Etude : GERICO14 /



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Acronyme / Nom
Situation thérapeutique
Traitement
Cadre réglementaire
MÀJ
Présentation de l'étude
Acronyme / Nom : GERICO14

Situation thérapeutique : Métastatique ou localement avancé

Traitement : Chimiothérapie

Cadre réglementaire : RIPH1

Dernière MÀJ : 29/11/2021
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : Etude de phase III randomisée cyclophosphamide oral vs doxorubicine en 1ère ligne de chimiothérapie chez les patients âgés ≥ 65 ans atteints de sarcome des tissus mous métastatique ou avancé : Essai multicentrique du groupe GERICO/UNICANCER

Spécialité : Tissu mésothélial et tissus mous
Localisation : C49 - Tumeur maligne du tissu conjonctif et des autres tissus mous

Spécialité : Tissu mésothélial et tissus mous
Localisation : C48 - Tumeur maligne du rétropéritoine et du péritoine

Spécialité : Tissu mésothélial et tissus mous
Localisation : C49 - Tumeur maligne du tissu conjonctif et des autres tissus mous

Spécialité : Tissu mésothélial et tissus mous
Localisation : C.5 - Tissu mésothélial et tissus mous : autres et non précisés
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : STUDY DESIGN:
Co-morbidities increase in number and severity with age, competing with cancer prognosis and making prioritizing medical issues necessary. Individualization of cancer treatment by integrating a comprehensive geriatric assessment (CGA) is frequently considered as essential and mandatory for elderly cancer patients. The G8 questionnaire is able to identify patients requiring CGA, with a threshold score of ≤14/17 and with a strong 1-year prognostic value.

According to guidelines, the recommended first-line treatment of these patients relies on single agent chemotherapy with anthracyclines (including doxorubicin); however, anthracycline-based treatments have modest performance in patients with metastatic STS with a median progression-free survival of about 4 months and an overall survival of about 12 months.

Previous studies have demonstrated promising activity of oral metronomic cyclophosphamide in STS patients and its favorable safety profile.

To evaluate this promising activity we designed a phase III, randomized, open-label, multicentric study comparing daily oral cyclophosphamide versus standard 3-week intravenous injection of doxorubicin in 65 years or older patients with advanced or metastatic STS.


STUDY ARMS:
- Active Comparator: Doxorubicin
Intravenous Doxorubicin 60 mg/m² Cycle 1 then 75 mg/m² Cycle 2 to Cycle 6 D1-D21 with granulocyte-colony stimulating factor (G-CSF) and dexrazoxane.

- Experimental: Cyclophosphamide
Cyclophosphamide per os 100 mg twice a day, 1 week on, 1 week off until 2 years, or unacceptable toxicity, disease progression, withdrawn of consent or death.


MAIN OBJECTIVE:
The primary objective is to investigate whether treatment with oral cyclophosphamide improves the outcome of elderly patients (≥65 years old) with
advanced/metastatic STS, compared with doxorubicin in term of PFS.

SECONDARY OBJECTIVES:
- Comparison of oral cyclophosphamide versus doxorubicin in terms of additional efficacy endpoints:
- Overall survival (OS);
- Best response under treatment;
- Time until definitive deterioration (TUDD) of health-related quality of life (HRQoL);
- Assessment of the toxicity profile of oral cyclophosphamide and doxorubicin, as per NCI CTCAE v5.0.
- Assessment of the prognostic value on efficacy (PFS, OS)
- Assessment of the geriatric characteristics of the randomized population,
- Assessment of compliance to oral metronomic cyclophosphamide (arm B only)

Phase : III

Stade : Localement avancé à Métastatique

1
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : 1. Patient must have signed a written informed consent form prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trust person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient’s consent
2. Age ≥65 years (inclusions will be managed to ensure that at least 50% of the randomized patients are ≥75 years old)
3. Diagnosis of soft-tissue sarcoma histologically confirmed by RRePS (Réseau de Référence en Pathologie des Sarcomes et des Viscères)
4. Metastatic or locally advanced disease not amenable to surgery, radiation, or combined modality treatment with curative intent. Palliative radiation therapy is permitted only if direct on nontarget lesion
5. Documentation of disease progression within the last 6 months before randomization
6. Measurable disease, defined as at least 1 unidimensionally measurable lesion on a CT-scan as defined by response evaluation criteria in solid tumors (RECIST) v1.1
7. Life expectancy of at least 6 months
8. Eastern Cooperative Oncology Group (ECOG) performance status ≤2
9. G8 score >14
10. Left ventricular ejection fraction (LVEF) value by echocardiogram or Multiple gated acquisition scanning (MUGA) ≥55%
11. Adequate bone marrow, renal, and hepatic function, as evidenced by the following within 7 days of study treatment initiation:
a. Absolute neutrophil count (ANC) ≥1,000/mm3
b. Platelets ≥100,000/mm3
c. Hemoglobin ≥9.0 g/dL
d. Serum creatinine ≤2 x upper limit of normal (ULN)
e. Glomerular filtration rate (GFR) ≥50 ml/min/1.73m2 (calculated with MDRD)
f. AST and ALT ≤2.5 x ULN (≤5.0 × ULN for patients with liver involvement of their cancer )
g. Total bilirubin ≤1.5 X ULN
h. Alkaline phosphatase ≤2.5 x ULN (≤5 x ULN with liver involvement of their cancer)
i. serum albumin > 25 g/L
j. Prothrombin time (PT)/International normalized ratio (INR) ≤1.5 x ULN
Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists. Close monitoring of at least weekly evaluations will be performed until PT/INR is stable based on a measurement that is pre-dose as defined by the local standard of care.
12. Male patients must agree to use adequate contraception for the duration of trial participation and up to 6 months after completing treatment/therapy. Adequate contraception is defined as any medically recommended method (or combination of methods) as per standard of care
13. Patients must be affiliated to a Social Security System (or equivalent)
14. Patient is willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures including follow-up

Critères de non-inclusion : 1. Previous systemic treatment for advance or metastatic sarcoma
2. Previous neoadjuvant or adjuvant anthracycline treatment for localized sarcoma
3. Soft-tissue sarcoma with the following histological subtypes: dermatofibrosarcoma protuberans, desmoid tumor, alveolar or embryonal rhabdomyosarcoma, Desmoplastic small round cell tumor, Kaposi Sarcoma, Gastro-Intestinal stromal tumor, Peripheral neuroectodermal tumors
4. Primary bone sarcoma (including osteosarcoma, Ewing tumor, chondrosarcoma, and chordoma)
5. Symptomatic or known central nervous system (CNS) metastases
6. Known history of or concomitant malignancy likely to affect life expectancy in the judgment of the investigator and history of radiotherapy mediastinal in the last five years
7. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before Day 1 of treatment
8. Active cardio vascular disease including any of the following: Congestive heart failure (New York Heart Association [NYHA] ≥Class 2), unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months), acute inflammatory cardiopathy, severe arythmia, high risk of bleeding, cerebrovascular accident within the last 6 months
9. Uncontrolled grade >2 hypertension. (Systolic blood pressure ≥160 mmHg or diastolic pressure ≥100 mmHg despite optimal medical management)
10. Ongoing infection ≥Grade 2 according to NCI Common Terminology Criteria for Adverse Events version (CTCAE v. 5.0)
11. Known history of human immunodeficiency virus (HIV) infection
12. Known history of chronic hepatitis B or C
13. History of organ allograft
14. Pre-existing acute hemorrhagic cystitis, urinary tract obstruction, acute urinary tract infection
15. Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study
16. Substance abuse, medical condition, that may interfere with the patient's participation in the study or evaluation of the study results
17. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation
18. Inability to swallow oral medications, any malabsorption condition.
19. Persons deprived of their liberty or under protective custody or guardianship
20. Participation in another therapeutic trial within the 30 days prior to randomization and during the study
21. Patients having received live attenuated vaccine therapy used for prevention of diseases as influenza, chickenpox, zoster, measles, mumps, rubella, tuberculosis, rotavirus or yellow fever within 4 weeks of the first dose of study drug. These vaccinations are not permitted during the study up to 6 months after the last treatment
22. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT04757337
Promoteur :
Unicancer
Type de sponsor : Institutionnel
3, avenue du Général Harris
14000 CAEN

Coordonnateur :
docteur Thibaud VALENTIN
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Oscar Lambret - 3 Rue Frédéric Combemale - 59000 LILLE

Investigateur :
Docteur Thomas RYCKEWAERT

TEC / ARC / IDE :
Unité Intégrée de Recherche Clinique
investigation@
o-lambret.fr
03.20.29.59.35

Statut de l'essai : OUVERT

MAJ : 28/06/2021