Trial of S-1 Maintenance Therapy in Metastatic Esophagogastric Cancer

NCT02128243 | Completed Phase 2

• 2 other identifiers: AIO-YMO-01112013-002742-37
• Study Type: interventional
• Target: 242
• Locations: 1 country
• Sites: 1

Brief 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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  approx. 12 month

Secondary Outcomes (2)

• Progression-free survival (PFS)

  approx. 12 month

• Quality of Life

  approx. 12 month

Other Outcomes (3)

• Malnutrition

  approx. 12 month

• Overall Survival of non-randomized patients

  approx. 12 month

• Adverse Events

  approx. 12 month

Study Arms (2)

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.

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.

Drug: Chemotherapy by Investigator's choice

Interventions

S-1 de-escalation DRUG

S-1 30 mg/m² bid d1-14 q21d

Also known as: Teysuno

Arm A: De-escalation therapy

Chemotherapy by Investigator's choice DRUG

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

Also known as: FLO regimen, - Oxaliplatin 85 mg/m², - Leucovorin 200 mg/m², - 5-Fluorouracil 2600 mg/m², mod. FOLFOX-6 regimen, - Leucovorin 400 mg/m², - 5-Fluorouracil 400 mg/m², - 5-Fluorouracil 2400 mg/m², Cisplatin / S-1, - Cisplatin 75 mg/m², - S-1 25mg/m², EOX/EOF, - Epirubicin 50 mg/m², - Oxaliplatin 130 mg/m², - Capecitabine 625 mg/m², FLOT, - Docetaxel 50 mg/m², - Leucovorin 200 mg/mg², Cisplatin, 5-FU, - Cisplatin 75 (-100) mg/m², - 5-FU 800 (-1000) mg/m², Cisplatin / Capecitabine (XP), - Cisplatin 80 mg/m², - Capecitabine 1000 mg/m²

Arm B: Chemotherapy by Investigator's choice

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• AIO-Studien-gGmbH: lead
• Taiho Pharmaceutical Co., Ltd.: collaborator
• Nordic Pharma SAS: collaborator

Study Sites (1)

NCT-Med. Onkologie

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Related Publications (2)

• 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.

  PMID: 37270871 DERIVED

• 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.

  PMID: 28760152 DERIVED

Related Links

• Working Group for Medical Oncology (AIO) from the German Cancer Society (DKG)

MeSH Terms

Conditions

Neoplasm Metastasis; Stomach Neoplasms; Adenocarcinoma Of Esophagus; Esophageal Neoplasms

Interventions

tegafur-gimeracil-oteracil; Oxaliplatin; Leucovorin; Fluorouracil; Cisplatin; S 1 (combination); Epirubicin; Capecitabine; Docetaxel

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Study Officials

• Georg Martin Haag, Dr.

  NCT-Med. Onkologie

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2014
• First Posted: May 1, 2014
• Study Start: September 1, 2014
• Primary Completion: October 8, 2020
• Study Completion: October 8, 2020
• Last Updated: March 26, 2021

Record last verified: 2021-03

Locations

DE (1)