Metronomic Chemotherapy in Wilms Tumor (MetroWilms-1906)

Sponsor

Centre Oscar Lambret (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05384821

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

2.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Wilms Tumor	Drug: Vincristine Drug: Irinotecan Drug: Temozolomide Drug: Etoposide Drug: Cis-Retinoic acid	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

28 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

May 1, 2022

Anticipated Primary Completion Date :

Jan 1, 2027

Anticipated Study Completion Date :

Jan 1, 2028

Arms and Interventions

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)

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)

Outcome Measures

Primary Outcome Measures

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).

Secondary Outcome Measures

Progression-free survival [Up to progression, an average of 1 year]
The time interval between study entry and date of progression (using RECIST 1.1)
Overall survival [Through study completion, an average of 12 months]
The time interval between study entry and death from any cause
Tumor response [Immediately after each cycle of treatment, up to progression, an average of 1 year]
Using CT-scan or MRI imaging (using RECIST 1.1)
Adverse events [Through study completion, an average of 12 months (plus 30 days)]
The adverse events (AE) are collected to evaluate the safety of the study treatment.
The feasibility of evaluated therapy [Through study completion, an average of 12 months]
assessed in terms of frequency of dose reductions or temporary stops of treatment
Quality of life of the patient (KindL) [Baseline, week 7 and week 13]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Months to 35 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient ≥18 months old and ≤ 35 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)

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CHU Amiens Picardie	Amiens	France	80054
2	CHRU de Bordeaux Hôpital des Enfants	Bordeaux	France	33076
3	CHU GRENOBLE ALPES - Hôpital COUPLE ENFANT	Grenoble	France	38043
4	Centre Oscar Lambret	Lille	France	59020
5	Hôpital pour Enfants " La Timone " AP-HM	Marseille	France	13005
6	CHU de Nice - Hôpital Archet 2	Nice	France	06202
7	Hôpital Armand-TROUSSEAU	Paris	France	75012
8	CHU Hôpital Sud	Rennes	France	35203
9	Chu Rouen	Rouen	France	76000
10	CHRU Strasbourg - Hôpital de Hautepierre	Strasbourg	France	67098
11	CHU Toulouse - Hôpital des Enfants	Toulouse	France	70034
12	CHRU NANCY - Hôpital d'Enfants	Vandœuvre-lès-Nancy	France	54500