Perioperative Leucovorin, Oxaliplatin, Docetaxel and S-1 (LOTS) For Locally Advanced Gastric or Gastroesophageal Junction Cancer

Sponsor
National Cheng-Kung University Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT04999332
Collaborator
TTY Biopharm (Industry), Kaohsiung Veterans General Hospital. (Other), Taipei Veterans General Hospital, Taiwan (Other), China Medical University Hospital (Other)
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Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: leucovorin, oxaliplatin, docetaxel, S-1
Phase 2

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
58 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Intervention Model Description:
Single intervention arm with trial treatmentSingle intervention arm with trial treatment
Masking:
None (Open Label)
Masking Description:
Open-label
Primary Purpose:
Treatment
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
Actual Study Start Date :
Dec 10, 2021
Anticipated Primary Completion Date :
Dec 31, 2024
Anticipated Study Completion Date :
Dec 31, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Perioperative chemotherapy with LOTS

LOTS as one cycle: Leucovorin (30 mg) twice daily per oral, day 1 to 7; Oxaliplatin (85 mg per square meter) intravenously, day 1; Docetaxel (40 mg per square meter) intravenously, day 1; S-1 (35 mg per square meter) twice daily per oral, day 1 to 7 Pre-operative part: Four cycles of LOTS every two weeks Operative part: Curative gastrectomy or gastroesophagectomy plus D2 lymphadenectomy Post-operative part: Four cycles of LOTS every two weeks

Drug: leucovorin, oxaliplatin, docetaxel, S-1
Perioperative chemotherapy with LOTS
Other Names:
  • leucovorin (Folina tab, TTY Biopharm, TW)
  • oxaliplatin (Oxalip, TTY Biopharm, TW)
  • docetaxel (Taxotere, Sanofi-Aventis, FR)
  • S-1 (TS-1, Taiho, JP)
  • Outcome Measures

    Primary Outcome Measures

    1. Pathological response [after pre-operative chemotherapy and curative surgery (Week 11 to 13)]

      the tumor pathological response after pre-operative chemotherapy with LOTS plus curative surgery. The pathological response is defined by tumor evaluation of complete, partial or no response according to tumor regression grading (TRG)

    2. Curative resection rate [after pre-operative chemotherapy and curative surgery (Week 11 to 13)]

      the rate of margin-free (R0) resection in the absence of macro- or microscopic residual tumors remaining at the primary tumor bed

    Secondary Outcome Measures

    1. Recurrence-free survival [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]

      the time interval from the initiation of trial treatment to disease recurrence, progression or death at any causes

    2. Overall survival [From date of the initiation of trial treatment until the date of death at any causes, assessed up to 48 months]

      the time interval from the initiation of trial treatment to death at any causes

    3. Disease control rate [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]

      the rate of patients remaining in disease control (complete, partial response and stable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines version 1.1) lasting at least three months

    4. Protocol completion rate [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]

      the rate of patients completing the pre-specified protocol treatment

    5. Treatment-emergent adverse event rate [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]

      the rate of protocol treatment-emergent adverse events, as graded by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Kaohsiung Veterans General Hospital Kaohsiung Taiwan 813
    2 China Medical University Hospital Taichung Taiwan 404
    3 National Cheng Kung University Hospital Tainan Taiwan 704
    4 Taipei Veterans General Hospital Taipei Taiwan 112

    Sponsors and Collaborators

    • National Cheng-Kung University Hospital
    • TTY Biopharm
    • Kaohsiung Veterans General Hospital.
    • Taipei Veterans General Hospital, Taiwan
    • China Medical University Hospital

    Investigators

    • Study Chair: Chia Jui Yen, M.D., Ph.D., Department of Oncology, National Cheng Kung University Hospital
    • Study Director: Yan Shen Shan, M.D., Ph.D., Department of Surgery, National Cheng Kung University Hospital
    • Principal Investigator: I Shu Chen, M.D., Department of General Surgery, Kaohsiung Veterans General Hospital
    • Principal Investigator: Li Yuan Bai, M.D., Ph.D., Department of Hematology/Oncology, China Medical University Hospital
    • Principal Investigator: Ming Huang Chen, M.D., Ph.D., Department of Oncology, Taipei Veterans General Hospital

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    YS Shan, MD, PhD, Professor, Dean of College of Medicine, National Cheng Kung University, National Cheng-Kung University Hospital
    ClinicalTrials.gov Identifier:
    NCT04999332
    Other Study ID Numbers:
    • LOTS-GC-01
    First Posted:
    Aug 10, 2021
    Last Update Posted:
    May 27, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by YS Shan, MD, PhD, Professor, Dean of College of Medicine, National Cheng Kung University, National Cheng-Kung University Hospital
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of May 27, 2022