Wilms Tumor
Conditions
Keywords
Multidrug chemotherapy, metronomic chemotherapy, Wilms Tumor, Renal cancer
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
Interventions
DRUGVincristine
IV, D1-D22-D43 and D64
DRUGIrinotecan
Oral, 5 days/week during W1,W2,W7 and W8 (D1 to D5, D8 to D12, D43 to D47, D50 to D54)
DRUGTemozolomide
Oral,3 weeks in a row, twice per cycle (D1 to D21, D43 to D63)
DRUGEtoposide
Oral, 3 weeks in a row, twice per cycle (D22 to D42, D64 to D84)
Oral, 2 weeks in a row, thrice per cycle (D15 to D28, D43 to D56, D71 to D84)
Sponsors
Centre Oscar Lambret
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Months to 17 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
France
Contacts
CONTACTEmilie Heyman - Decoupigny
CONTACTMarie Vanseymortier
PRINCIPAL_INVESTIGATORHélène SUDOUR-BONNANGE, MD
Centre Oscar Lambret
PRINCIPAL_INVESTIGATORArnauld VERSCHUUR, MD, PhD
CHU La Timone
Outcome results
None listed