Recruiting
Phase 1/2
Metronomic Chemotherapy in Wilms Tumor (MetroWilms-1906)
Condition(s) studied
Wilms Tumor
Investigational drug(s) / intervention(s)
Vincristine: IV, D1-D22-D43 and D64
Irinotecan: Oral, 5 days/week during W1,W2,W7 and W8 (D1 to D5, D8 to D12, D43 to D47, D50 to D54)
Temozolomide: Oral,3 weeks in a row, twice per cycle (D1 to D21, D43 to D63)
Etoposide: Oral, 3 weeks in a row, twice per cycle (D22 to D42, D64 to D84)
Cis-Retinoic acid: Oral, 2 weeks in a row, thrice per cycle (D15 to D28, D43 to D56, D71 to D84)
Study summary
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.
Eligibility
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)
Primary outcome measure(s)
- Disease control — 6 months after inclusion
Complete response, partial response or stable disease after 2 cycles of treatment, measured by the progression-free survival (PFS).
Trial sites (18)
| Facility | City | Region | Status |
| CHU Amiens Picardie |
Amiens |
France |
Not Yet Recruiting |
| CHU de Besancon |
Besançon |
France |
Recruiting |
| CHRU de Bordeaux Hôpital des Enfants |
Bordeaux |
France |
Recruiting |
| CHU GRENOBLE ALPES - Hôpital COUPLE ENFANT |
Grenoble |
France |
Recruiting |
| Centre Oscar Lambret |
Lille |
France |
Recruiting |
| Centre Léon Bérard |
Lyon |
France |
Recruiting |
| Hôpital pour Enfants " La Timone " AP-HM |
Marseille |
France |
Recruiting |
| CHU de MONTPELLIER - Hôpital Arnaud de Villeneuve |
Montpellier |
France |
Not Yet Recruiting |
| CHU Nantes |
Nantes |
France |
Recruiting |
| CHU de Nice - Hôpital Archet 2 |
Nice |
France |
Recruiting |
| Hôpital Armand-TROUSSEAU |
Paris |
France |
Recruiting |
| CHU Hôpital Sud |
Rennes |
France |
Recruiting |
| Chu Rouen |
Rouen |
France |
Recruiting |
| CHU La Réunion |
Saint-Denis |
France |
Not Yet Recruiting |
| CHRU Strasbourg - Hôpital de Hautepierre |
Strasbourg |
France |
Recruiting |
| CHU Toulouse - Hôpital des Enfants |
Toulouse |
France |
Recruiting |
| CHRU NANCY - Hôpital d'Enfants |
Vandœuvre-lès-Nancy |
France |
Recruiting |
| Gustave ROUSSY |
Villejuif |
France |
Recruiting |
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