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RECRUITINGPhase 1 / Phase 2INTERVENTIONAL

Metronomic Chemotherapy in Wilms Tumor (MetroWilms-1906)

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

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: - 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 willing to sign a consent form 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 Who Should NOT Join This Trial: - Prior history of other cancer within 5 years - Chemotherapy or radiotherapy of target lesion within 3 weeks prior to inclusion ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: * 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 Exclusion Criteria: * 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)

Treatments Being Tested

DRUG

Vincristine

IV, D1-D22-D43 and D64

DRUG

Irinotecan

Oral, 5 days/week during W1,W2,W7 and W8 (D1 to D5, D8 to D12, D43 to D47, D50 to D54)

DRUG

Temozolomide

Oral,3 weeks in a row, twice per cycle (D1 to D21, D43 to D63)

DRUG

Etoposide

Oral, 3 weeks in a row, twice per cycle (D22 to D42, D64 to D84)

DRUG

Cis-Retinoic acid

Oral, 2 weeks in a row, thrice per cycle (D15 to D28, D43 to D56, D71 to D84)

Locations (18)

CHU Amiens Picardie
Amiens, France
CHU de Besancon
Besançon, France
CHRU de Bordeaux Hôpital des Enfants
Bordeaux, France
CHU GRENOBLE ALPES - Hôpital COUPLE ENFANT
Grenoble, France
Centre Oscar Lambret
Lille, France
Centre Léon Bérard
Lyon, France
Hôpital pour Enfants " La Timone " AP-HM
Marseille, France
CHU de MONTPELLIER - Hôpital Arnaud de Villeneuve
Montpellier, France
CHU Nantes
Nantes, France
CHU de Nice - Hôpital Archet 2
Nice, France
Hôpital Armand-TROUSSEAU
Paris, France
CHU Hôpital Sud
Rennes, France
Chu Rouen
Rouen, France
CHU La Réunion
Saint-Denis, France
CHRU Strasbourg - Hôpital de Hautepierre
Strasbourg, France
CHU Toulouse - Hôpital des Enfants
Toulouse, France
CHRU NANCY - Hôpital d'Enfants
Vandœuvre-lès-Nancy, France
Gustave ROUSSY
Villejuif, France