Unresectable, Locally Advanced or Metastatic, Adenocarcinoma of the Stomach, or of the Gastro Esophageal JunctionPhase 2MATEONCT02128243

Trial of S-1 Maintenance Therapy in Metastatic Esophagogastric Cancer

A Phase 2 study testing S-1 de-escalation and Chemotherapy by Investigator's choice in people with Unresectable, Locally Advanced or Metastatic, Adenocarcinoma of the Stomach, or of the Gastro Esophageal Junction and Gastric Neoplasm, run by AIO-Studien-gGmbH at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The aim is to assess the relative efficacy of S-1 de-escalation therapy vs. continuation of chemotherapy after induction therapy in patients with metastatic esophagogastric cancer in terms of overall survival. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Unresectable, Locally Advanced or Metastatic, Adenocarcinoma of the Stomach, or of the Gastro Esophageal Junction, Gastric Neoplasm, Gastroesophageal Junction Adenocarcinoma
What is being tested?: S-1 de-escalation and Chemotherapy by Investigator's choice
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 242 participants
Where: 1 siteGermany
Study dates: Sep 2014to 8 Oct 2020
Phase: Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Signed written informed consent incl. participation in translational research
Male or female patient 18 years or older
Histologically confirmed metastatic or locally advanced unresectable gastric adenocarcinoma or adenocarcinoma of the esophagus or the esophagogastric junction (Her-2/neu negative or with unknown Her-2/neu status)
Adjuvant/neoadjuvant or perioperative chemotherapy or (chemo-)radiotherapy must have been finished at least 6 months before start of the induction therapy
For patients enrolled before induction therapy: No previous systemic treatment (i.e. chemotherapy) for metastatic disease
For patients enrolled after induction therapy: Having finished a three-months induction therapy (6 cycles of a bi-weekly regimen, 4 cycles of a three-weekly regimens or 3 cycles of a four-weekly regimen) without tumor progression or limiting toxicity

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ECOG Performance Score 0-1 (Karnofsky Performance status >= 80%)
Ability for oral intake of the study drug, patients with tumor-related problems with oral intake might be registered if the symptom is expected to be improved during induction therapy (e.g. due to a tumor stenosis)
Female patient of childbearing potential (i.e. did not undergo surgical sterilization - hysterectomy, bilateral tubal ligation, or bilateral oophorectomy - and is not post-menopausal for at least 24 consecutive months) with a negative pregnancy test
Hematology and biochemistry laboratory results within the limits normally expected for the patient population, defined by the following:
Absolute neutrophil count ≥ 1500/µl
Platelet count ≥ 100000/µl
Leukocyte count > 3000/µl
Hemoglobin ≥ 9 g/dL or 5.59 mmol/l, previous transfusions (>3 days) of erythrocytes are allowed
Total bilirubin ≤ 1.5 times the upper limit of normal (ULN), in patients with known Meulengracht syndrom ≤3 x ULN
AST ≤ 3xULN in absence of liver metastases, or ≤5xULN in presence of liver metastases
ALT ≤ 3xULN in absence of liver metastases, or ≤5xULN in presence of liver metastases
Creatinine clearance ≥30 mL/min according to Cockcroft-Gault formula

Who cannot join

Previous major sugery within the last 28 days before the start of the induction treatment. The implantation of a central venous access (e.g. porth-a cath system) is allowed.
History of other malignant tumors within the last 5 years before start of induction treatment, except basal cell carcinoma or curatively excised cervical carcinoma in situ
Known brain metastases
Concurrent radiotherapy involving target lesions used for this study. Concurrent palliative radiation for non-target lesions is allowed if other target lesions are available outside the involved field; previous radiotherapy including target lesions must have been finished at least 28 days before start of induction treatment.
For patients enrolled before the induction therapy: Previous systemic treatment (i.e. chemotherapy) for metastatic disease
Known active HBV, HCV infection or documented HIV infection

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Serious concomitant disease or medical condition that by judgment of the Investigator renders the patient at high risk of treatment complications
Clinically relevant coronary artery disease (NYHA functional angina classification III/IV), congestive heart failure (NYHA III/IV), clinically relevant cardiomyopathy, history of myocardial infarction in the last 3 months, or high risk of uncontrolled arrhythmia
Female patient pregnant or breast feeding
Female patient of childbearing potential (i.e. did not undergo surgical sterilization - hysterectomy, bilateral tubal ligation, or bilateral oophorectomy - and is not post-menopausal for at least 24 consecutive months) not willing to use an adequate method of contraception to avoid pregnancy throughout the study and for up to 26 weeks after the end of treatment. Male patient not willing to use an adequate method of contraception to avoid conception throughout the study and for up to 26 weeks after the end of treatment in such a manner that the risk of pregnancy is minimized.
Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 60 days prior to start of induction (e.g. one of the allowed standard chemotherapies (see above) with or without additional placebo within a clinical trial is allowed)
Chronic diarrhea or short bowel syndrome
Known hypersensitivity to S-1, other fluoropyrimidines or platinum compounds. Contraindication to receive S-1 or the polychemotherapy (induction \& arm B) chosen for this patient as per current Summary of Product Characteristics. Known DPD deficiency
For patients enrolled before the induction therapy: Grade ≥2 peripheral neuropathy
Known drug abuse/alcohol abuse

Trial locations and contacts

1 site in 1 country.

Germany1 site

NCT-Med. Onkologie
Heidelberg, Baden-Wurttemberg, 69120

Other trials in Germany

About this study

Official title: Randomized Controlled Trial of S-1 Maintenance Therapy in Metastatic Esophagogastric Cancer

Read the detailed description

Open-label, multi-center, controlled, randomized, parallel-group phase II trial in patients with metastatic esophagogastric cancer having received induction chemotherapy.

Patients will be registered before or after application of a three-months induction chemotherapy . This 12-week induction therapy will consist of one of the following regimens: FLO/mod. Folfox-6, Cisplatin/5-FU, Cisplatin/S-1, FLOT, EOX/EOF or XP. Regarding dose adjustments, Investigators should refer to Section 6.3 and to the summary of product characteristics of the chemotherapeutical agents. Patients having finished the preplanned induction therapy without tumor progression (i.e. with complete remission (CR), partial remission (PR), stable disease (SD) or non-CR/non-PD in patients with non-measurable disease only according to RECIST Criteria Version 1.1) at week 12, being able to swallow capsules and having Eastern Cooperative Oncology Group (ECOG) performance score of 0-1 will be randomized in a 2:1 ratio to receive Arm A or B.

In Arm A patients will continue with S-1 de-escalation phase starting at week 13 until disease progression, toxicities requiring discontinuation, withdrawal of consent, pregnancy, death or lost to follow up whichever occurs first. In patients with drug-related severe toxicity S-1 dose will be adjusted or study treatment will be terminated.

In Arm B patients will continue to receive the same polychemotherapy as during induction therapy until tumor progression, toxicities requiring discontinuation, withdrawal of consent, pregnancy, death or loss to follow up whichever occurs first.

Conditions: Unresectable, Locally Advanced or Metastatic, Adenocarcinoma of the Stomach, or of the Gastro Esophageal Junction, Gastric Neoplasm, Gastroesophageal Junction Adenocarcinoma, Esophageal Adenocarcinoma, Gastric Adenocarcinoma, Esophageal Neoplasms
Being tested: S-1 de-escalation, Chemotherapy by Investigator's choice
Medical subject headings: Neoplasm Metastasis, Stomach Neoplasms, Adenocarcinoma Of Esophagus, Esophageal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

S-1 de-escalationDrug
Also called Teysuno
S-1 30 mg/m² bid d1-14 q21d
Chemotherapy by Investigator's choiceDrug
Also called FLO regimen, - Oxaliplatin 85 mg/m², - Leucovorin 200 mg/m², - 5-Fluorouracil 2600 mg/m²
Polychemotherapy administration as in induction therapy consists of a platinum and fluoropyrimidine compound as well as optional a taxane / an anthracycline compound.
Two-Drug combinations:
FLO / mod. FOLFOX-6; Cisplatin, S-1; Cisplatin, 5-FU; Cisplatin, Capecitabine (XP)
Three-drug combinations:
EOX/EOF FLOT

Study groups in NCT02128243
Study group	Role	What they receive
Arm A: De-escalation therapy	Experimental	Patients in Arm A will continue with S-1 de-escalation phase starting at week 13 until disease progression, toxicities requiring discontinuation, withdrawal of consent, pregnancy, death or lost to follow up whichever occurs first. In patients with drug-related severe toxicity S-1 dose will be adjusted or study treatment will be terminated. Receives: Drug: S-1 de-escalation
Arm B: Chemotherapy by Investigator's choice	Experimental	Patients in Arm B will continue to receive the same polychemotherapy as during induction therapy until tumor progression, toxicities requiring discontinuation, withdrawal of consent, pregnancy, death or loss to follow up whichever occurs first. Receives: Drug: Chemotherapy by Investigator's choice

What is being measured

The primary outcome is the main question the study is designed to answer.

Overall Survival (OS)
OS will be defined as the time length between randomization and the date of death from any cause or the date of last follow-up in case of no documentation of death.
Measured: approx. 12 month

Secondary outcomes (2)

Progression-free survival (PFS)
PFS will be defined as the time length between the date of randomization and the date of first disease progression or death (whichever occurs first).
Measured: approx. 12 month
Quality of Life
Quality of life will be evaluated using the validated European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 questionnaire and the gastric module STO22.
Measured: approx. 12 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 20148 Oct 2020

First posted1 May 2014 (estimated)
Study startSep 2014
Primary completion8 Oct 2020
Study completion8 Oct 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Unresectable, Locally Advanced or Metastatic, Adenocarcinoma of the Stomach, or of the Gastro Esophageal JunctionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 242 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02128243
Sponsor's protocol ID: AIO-YMO-0111
Other IDs: 2013-002742-37
Acronym: MATEO
Status last verified: Mar 2021
First submitted: 29 Apr 2014
Last updated: 26 Mar 2021
Results posted: No
Data monitoring committee: No

Publications

Stocker G, Lorenzen S, Ettrich T, Herz AL, Longo F, Kiani A, Venerito M, Trojan J, Mahlberg R, Moosmann N, Chibaudel B, Kubicka S, Greil R, Daum S, Geissler M, Larcher-Senn J, Keller G, Lordick F, Haag GM. S-1 maintenance therapy in Caucasian patients with metastatic esophagogastric adenocarcinoma-final results of the randomized AIO MATEO phase II trial. ESMO Open. 2023 Jun;8(3):101572. doi: 10.1016/j.esmoop.2023.101572. Epub 2023 Jun 2.
PubMed 37270871
Haag GM, Stocker G, Quidde J, Jaeger D, Lordick F. Randomized controlled trial of S-1 maintenance therapy in metastatic esophagogastric cancer - the multinational MATEO study. BMC Cancer. 2017 Jul 31;17(1):509. doi: 10.1186/s12885-017-3497-9.
PubMed 28760152