Metronomic Chemotherapy in Wilms Tumor (MetroWilms-1906)

Официальное название

Phase 1-2 Trial Evaluating Metronomic Chemotherapy in Patients With a Relapsed or Refractory Wilms Tumor

Обзор

This is a multicenter, interventional, non-randomized study among patients with a relapsed or refractory Wilms tumor. The study will aim to assess efficacy of metronomic chemotherapy, in terms of disease control after two cycles of metronomic chemotherapy.

Подробное описание

The main aim of this study is to assess efficacy of metronomic chemotherapy, in terms of disease control after two cycles of metronomic chemotherapy .

Other objectives of the study include:

* To evaluate disease control obtained with metronomic chemotherapy, in terms of progression-free survival (PFS) and overall survival (OS). * Evaluating early response after one cycle of treatment of metronomic treatment; * Evaluating best tumor response over the whole metronomic treatment duration; * Evaluating safety of the proposed metronomic chemotherapy; * Evaluating the feasibility of the proposed metronomic chemotherapy. * To evaluate quality of life using Kindl® Quality of Life questionnaire at baseline (before start of treatment), and approximately at weeks 7 and 13 of treatment

Вмешательства

• Препарат Vincristine
  IV, D1-D22-D43 and D64
• Препарат Irinotecan
  Oral, 5 days/week during W1,W2,W7 and W8 (D1 to D5, D8 to D12, D43 to D47, D50 to D54)
• Препарат Temozolomide
  Oral,3 weeks in a row, twice per cycle (D1 to D21, D43 to D63)
• Препарат Etoposide
  Oral, 3 weeks in a row, twice per cycle (D22 to D42, D64 to D84)
• Препарат Cis-Retinoic acid
  Oral, 2 weeks in a row, thrice per cycle (D15 to D28, D43 to D56, D71 to D84)

Первичные конечные точки

• Disease control [Срок оценки: 6 months after inclusion]

Вторичные конечные точки (6)

• Progression-free survival [Срок оценки: Up to progression, an average of 1 year]
• Overall survival [Срок оценки: Through study completion, an average of 12 months]
• Tumor response [Срок оценки: Immediately after each cycle of treatment, up to progression, an average of 1 year]
• Adverse events [Срок оценки: Through study completion, an average of 12 months (plus 30 days)]
• The feasibility of evaluated therapy [Срок оценки: Through study completion, an average of 12 months]
• Quality of life of the patient (KindL) [Срок оценки: Baseline, week 7 and week 13]

Критерии участия

Критерии включения

• Patient ≥18 months old and ≤ 17 years old
• Relapsed or refractory Wilms tumor, histologically proven at diagnosis
• After at least 2 lines of chemotherapy (conventional or high dose, which may include the trial molecules) or after 1 line for high risk relapse for which there would not be any curative therapy. If 1 line for high risk relapse, the enrolment should be confirmed by coordinators.
• Radiologically measurable or evaluable disease (visible, target or non-target-lesion on MRI or CT-scan)
• Performance status: Karnofsky performance status (for patients >16 years of age) or Lansky Play score (for patients ≤16 years of age) ≥ 70%.
• Able to take oral medication or nasal gastric tube or authorized gastrostomy
• Adequate biological criteria:

• Neutrophils > 1000/mm3 ; Platelets > 75 000/mm3
• Transaminases (ALT/ AST) ≤ 3 times ULN (or ≤ 6 times ULN if liver metastasis); total bilirubin ≤ 2 ULN (except in case of Gilbert's disease)
• Creatinine ≤ 1,5 ULN or clearance ≥ 60 mL/ min/ 1,73m2 (In case of doubt, to be confirm by assessment of cystatin )
• Females of childbearing potential must have a negative seric pregnancy test within 7 days prior to initiation of treatment.
• Sexually active patients must agree to use adequate and appropriate contraception (at least one highly effective contraception or two complementary methods of contraception), 1 month before beginning of treatment while on trial drug and for 7 months after stopping the trial drug for female patients and after 6 months for male patients.
• Written informed consent from parents/legal representative, patient, and age-appropriate assent before any trial-specific screening procedures according to national guidelines.
• Patient covered by the French "Social Security" regime

Критерии исключения

• Prior history of other cancer within 5 years
• Chemotherapy or radiotherapy of target lesion within 3 weeks prior to inclusion
• Target therapy within less than 5 \* half-life of the substance prior to inclusion
• Major surgery within 15 days prior to inclusion
• Presence of any NCI-CTCAE v5 grade ≥ 2 cardiac, hepatic, pulmonary or renal toxicity
• Severe myelosuppression
• Severe peripheral neuropathy (grade ≥ 2)
• Fructose intolerance
• Inflammatory bowel chronic disease and/or intestinal obstruction
• Patients with demyelinating form of Charcot-Marie-Tooth disease
• Known active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection.
• Known hypersensitivity to dacarbazine (DTIC), isotretinoin or to any of the trial drugs, trial drug classes, excipients in the formulation
• Hyperlipidemia and hypervitaminosis A
• Vaccination with a live attenuated vaccine within 1 month prior to inclusion
• Pregnant or breastfeeding patients
• Inability to comply with medical follow-up of the trial (geographical, social or psychological reasons)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 18 центров

• CHU Amiens Picardie — Amiens
• CHU de Besancon — Besançon
• CHRU de Bordeaux Hôpital des Enfants — Bordeaux
• CHU GRENOBLE ALPES - Hôpital COUPLE ENFANT — Grenoble
• Centre Oscar Lambret — Lille
• Centre Léon Bérard — Lyon
• Hôpital pour Enfants " La Timone " AP-HM — Marseille
• CHU de MONTPELLIER - Hôpital Arnaud de Villeneuve — Montpellier
• … и ещё 10 центров

Идентификаторы

NCT: NCT05384821 · MetroWilms-1906 · PHRC-K22-018 · 2022-502687-20-00 · 2021-002540-67

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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