JCOG2301: A randomized controlled trial comparing conversion surgery with palliative chemotherapy in patients with initially unresectable cStage IVB/pStage IV advanced gastric cancer who presented remarkable response to chemotherapy

JRCT ID: jRCTs031240340

Registered date:17/09/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Initially unresectable gastric cancer, later resectable after a remarkable response to chemotherapy
• Date of first enrollment: 17/09/2024
• Target sample size: 126
• Study type: Interventional

Intervention(s)

Arm A: Continuation of first-line chemotherapy administered before registration
Arm B: conversion surgery with R0 resection followed by adjuvant chemotherapy with S-1 plus Oxaliplatin (SOX) or Capecitabine plus Oxaliplatin (CapeOX), or conversion surgery with non-resection or R1/R2 resection followed by postoperative chemotherapy with continuous first-line chemotherapy

Outcome(s)

• Primary Outcome: Overall survival
• Secondary Outcome: Event-free survival, progression-free survival, relapse-free survival, pathological response rate, R0 resection rate, chemotherapy continuation rate, chemotherapy dose intensity, adverse events

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 79age old
• Gender: Both

Include criteria

(1) Histologically proven adenocarcinoma of the stomach.
(2) No esophageal invasion or esophageal invasion within 3 cm prior to chemotherapy.
(3) Diagnosed as cStage IVB or pStage IV, with fulfillment of any of the following (i) to (iii) regarding distant metastasis before chemotherapy.
(i) Unresectable liver metastasis: more than 3 liver metastases on Gd-EOB-enhanced MRI.
(ii) Unresectable distant lymph node metastasis: distant lymph node metastasis excluding para-aortic lymph node No.16a2/16b1 on enhanced CT.
(iii) Unresectable peritoneal dissemination: meeting any of the following (a) to (d).
(a) Peritoneal nodules or findings indicative of peritoneal dissemination on enhanced CT, such as ascites beyond the pelvic cavity, hydronephrosis, increased density of peritoneal fat tissue, and thickening of the intestinal wall.
(b) Stenosis or deformation of the intestinal wall in the small and large intestine on CT colonography or digestive tract contract inspection.
(c) P1b or P1c by laparotomy or laparoscopy
(4) Undergoing first-line chemotherapy with SOX, CapeOX or FOLFOX, regardless of the use of nivolumab in HER2-negative cases and trastuzumab in HER2-positive cases.
(5) No second- or later-line systemic chemotherapy.
(6) No progression of the primary lesion, regional lymph nodes, and distant metastases, and no new distant metastases.
(7) Confirmed P0 or resectable P1a by laparoscopy or laparotomy, and CY0 in peritoneal lavage cytology. Intra-abdominal observation and peritoneal lavage cytology are not mandatory in case of following (i) or (ii).
(i) T3 or shallower tumor depth before chemotherapy on enhanced CT (no serosal invasion).
(ii) T4 or deeper tumor depth before chemotherapy with only liver metastasis.
(8) Any of following (i) to (v) are fulfilled before registration in cases that had each distant metastasis before chemotherapy.
(i) Liver metastasis: three or fewer resectable liver metastases on Gd-EOB-enhanced MRI confirmed resectable within Makuuchi criteria assessed by ICG test.
(ii) Distant lymph node metastasis: all positive metastatic lymph nodes before chemotherapy have decreased to a long axis of less than 6 mm excluding No.16a2/b1 and confirmed resectable.
(iii) Ovarian metastasis: judged that curative resection is possible.
(iv) Adrenal metastasis: judged that curative resection is possible regarding left adrenal metastasis. Remnant right adrenal metastasis is not allowed.
(v) Distant metastasis other than peritoneal dissemination, liver metastasis, distant lymph node metastasis, ovarian metastasis, and adrenal metastasis: disappearance of all distant metastases seen before chemotherapy .
(9) Confirmation of meeting all criteria (6) to (8) for distant metastasis within 28 days from the last examination.
(10) Conduct of mismatch repair gene function testing.
(11) Judged that curative resection is possible.
(12) No prior endoscopic resection, surgery, or radiotherapy against the primary lesion, regional lymph nodes, and distant metastases except for bypass surgery for gastrointestinal obstruction.
(13) Sufficient oral intake.
(14) Not a remnant gastric cancer .
(15) No recurrent gastric cancer.
(16) No prior radiotherapy to the upper abdominal against any other malignancies.
(17) No history of systemic therapy including endocrine therapy, chemotherapy, molecular targeted therapy, and immunotherapy for any other cancers within 5 years.
(18) Aged 18 to 79 years old at registration.
(19) ECOG Performance status is 0 or 1.
(20) Sufficient organ function.
(i) Neutrophil >= 1,200/mm3
(ii) Hb >= 8.0 g/dL
(iii) Platelet >= 75,000/mm3
(iv) T.Bil <= 2.0 mg/dL
(v) AST <= 100 U/L
(vi) ALT <= 100 U/L
(vii) CCr >= 40 mL/min
(21) Written informed consent from patient.

Exclude criteria

(1) Synchronous or metachronous (within 5 years) malignancies.
(2) Infectious disease requiring systemic treatment.
(3) Body temperature of 38 degrees Celsius or higher.
(4) Female during pregnancy, within 28 days of postparturition, or during lactation. Males with partners planning conception shortly.
(5) Severe psychological disorder difficult to participate in this clinical study.
(6) Receiving continuous systemic corticosteroid with a prednisolone equivalent greater than 5 mg/day or immunosuppressant treatment.
(7) Under treatment with flucytosine.
(8) Unstable angina pectoris, or history of myocardial infarction within 6 months.
(9) Uncontrollable valvular heart disease, dilated cardiomyopathy, or hypertrophic cardiomyopathy.
(10) Uncontrollable hypertension.
(11) Uncontrollable diabetes mellitus.
(12) Pulmonary fibrosis or severe pulmonary emphysema based on chest CT.

Related Information

• Primary Sponsor: YOSHIKAWA Takaki
• Source(s) of Monetary Support: National Cancer Center Japan