Clinical Trials List
Protocol NumberD910GC00001
NCT Number(ClinicalTrials.gov Identfier)NCT04592913
Active
2020-10-26 - 2029-12-31
Phase III
Not yet recruiting5
Recruiting2
ICD-10C16.9
Malignant neoplasm of stomach, unspecified
ICD-10C7A.092
Malignant carcinoid tumor of the stomach
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9151.9
Malignant neoplasm of stomach, unspecified
A Randomized, Double-blind, Placebo-controlled, Phase III Study of Neoadjuvant-Adjuvant Durvalumab and FLOT Chemotherapy Followed by Adjuvant Durvalumab in Patients With Resectable Gastric and Gastroesophageal Junction Cancer (GC/GEJC)
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Trial Applicant
-
Sponsor
AstraZeneca
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Rheun-Chuan Lee 無
- 方文良 無
- San-Chi Chen 無
- 黃國宏 無
- Chung-Pin Li 無
- Yun-Cheng Hsieh 無
- Chien-An Liu 無
- Yee Chao 無
- Yi-Ping Hung 無
- Shao-Jung Hsu 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Wen-Chi Shen 無
- 黃文冠 無
- 劉耿豪 無
- 吳仁欽 無
- Tsai-Sheng Yang 無
- Po-Jung Su 無
- Tai-Sen Yeh 無
- 李兆偉 無
- Hung-Chih Hsu 無
- Ming-Mo Hou 無
- 徐潤德 無
- 曾振輝 無
- Wen-Chi Chou 無
- Yung-Chia Kao 無
- Chun-Nan Yeh 無
- 蔡駿逸 無
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- Chang-Fang Chiu 無
- 葉俊杰 Division of General Surgery
- 陳德鴻 無
- 楊宏仁 無
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- Chih-Hung Hsu 無
- TA-CHEN HUANG 無
- JHE-CYUAN GUO 無
- TSUNG-HAO LIU 無
- 楊博仁 無
- Chiun Hsu 無
- 呂理駿 無
- 梁逸歆 無
- I-RUE LAI 無
- MING-TSAN LIN 無
- Ann-Lii Cheng 無
- 張端瑩 無
- 陳國興 無
- 郭弘揚 未分科
- 李柏居 無
- 蔡佳惠 無
- 林宗哲 無
- YU-YUN SHAO 無
- Hsiang-Fong Kao 無
- 陳炯年 無
- Ying-Chun Shen 無
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Co-Principal Investigator
- Chia-Jui Yen 無
- 劉奕廷 無
- 趙盈瑞 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
esectable Gastric and Gastroesophageal Junction Cancer (GC/GEJC)
Objectives
T[Primary objective]
To compare Arm A relative to Arm B on event-free survival (EFS)
[Key secondary objectives]
●To compare Arm A relative to Arm B on overall survival (OS)
●To compare Arm A relative to Arm B on pathological complete response (pCR) rate
[Secondary objectives]
●To compare Arm A relative to Arm B on the proportion of patients who undergo gastrectomy or gastroesophagectomy
●To compare Arm A relative to Arm B on the rate of complete resection (R0)
●To compare Arm A relative to Arm B on metastasis-free survival (MFS) and disease-specific survival (DSS)
●To compare Arm A relative to Arm B on disease-free survival (DFS) in patients who undergo R0 resection surgery
●To compare Arm A relative to Arm B on EFS24, EFS36, OS24, OS36, DFS24, and DFS36
●To compare Arm A relative to Arm B on efficacy endpoints by PD-L1 expression
●To compare Arm A relative to Arm B on disease-related symptoms, impacts, and HRQoL
●To evaluate the PK of Arm A and Arm B
●To assess the immunogenicity of Arm A and Arm B
[Safety objective]
To assess the safety and tolerability of Arm A as compared to Arm B in subjects with GC/GEJC
Test Drug
Durvalumab
Active Ingredient
Durvalumab
Dosage Form
injection
Dosage
50 mg/ml
Endpoints
To compare Arm A relative to Arm B on event-free survival (EFS)
Inclution Criteria
1 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.
2 Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
3 Age ≥18 years at the time of screening. For patients aged <20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative.
4 Histologically documented gastric or gastroesophageal junction adenocarcinoma with resectable disease (ie, radical-surgery eligible; Stage II or higher [>T2 N0-3 M0 or T0-4 N1-3 M0] per AJCC 8th edition). GEJC includes Siewert* type 2 and 3 tumor. Siewert* type 1 tumor is also eligible as long as the patient is intended to be treated in the same way as for Siewert type 2 and 3 tumors.
(a) Per the judgment of the Investigator, patient must be medically fit for treatment with neoadjuvant FLOT therapy prior to radical surgery.
(b) 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 (see Section 6.1.3 regarding surgical plan).
(c) No prior anti-cancer therapy (eg, chemotherapy, radiation therapy, or chemoradiation therapy) for the current malignancy.
*Siewert classification
· Siewert Type 1: adenocarcinoma of the lower esophagus with the center located within 1 cm to 5 cm above the anatomic GEJ.
· Siewert Type 2: true carcinoma of the cardia at the GEJ, with the tumor center within 1 cm above and 2 cm below the GEJ.
· Siewert Type 3: subcardial carcinoma with the tumor center between 2 and 5 cm below GEJ, which infiltrates the GEJ and lower esophagus from below.
5 World Health Organization (WHO)/ECOG performance status (PS) of 0 or 1 at enrollment
6 Adequate organ and marrow function as defined below:
(a) Hemoglobin ≥9.0 g/dL
(b) Absolute neutrophil count ≥1.5 × 10^9 /L
(c) Platelet count ≥100 × 10^9/L
(d) Serum bilirubin ≤1.5 × the upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome, who will be allowed in consultation with their physician.
(e) ALT and AST ≤2.5 × ULN
(f) Measured creatinine clearance (CL) >50 mL/min or Calculated creatinine clearance (CL) >50 mL/min as determined by Cockcroft-Gault (using actual body weight)
Males: Creatinine CL (mL/min)= [Wight (kg) × (140 - Age)]/[72 × serum creatinine (mg/dL)]
Females: Creatinine CL (mL/min)= [Wight (kg) × (140 - Age)]/[72 × serum creatinine (mg/dL)] × 0.85
7 Must have a life expectancy of at least 24 weeks
8 Body weight >30 kg at enrollment and randomization
9 Male and/or female
10 Tumor PD-L1 status, confirmed by a reference laboratory using the Ventana SP263 PD‑L1 IHC assay, must be known prior to randomization. As such, all patients must be able to undergo a new tumor biopsy during screening or to provide an available tumor sample taken <3 months prior to enrollment. The tumor specimen submitted to establish eligibility should be of sufficient quantity to allow for PD-L1 IHC and other exploratory biomarker analyses and is preferred in formalin-fixed paraffin embedded blocks. (Refer to Section 8.5.1 for information regarding obtaining tumoral PD-L1 status prior to the 28‑day screening window.)
2 Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
3 Age ≥18 years at the time of screening. For patients aged <20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative.
4 Histologically documented gastric or gastroesophageal junction adenocarcinoma with resectable disease (ie, radical-surgery eligible; Stage II or higher [>T2 N0-3 M0 or T0-4 N1-3 M0] per AJCC 8th edition). GEJC includes Siewert* type 2 and 3 tumor. Siewert* type 1 tumor is also eligible as long as the patient is intended to be treated in the same way as for Siewert type 2 and 3 tumors.
(a) Per the judgment of the Investigator, patient must be medically fit for treatment with neoadjuvant FLOT therapy prior to radical surgery.
(b) 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 (see Section 6.1.3 regarding surgical plan).
(c) No prior anti-cancer therapy (eg, chemotherapy, radiation therapy, or chemoradiation therapy) for the current malignancy.
*Siewert classification
· Siewert Type 1: adenocarcinoma of the lower esophagus with the center located within 1 cm to 5 cm above the anatomic GEJ.
· Siewert Type 2: true carcinoma of the cardia at the GEJ, with the tumor center within 1 cm above and 2 cm below the GEJ.
· Siewert Type 3: subcardial carcinoma with the tumor center between 2 and 5 cm below GEJ, which infiltrates the GEJ and lower esophagus from below.
5 World Health Organization (WHO)/ECOG performance status (PS) of 0 or 1 at enrollment
6 Adequate organ and marrow function as defined below:
(a) Hemoglobin ≥9.0 g/dL
(b) Absolute neutrophil count ≥1.5 × 10^9 /L
(c) Platelet count ≥100 × 10^9/L
(d) Serum bilirubin ≤1.5 × the upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome, who will be allowed in consultation with their physician.
(e) ALT and AST ≤2.5 × ULN
(f) Measured creatinine clearance (CL) >50 mL/min or Calculated creatinine clearance (CL) >50 mL/min as determined by Cockcroft-Gault (using actual body weight)
Males: Creatinine CL (mL/min)= [Wight (kg) × (140 - Age)]/[72 × serum creatinine (mg/dL)]
Females: Creatinine CL (mL/min)= [Wight (kg) × (140 - Age)]/[72 × serum creatinine (mg/dL)] × 0.85
7 Must have a life expectancy of at least 24 weeks
8 Body weight >30 kg at enrollment and randomization
9 Male and/or female
10 Tumor PD-L1 status, confirmed by a reference laboratory using the Ventana SP263 PD‑L1 IHC assay, must be known prior to randomization. As such, all patients must be able to undergo a new tumor biopsy during screening or to provide an available tumor sample taken <3 months prior to enrollment. The tumor specimen submitted to establish eligibility should be of sufficient quantity to allow for PD-L1 IHC and other exploratory biomarker analyses and is preferred in formalin-fixed paraffin embedded blocks. (Refer to Section 8.5.1 for information regarding obtaining tumoral PD-L1 status prior to the 28‑day screening window.)
Exclusion Criteria
1 Patients with peritoneal dissemination (including tumor cells in peritoneal fluid) or distant metastasis
2 Patients with adenosquamous cell carcinoma, squamous cell carcinoma, or GI stromal tumor
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], 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 (eg, 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 Sponsor
(e) Patients with celiac disease controlled by diet alone
5 Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease, serious chronic GI conditions associated with diarrhea, or psychiatric illness/social situations 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 ≥5 years before the first dose of IP 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), 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.
9 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).
10 Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
11 Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable.
12 Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
13 Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
14 Prior immune-mediated therapy including, but not limited to, other anti-cytotoxic T‑lymphocyte-associated antigen 4 (CTLA-4), anti-PD-1, anti-PD-L1, and anti‑programmed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines.
15 Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
(a) Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection)
(b) Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
(c) Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
16 Participation in another clinical study with an investigational product administered in the last 28 days
17 Previous IP assignment in the present study
18 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
19 Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment.
20 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/placebo monotherapy.
21 Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
2 Patients with adenosquamous cell carcinoma, squamous cell carcinoma, or GI stromal tumor
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], 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 (eg, 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 Sponsor
(e) Patients with celiac disease controlled by diet alone
5 Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease, serious chronic GI conditions associated with diarrhea, or psychiatric illness/social situations 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 ≥5 years before the first dose of IP 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), 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.
9 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).
10 Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
11 Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable.
12 Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP.
13 Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
14 Prior immune-mediated therapy including, but not limited to, other anti-cytotoxic T‑lymphocyte-associated antigen 4 (CTLA-4), anti-PD-1, anti-PD-L1, and anti‑programmed cell death ligand 2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines.
15 Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
(a) Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection)
(b) Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
(c) Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
16 Participation in another clinical study with an investigational product administered in the last 28 days
17 Previous IP assignment in the present study
18 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
19 Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment.
20 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/placebo monotherapy.
21 Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
The Estimated Number of Participants
-
Taiwan
42 participants
-
Global
900 participants
