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

NCT04999332 | Unknown Phase 2 DMC

• 1 other identifier: LOTS-GC-01
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 4

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.

Conditions

Gastric Cancer; Gastric Adenocarcinoma; Effects of Chemotherapy; Toxicity Due to Chemotherapy

Keywords

Gastric cancer; Gastroesophageal junction cancer; Locally advanced; Perioperative chemotherapy; Triplet

Outcome Measures

Primary Outcomes (2)

• 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)

• 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 Outcomes (5)

• 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

• Overall survival

  From date of the initiation of trial treatment until the date of death at any causes, assessed up to 48 months

• 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

• 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

• 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

Study Arms (1)

Perioperative chemotherapy with LOTS

EXPERIMENTAL

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

Interventions

leucovorin, oxaliplatin, docetaxel, S-1 DRUG

Perioperative chemotherapy with LOTS

Also known as: leucovorin (Folina tab, TTY Biopharm, TW), oxaliplatin (Oxalip, TTY Biopharm, TW), docetaxel (Taxotere, Sanofi-Aventis, FR), S-1 (TS-1, Taiho, JP)

Perioperative chemotherapy with LOTS

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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).
• 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.
• 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.
• Subjects have, or agree to establish a vascular access that permits systemic intravenous chemotherapy and are capable of ingesting capsules per oral.
• Subjects with reproductive potentials are willing to accept contraceptive measures during the trial.
• 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.

You may not qualify if:

• 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.
• Subjects have received chemotherapies within 2 years, or a major abdominal surgery or radiotherapy within 4 weeks before the trial enrollment.
• Subjects are known to be allergic to any of the studied chemotherapeutics.
• 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.
• 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)
• Subjects are planning to conceive or already in pregnancy or breastfeeding.
• Subjects are currently participating in any other clinical trials or studies.

Sponsors & Collaborators

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

Study Sites (4)

Kaohsiung Veterans General Hospital

Kaohsiung City, 813, Taiwan

RECRUITING

China Medical University Hospital

Taichung, 404, Taiwan

NOT YET RECRUITING

National Cheng Kung University Hospital

Tainan, 704, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, 112, Taiwan

NOT YET RECRUITING

Related Publications (5)

• 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 resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. doi: 10.1056/NEJMoa055531.

  PMID: 16822992 RESULT

• 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 FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. doi: 10.1200/JCO.2010.33.0597. Epub 2011 Mar 28.

  PMID: 21444866 RESULT

• 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-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Lohr C, Bernhard H, Schuch G, Rethwisch V, von Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Weniger J, Belle S, Gaiser T, Oduncu FS, Guntner M, Hozaeel W, Reichart A, Jager E, Kraus T, Monig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; FLOT4-AIO Investigators. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. 2019 May 11;393(10184):1948-1957. doi: 10.1016/S0140-6736(18)32557-1. Epub 2019 Apr 11.

  PMID: 30982686 RESULT

• 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 cancer (GC) (PRODIGY). Annals of Oncology. 2019 2019/10/01/;30:v876-v877.

  RESULT

• 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 Cancer. 2020 Jan;124:123-130. doi: 10.1016/j.ejca.2019.10.023. Epub 2019 Nov 22.

  PMID: 31765987 RESULT

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Leucovorin; Oxaliplatin; Docetaxel; S 1 (combination); titanium silicide

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Chia Jui Yen, M.D., Ph.D.

  Department of Oncology, National Cheng Kung University Hospital

  STUDY CHAIR

• Yan Shen Shan, M.D., Ph.D.

  Department of Surgery, National Cheng Kung University Hospital

  STUDY DIRECTOR

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trial Center, National Cheng-Kung University Hospital

CONTACT

+886-6-2353535; ctcnckuh@mail.hosp.ncku.edu.tw

Chih Chieh Yen, M.D.

CONTACT

+886-6-2353535; jack7481@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Open-label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Dean of College of Medicine, National Cheng Kung University

Model Details: Single intervention arm with trial treatment

Study Record Dates

• First Submitted: July 8, 2021
• First Posted: August 10, 2021
• Study Start: December 10, 2021
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2025
• Last Updated: November 15, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Upon publication of the data to a duration of ten years
• Access Criteria: Upon a formal request to the trial chairperson or chief principal investigator

Locations

TW (4)