Metronomic Chemotherapy in Wilms Tumor (MetroWilms-1906)

Wilms Tumor Clinical Trial

— MetroWilms  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05384821
• Other study ID #: MetroWilms-1906
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 14, 2022
• Est. completion date: October 2028

Study information

• Verified date: October 2023
• Source: Centre Oscar Lambret
• Contact: Emilie Heyman - Decoupigny
• Phone: +33 (0)3 20 29 59 18
• Email: promotion[@]o-lambret.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 28
• Est. completion date: October 2028
• Est. primary completion date: May 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Months to 17 Years

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 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)

Related Conditions & MeSH terms

• Wilms Tumor

Intervention

Drug:
• 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)

Locations

Country	Name	City	State
France	CHU Amiens Picardie	Amiens
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	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

Sponsors (1)

Lead Sponsor	Collaborator
Centre Oscar Lambret

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Overall survival	The time interval between study entry and death from any cause	Through study completion, an average of 12 months
Secondary	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
Secondary	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)
Secondary	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
Secondary	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