary GC/GEJC must be deemed achievable, as assessed by a multidisciplinary evaluation, which must include a board certified GI surgeon. 3. No prior anti-cancer therapy (eg, chemotherapy, radiation therapy, or chemoradiation therapy) for the current malignancy. 4\. ECOG PS of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline at screening and prior to randomization. 5\. Adequate organ and marrow function as defined below: <!-- --> 1. Haemoglobin ≥ 9.0 g/dL 2. Absolute neutrophil count ≥ 1.5 × 109/L 3. Platelet count ≥ 100 × 109/L 4. Serum bilirubin ≤ 1.5 ×ULN. This will not apply to participants with confirmed Gilbert's syndrome, who will be allowed in consultation with their physician. 5. ALT and AST ≤ 2.5 × ULN 6. Measured CL \> 50 mL/min or Calculated CL \> 50 mL/min as determined by Cockcroft-Gault (using actual body weight) 6. Must have a life expectancy of at least 24 weeks. 7. Body weight \> 30 kg at enrolment and randomization. 8. Meeting tumour sample requirements (at screening) to confirm PD-L1 status.
Exclusion criteria
* -1. Participants with peritoneal dissemination (including tumour cells in peritoneal fluid) or distant metastasis. 2\. Participants with adenosquamous cell carcinoma, squamous cell carcinoma, or GI stromal tumour. 3\. History of allogeneic organ transplantation. 4. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], systemic lupus erythematosus, sarcoidosis, granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc), autoimmune pneumonitis, and autoimmune myocarditis. 5\. Uncontrolled intercurrent illness that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent. 6\. History of another primary malignancy except for (a) Malignancy treated with curative intent and with no known active disease ≥ 2 years before the first dose of study intervention 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 7. History of active primary immunodeficiency. 8. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice) and HIV verified by positive HIV-1 or HIV-2 antibodies. 9\. Mean QTc ≥ 470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart). 10\. Known allergy or hypersensitivity to any of the study interventions or any of the study intervention excipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To compare Arm A relative to Arm B on pCR rate | Up to 24 months after the last participant is randomized | pCR rate is defined as the proportion of participants who have no residual viable tumour in the resected specimens and as determined by central pathology review. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To compare Arm A relative to Arm B on event-free survival at 24 months (EFS24) | Up to 24 months after the last participant is randomized | EFS24 is the proportion of participants alive and event free 24 months after randomization, according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 per Investigator assessment and/or locally by pathology testing. |
| To compare Arm A relative to Arm B on overall survival (OS) | Up to 24 months after the last participant is randomized | Overall survival is length of time from randomization until the date of death due to any cause. |
| To compare Arm A relative to Arm B on event-free survival (EFS) | Up to 24 months after the last participant is randomized | EFS is defined as the time from randomization to the following, according to RECIST 1.1 per Investigator assessment and/or locally by pathology testing: 1. Progression that precludes surgery or requires non-protocol therapy, 2. Local or distant recurrence or progression of disease, or 3) Death due to any cause. |
| To compare Arm A relative to Arm B on the rate of complete resection (R0) | Up to 24 months after the last participant is randomized | R0 resection (complete resection) rate is the proportion of participants who have a confirmed complete resection as assessed by pathology review. |
| To compare Arm A relative to Arm B on metastasis-free survival (MFS) and disease-specific survival (DSS) | Up to 24 months after the last participant is randomized | MFS is the time from randomization until the development of metastasis using RECIST 1.1 or death due to any cause. • DSS is the time from randomization untildeath due to GC/GEJC. |
| To compare Arm A relative to Arm B on disease-free survival (DFS) in participants who undergo R0 resection surgery | Up to 24 months after the last participant is randomized | DFS is defined as the time from first post-surgery scan until disease recurrence, using RECIST 1.1, or death due to any cause. |
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed