Clinical trial NCT04999332: Perioperative Leucovorin, Oxaliplatin, Docetaxel and S-1 (LOTS) For Locally Advanced Gastric or Gastroesophageal Junction Cancer
Official title: A Phase II Trial of Perioperative Chemotherapy With Leucovorin, Oxaliplatin, Docetaxel and S-1 (LOTS) For Patients With Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Gastric Cancer
Gastric Adenocarcinoma
Effects of Chemotherapy
Toxicity Due to Chemotherapy
Keywords: Gastric cancer
Gastroesophageal junction cancer
Locally advanced
Perioperative chemotherapy
Triplet
Lead sponsor: National Cheng-Kung University Hospital
Sponsor class: OTHER
Collaborators: name: TTY Biopharm
name: Kaohsiung Veterans General Hospital.
name: Taipei Veterans General Hospital, Taiwan
name: China Medical University Hospital
First posted: 2021-08-10
Enrollment: 58
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single intervention arm with trial treatment
Primary purpose: TREATMENT

Brief summary: The aim of the trial is to investigate the clinical efficacy and toxicity of perioperative chemotherapy with leucovorin, oxaliplatin, docetaxel and S-1 (LOTS) in patients with locally advanced gastric or gastroesophageal junction adenocarcinoma who receive a curative surgery.

Detailed description: The study is an open-label, single-arm, single-country and multi-center phase II investigator-initiated trial. Patients with locally advanced gastric or gastroesophageal junction adenocarcinoma who enroll the trial will receive perioperative chemotherapy with LOTS (14 days as a cycle) 4 cycles every 2 weeks, followed by operation and another 4 cycles every 2 weeks post-operatively. The primary outcome is pathological response or curative resection rate. The secondary outcome includes recurrence-free survival, overall survival, disease control rate, protocol completion rate and adverse events.

Eligibility criteria: Inclusion Criteria:

1. Subjects have histologically-confirmed gastric or gastroesophageal junction (classified as Siewert type III) adenocarcinoma with a clinical stage of T3 or above, lymph node involvement (N+) or both according to American Joint Cancer Committee staging system, 8th edition (AJCC 8th).
2. Subjects present with at least one measurable lesion which can be accurately assessed by conventional techniques at least 2.0 cm or 1.0 cm by computed tomography (CT) or magnetic resonance imaging (MRI).
3. Subjects have a lymph node-positive disease in which that at least one of the nodes with a diameter greater or equal to 0.8 cm in the long axis. If subjects do not have a node-positive disease, a clinical stage of T3 or above and a measurable tumor is required for inclusion.
4. Subjects are above 20 years of age with an Eastern Cooperative Oncology Group (ECOG) performance status ≤1, have a life expectancy \>3 months, have surgically resectable disease and are physically competent and willing to receive a curative operation.
5. Subjects have adequate organ functions, including bone marrow reserve with a leukocyte count ≥3,000 /µL and platelet count ≥100,000 /µL, hepatic reserve with a serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 times of upper limits and total bilirubin ≤2.0 mg/dL, renal reserve with a creatinine clearance ≥60 mL/min and cardiac reserve with a left ventricular ejection fraction (LVEF) ≥50% by echocardiography at baseline.
6. Subjects have, or agree to establish a vascular access that permits systemic intravenous chemotherapy and are capable of ingesting capsules per oral.
7. Subjects with reproductive potentials are willing to accept contraceptive measures during the trial.
8. Subjects are functionally and cognitively capable to be informed of the trial contents and objectives (including obtaining blood and tumor tissue for the trial investigation), and agree to sign the written consent for enrollment.

Exclusion Criteria:

1. Subjects have metastatic (M1, including washing cytology positive for peritoneal carcinomatosis), recurrent gastric/gastroesophageal junction cancer (defined by an interval time less than five years from the current diagnosis to the prior initial disease), or any other underlying primary malignancies excluding carcinoma in situ or resectable skin cancer.
2. Subjects have received chemotherapies within 2 years, or a major abdominal surgery or radiotherapy within 4 weeks before the trial enrollment.
3. Subjects are known to be allergic to any of the studied chemotherapeutics.
4. Subjects have underlying chronic illnesses, including cardiopulmonary diseases, ischemic heart disease, inflammatory bowel disease, poorly-controlled diabetes mellitus, liver cirrhosis and/or peripheral neuropathy of any etiologies.
5. Subjects have active bacterial, viral, fungal or mycobacterial infections that require systemic therapy, including active infection with human immunodeficiency virus (HIV), hepatitis B or C virus (HBV or HCV)
6. Subjects are planning to conceive or already in pregnancy or breastfeeding.
7. Subjects are currently participating in any other clinical trials or studies.

Primary outcomes:
measure: Pathological response
timeFrame: after pre-operative chemotherapy and curative surgery (Week 11 to 13)
measure: Curative resection rate
timeFrame: after pre-operative chemotherapy and curative surgery (Week 11 to 13)
Secondary outcomes:
measure: Recurrence-free survival
timeFrame: From date of the initiation of trial treatment until the date of disease recurrence, progression or death at any causes, whichever came first, assessed up to 48 months
measure: Overall survival
timeFrame: From date of the initiation of trial treatment until the date of death at any causes, assessed up to 48 months
measure: Disease control rate
timeFrame: From date of the initiation of trial treatment until the date of recurrence/death events, withdrawal from the trial at any causes, termination/completion of the trial, whichever came first, assessed up to 48 months
measure: Protocol completion rate
timeFrame: From date of the initiation of trial treatment until the date of recurrence/death events, withdrawal from the trial at any causes, termination/completion of the trial, whichever came first, assessed up to 48 months
measure: Treatment-emergent adverse event rate
timeFrame: From date of the initiation of trial treatment until the date of recurrence/death events, withdrawal from the trial at any causes, termination/completion of the trial, whichever came first, assessed up to 48 months
Other outcomes:
Locations:
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Veterans General Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Department of Oncology, National Cheng Kung University Hospital
name: Chia Jui Yen, M.D., Ph.D.
role: STUDY_CHAIR
affiliation: Department of Surgery, National Cheng Kung University Hospital
name: Yan Shen Shan, M.D., Ph.D.
role: STUDY_DIRECTOR
affiliation: Department of General Surgery, Kaohsiung Veterans General Hospital
name: I Shu Chen, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Hematology/Oncology, China Medical University Hospital
name: Li Yuan Bai, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Oncology, Taipei Veterans General Hospital
name: Ming Huang Chen, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
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