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

NCT ID: NCT04999332

Last Updated: 2023-11-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

58 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-10

Study Completion Date

2025-12-31

Brief Summary

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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

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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.

Conditions

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Gastric Cancer Gastric Adenocarcinoma Effects of Chemotherapy Toxicity Due to Chemotherapy

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Single intervention arm with trial treatment
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Open-label

Study Groups

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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

Group Type EXPERIMENTAL

leucovorin, oxaliplatin, docetaxel, S-1

Intervention Type DRUG

Perioperative chemotherapy with LOTS

Interventions

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leucovorin, oxaliplatin, docetaxel, S-1

Perioperative chemotherapy with LOTS

Intervention Type DRUG

Other Intervention Names

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

Eligibility Criteria

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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.
Minimum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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TTY Biopharm

INDUSTRY

Sponsor Role collaborator

Kaohsiung Veterans General Hospital.

OTHER

Sponsor Role collaborator

Taipei Veterans General Hospital, Taiwan

OTHER_GOV

Sponsor Role collaborator

China Medical University Hospital

OTHER

Sponsor Role collaborator

National Cheng-Kung University Hospital

OTHER

Sponsor Role lead

Responsible Party

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YS Shan, MD, PhD

Professor, Dean of College of Medicine, National Cheng Kung University

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Chia Jui Yen, M.D., Ph.D.

Role: STUDY_CHAIR

Department of Oncology, National Cheng Kung University Hospital

Yan Shen Shan, M.D., Ph.D.

Role: STUDY_DIRECTOR

Department of Surgery, National Cheng Kung University Hospital

I Shu Chen, M.D.

Role: PRINCIPAL_INVESTIGATOR

Department of General Surgery, Kaohsiung Veterans General Hospital

Li Yuan Bai, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Department of Hematology/Oncology, China Medical University Hospital

Ming Huang Chen, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Department of Oncology, Taipei Veterans General Hospital

Locations

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Kaohsiung Veterans General Hospital

Kaohsiung City, , Taiwan

Site Status RECRUITING

China Medical University Hospital

Taichung, , Taiwan

Site Status NOT_YET_RECRUITING

National Cheng Kung University Hospital

Tainan City, , Taiwan

Site Status RECRUITING

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status NOT_YET_RECRUITING

Countries

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Taiwan

Central Contacts

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Clinical Trial Center, National Cheng-Kung University Hospital

Role: CONTACT

+886-6-2353535 ext. 4290

Chih Chieh Yen, M.D.

Role: CONTACT

+886-6-2353535 ext. 4620

Facility Contacts

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I Shu Chen, M.D.

Role: primary

+886-7-342-2121 ext. 73008

Li Yuan Bai, M.D., Ph.D.

Role: primary

+886-4-22053366 ext. 5051

Chih Chieh Yen, M.D.

Role: primary

+886-235-3535 ext. 4620

Ming Huang Chen, M.D., Ph.D.

Role: primary

+886-2-2875-7270

References

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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.

Reference Type RESULT
PMID: 16822992 (View on PubMed)

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.

Reference Type RESULT
PMID: 21444866 (View on PubMed)

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.

Reference Type RESULT
PMID: 30982686 (View on PubMed)

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.

Reference Type 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.

Reference Type RESULT
PMID: 31765987 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Other Identifiers

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LOTS-GC-01

Identifier Type: -

Identifier Source: org_study_id

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