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

Gastric Cancer Clinical Trial

— LOTS  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04999332
• Other study ID #: LOTS-GC-01
• Status: Recruiting
• Phase: Phase 2
• Start date: December 10, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: November 2023
• Source: National Cheng-Kung University Hospital
• Contact: Clinical Trial Center, National Cheng-Kung University Hospital
• Phone: +886-6-2353535
• Email: ctcnckuh[@]mail.hosp.ncku.edu.tw
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 58
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Effects of Chemotherapy
• Gastric Adenocarcinoma
• Gastric Cancer
• Stomach Neoplasms
• Toxicity Due to Chemotherapy

Intervention

Drug:
• leucovorin, oxaliplatin, docetaxel, S-1
Perioperative chemotherapy with LOTS

Locations

Country	Name	City	State
Taiwan	Kaohsiung Veterans General Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Taipei Veterans General Hospital	Taipei

Sponsors (5)

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

Country where clinical trial is conducted

Taiwan, 

References & Publications (5)

Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Pa — View Citation

Chiang NJ, Tsai KK, Hsiao CF, Yang SH, Hsiao HH, Shen WC, Hsu C, Lin YL, Chen JS, Shan YS, Chen LT. A multicenter, phase I/II trial of biweekly S-1, leucovorin, oxaliplatin and gemcitabine in metastatic pancreatic adenocarcinoma-TCOG T1211 study. Eur J Ca — View Citation

Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resect — View Citation

Kang YK, Yook JH, Park YK, et al. LBA41 - Phase III randomized study of neoadjuvant chemotherapy (CT) with docetaxel(D), oxaliplatin(O) and S-1(S) (DOS) followed by surgery and adjuvant S-1, vs surgery and adjuvant S-1, for resectable advanced gastric can

Ychou M, Boige V, Pignon JP, Conroy T, Bouche O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Geneve J, Lasser P, Rougier P. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLC — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological response	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)	after pre-operative chemotherapy and curative surgery (Week 11 to 13)
Primary	Curative resection rate	the rate of margin-free (R0) resection in the absence of macro- or microscopic residual tumors remaining at the primary tumor bed	after pre-operative chemotherapy and curative surgery (Week 11 to 13)
Secondary	Recurrence-free survival	the time interval from the initiation of trial treatment to disease recurrence, progression or death at any causes	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
Secondary	Overall survival	the time interval from the initiation of trial treatment to death at any causes	From date of the initiation of trial treatment until the date of death at any causes, assessed up to 48 months
Secondary	Disease control rate	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	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
Secondary	Protocol completion rate	the rate of patients completing the pre-specified protocol treatment	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
Secondary	Treatment-emergent adverse event rate	the rate of protocol treatment-emergent adverse events, as graded by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0	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