Metronomic Chemotherapy in Wilms Tumor (MetroWilms-1906) (MetroWilms)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Wilms Tumor
• Intervention / Treatment: Drug: Vincristine; Drug: Irinotecan; Drug: Temozolomide; Drug: Etoposide; Drug: Cis-Retinoic acid

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

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Emilie Heyman - Decoupigny; Phone Number: +33 (0)3 20 29 59 18; Email: promotion@o-lambret.fr
• Study Contact Backup: Name: Marie Vanseymortier; Phone Number: +33 (0)3 20 29 59 18; Email: promotion@o-lambret.fr

Study Locations

• France
  • Amiens, France, 80054
    • Not yet recruiting
    • CHU Amiens Picardie
    • Contact: Leslie ANDRY, MD; Phone Number: +33 3 22 08 76 44; Email: andry.leslie@chu-amiens.fr
    • Principal Investigator: Leslie ANDRY, MD
  • Bordeaux, France, 33076
    • Recruiting
    • CHRU de Bordeaux Hôpital des Enfants
    • Contact: Anne NOTZ- CARRERE, MD; Phone Number: +33 5 57 82 04 34; Email: anne.notz-carrere@chu-bordeaux.fr
    • Principal Investigator: Anne NOTZ- CARRERE, MD
  • Grenoble, France, 38043
    • Recruiting
    • CHU Grenoble Alpes - Hopital Couple Enfant
    • Principal Investigator: Dominique PLANTAZ, MD
    • Contact: Dominique PLANTAZ, MD; Phone Number: +33 4 76 76 59 11; Email: DPlantaz@chu-grenoble.fr
  • Lille, France, 59020
    • Recruiting
    • Centre Oscar Lambret
    • Contact: Hélène SUDOUR-BONNANGE, MD; Phone Number: +33 3 20 29 59 56; Email: h-sudour@o-lambret.fr
    • Contact: Cyril LERVAT, MD; Phone Number: +33 3 20 29 59 56; Email: c-lervat@o-lambret.fr
    • Principal Investigator: Hélène SUDOUR-BONNANGE, MD
    • Principal Investigator: Cyril LERVAT, MD
  • Lyon, France, 69373
    • Recruiting
    • Centre Léon Bérard
    • Contact: Benoit DUMONT, MD; Phone Number: +33 4 69 16 65 74; Email: Benoit.DUMONT@ihope.fr
    • Principal Investigator: Benoit DUMONT, MD
  • Marseille, France, 13005
    • Recruiting
    • Hôpital pour Enfants " La Timone " AP-HM
    • Contact: Arnauld VERSCHUUR, MD; Phone Number: +33 4 91 38 86 21; Email: arnauld.verschuur@ap-hm.fr
    • Principal Investigator: Arnauld Verschuur, MD
  • Montpellier, France, 34295
    • Not yet recruiting
    • CHU de Montpellier - Hôpital Arnaud de Villeneuve
    • Contact: Stéphanie HAOUY, MD; Phone Number: +33 4 67 33 65 19; Email: s-haouy@chu-montpellier.fr
    • Principal Investigator: Stéphanie HAOUY, MD
  • Nantes, France, 44093
    • Recruiting
    • CHU Nantes
    • Contact: Estelle THEBAUD, MD; Phone Number: +33 2 40 08 36 10; Email: Estelle.THEBAUD@chu-nantes.fr
    • Principal Investigator: Estelle THEBAUD, MD
  • Nice, France, 06202
    • Recruiting
    • CHU de NICE - Hôpital Archet 2
    • Contact: Joy BENADIBA, MD; Phone Number: +33 4 92 03 92 68; Email: benadiba.j@chu-nice.fr
    • Principal Investigator: Joy BENADIBA, MD
  • Paris, France, 75012
    • Recruiting
    • Hôpital Armand-Trousseau
    • Contact: Marie Dominique TABONE, MD; Phone Number: +33 1 44 73 68 46; Email: marie-dominique.tabone@aphp.fr
    • Principal Investigator: Marie Dominique TABONE, MD
  • Rennes, France, 35203
    • Recruiting
    • CHU Hôpital Sud
    • Contact: Jacinthe BONNEAU-LAGACHERIE, MD; Phone Number: +33 2 99 26 59 17; Email: Jacinthe.BONNEAU-LAGACHERIE@chu-rennes.fr
    • Principal Investigator: Jacinthe BONNEAU-LAGACHERIE, MD
  • Rouen, France, 76000
    • Recruiting
    • CHU Rouen
    • Contact: Aude MARIE-CARDINE, MD; Phone Number: +33 2 32 88 81 91; Email: Aude.Marie-Cardine@chu-rouen.fr
    • Principal Investigator: Aude MARIE-CARDINE, MD
  • Strasbourg, France, 67098
    • Recruiting
    • CHRU Strasbourg - Hôpital de Hautepierre
    • Principal Investigator: Sarah JANNIER, MD
    • Contact: Sarah JANNIER, MD; Phone Number: +33 3 88 12 87 94; Email: sarah.jannier@chru-strasbourg.fr
  • Toulouse, France, 70034
    • Not yet recruiting
    • CHU Toulouse - Hôpital des Enfants
    • Principal Investigator: Cécile BOULANGER, MD
    • Contact: Cécile BOULANGER, MD; Phone Number: +33 5 34 55 75 66; Email: boulanger.c@chu-toulouse.fr
  • Vandœuvre-lès-Nancy, France, 54500
    • Recruiting
    • CHRU NANCY - Hôpital d'Enfants
    • Principal Investigator: Ludovic MANSUY, MD
    • Contact: Ludovic MANSUY, MD; Phone Number: +33 3 83 15 47 34; Email: lu.mansuy@chru-nancy.fr
  • Villejuif, France, 94805
    • Recruiting
    • Gustave Roussy
    • Contact: Claudia PASQUALINI, MD; Phone Number: +33 1 42 11 42 11; Email: Claudia.pasqualini@gustaveroussy.fr
    • Principal Investigator: Claudia PASQUALINI, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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 study 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 study drug and for 6 months after stopping the study drug for both female and male patients.
• Written informed consent from parents/legal representative, patient, and age-appropriate assent before any study-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 study drugs, study 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Single Arm - Vincristine + Irinotécan + Témozolomide + Etoposide + Cis-Retinoic acid; Metronomic chemotherapy : Vincristine + Irinotécan + Témozolomide + Etoposide + Cis-Retinoic acid

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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control	Complete response, partial response or stable disease after 2 cycles of treatment, measured by the progression-free survival (PFS).	6 months after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	The time interval between study entry and date of progression (using RECIST 1.1)	Up to progression, an average of 1 year
Overall survival	The time interval between study entry and death from any cause	Through study completion, an average of 12 months
Tumor response	Using CT-scan or MRI imaging (using RECIST 1.1)	Immediately after each cycle of treatment, up to progression, an average of 1 year
Adverse events	The adverse events (AE) are collected to evaluate the safety of the study treatment.	Through study completion, an average of 12 months (plus 30 days)
The feasibility of evaluated therapy	assessed in terms of frequency of dose reductions or temporary stops of treatment	Through study completion, an average of 12 months
Quality of life of the patient (KindL)	Ravens-Sieberer and Bullinger Quality of Life Questionnaire will be used to measure the quality of life of the patients. The score can go from 0 to 100, and the higher score corresponds to a higher health-related quality of life	Baseline, week 7 and week 13

Collaborators and Investigators

• Sponsor: Centre Oscar Lambret
• Investigators: Principal Investigator: Hélène SUDOUR-BONNANGE, MD, Centre Oscar Lambret; Principal Investigator: Arnauld VERSCHUUR, MD, PhD, CHU La Timone

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2022
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: November 8, 2021
• First Submitted That Met QC Criteria: May 18, 2022
• First Posted (Actual): May 20, 2022

Study Record Updates

• Last Update Posted (Actual): October 16, 2023
• Last Update Submitted That Met QC Criteria: October 13, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Renal cancer; metronomic chemotherapy; Wilms Tumor; Multidrug chemotherapy
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Genetic Diseases, Inborn; Kidney Neoplasms; Neoplastic Syndromes, Hereditary; Neoplasms, Complex and Mixed; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Wilms Tumor; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Keratolytic Agents; Topoisomerase I Inhibitors; Etoposide; Temozolomide; Irinotecan; Vincristine; Tretinoin; Isotretinoin
• Other Study ID Numbers: MetroWilms-1906

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No