Clinical trial NCT05384821: Metronomic Chemotherapy in Wilms Tumor (MetroWilms-1906)
Official title: Phase 1-2 Trial Evaluating Metronomic Chemotherapy in Patients With a Relapsed or Refractory Wilms Tumor
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Wilms Tumor
Keywords: Multidrug chemotherapy
metronomic chemotherapy
Wilms Tumor
Renal cancer
Lead sponsor: Centre Oscar Lambret
Sponsor class: OTHER
First posted: 2022-05-20
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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

Eligibility criteria: 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 outcomes:
measure: Disease control
timeFrame: 6 months after inclusion
Secondary outcomes:
measure: Progression-free survival
timeFrame: Up to progression, an average of 1 year
measure: Overall survival
timeFrame: Through study completion, an average of 12 months
measure: Tumor response
timeFrame: Immediately after each cycle of treatment, up to progression, an average of 1 year
measure: Adverse events
timeFrame: Through study completion, an average of 12 months (plus 30 days)
measure: The feasibility of evaluated therapy
timeFrame: Through study completion, an average of 12 months
measure: Quality of life of the patient (KindL)
timeFrame: Baseline, week 7 and week 13
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens Picardie
city: Besançon
country: France
facility: CHU de Besancon
city: Bordeaux
country: France
facility: CHRU de Bordeaux Hôpital des Enfants
city: Grenoble
country: France
facility: CHU GRENOBLE ALPES - Hôpital COUPLE ENFANT
city: Lille
country: France
facility: Centre Oscar Lambret
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Hôpital pour Enfants " La Timone " AP-HM
city: Montpellier
country: France
facility: CHU de MONTPELLIER - Hôpital Arnaud de Villeneuve
city: Nantes
country: France
facility: CHU Nantes
city: Nice
country: France
facility: CHU de Nice - Hôpital Archet 2
city: Paris
country: France
facility: Hôpital Armand-TROUSSEAU
city: Rennes
country: France
facility: CHU Hôpital Sud
city: Rouen
country: France
facility: Chu Rouen
city: Saint-Denis
country: France
facility: CHU La Réunion
city: Strasbourg
country: France
facility: CHRU Strasbourg - Hôpital de Hautepierre
city: Toulouse
country: France
facility: CHU Toulouse - Hôpital des Enfants
city: Vandœuvre-lès-Nancy
country: France
facility: CHRU NANCY - Hôpital d'Enfants
city: Villejuif
country: France
facility: Gustave ROUSSY
Study officials:
affiliation: Centre Oscar Lambret
name: Hélène SUDOUR-BONNANGE, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU La Timone
name: Arnauld VERSCHUUR, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: