Metronomic Chemotherapy in Wilms Tumor (MetroWilms-1906)

Centre Oscar Lambret

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Wilms Tumor

Treatments

Drug: Cis-Retinoic acid

Drug: Irinotecan

Drug: Temozolomide

Drug: Etoposide

Drug: Vincristine

Study type

Interventional

Funder types

Other

Identifiers

NCT05384821

MetroWilms-1906

Details and patient eligibility

About

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.

Full 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

Enrollment

28 estimated patients

Sex

All

Ages

18 months to 17 years old

Volunteers

No Healthy Volunteers

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)