TEMOZOLOMIDE for Wilms tumor

Inclusion criteria

• {"criterion_text":"-Patient ≥18 months old and <18 years old"}
• {"criterion_text":"-Relapsed or refractory Wilms tumor, histologically proven at diagnosis"}
• {"criterion_text":"-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."}
• {"criterion_text":"-Radiologically measurable or evaluable disease (visible, target or nontarget- lesion on MRI or CT-scan)"}
• {"criterion_text":"-Performance status: Karnofsky performance status (for patients >16 years of age) or Lansky Play score (for patients ≤16 years of age) ≥ 70%."}
• {"criterion_text":"-Able to take oral medication or nasal gastric tube or authorized gastrostomy"}
• {"criterion_text":"-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)"}
• {"criterion_text":"-Creatinine ≤ 1,5 ULN or clearance ≥ 60 mL/ min/ 1,73m2 (In case of doubt, to be confirm by assessment of cystatin)"}
• {"criterion_text":"-Females of childbearing potential must have a negative seric pregnancy test within 7 days prior to initiation of treatment"}
• {"criterion_text":"-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."}
• {"criterion_text":"-Written informed consent from parents/legal representative, patient, and age-appropriate assent before any trial-specific screening procedures according to national guidelines."}
• {"criterion_text":"-Patient covered by the French \"Social Security\" regime"}

Exclusion criteria

• {"criterion_text":"-Prior history of other cancer within 5 years"}
• {"criterion_text":"-Target therapy within less than 5 * half-life of the substance prior to inclusion"}
• {"criterion_text":"-Major surgery within 15 days prior to inclusion"}
• {"criterion_text":"-Presence of any NCI-CTCAE v5 grade ≥ 2 cardiac, hepatic, pulmonary or renal toxicity"}
• {"criterion_text":"-Severe myelosuppression"}
• {"criterion_text":"-Severe peripheral neuropathy (grade ≥ 2)"}
• {"criterion_text":"-Fructose intolerance"}
• {"criterion_text":"-Inflammatory bowel chronic disease and/or intestinal obstruction"}
• {"criterion_text":"-Allergy to soy, peanuts"}
• {"criterion_text":"-Patients with demyelinating form of Charcot-Marie-Tooth disease"}
• {"criterion_text":"-Known active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection"}
• {"criterion_text":"-Known hypersensitivity to dacarbazine (DTIC), isotretinoin or to any of the trial drugs, trial drug classes, excipients in the formulation"}
• {"criterion_text":"-Hyperlipidemia and hypervitaminosis A"}
• {"criterion_text":"-Vaccination with a live attenuated vaccine within 1 month prior to inclusion"}
• {"criterion_text":"-Pregnant or breastfeeding patients"}
• {"criterion_text":"-Inability to comply with medical follow-up of the trial (geographical, social or psychological reasons)"}
• {"criterion_text":"-Chemotherapy or radiotherapy of target lesion within 3 weeks prior to inclusion"}

Primary endpoints

• {"endpoint_text":"-Dose limiting toxicity (DLT) over the first cycle (12 weeks, or more in case of temporary discontinuation).","definition_or_measurement_approach":"DLT assessed over the first cycle (12 weeks, or more in case of temporary discontinuation)."}
• {"endpoint_text":"- Disease control (complete response, partial response or stable disease) after 2 cycles of treatment, measured by the progression-free survival (PFS), approximately 6 months after inclusion.","definition_or_measurement_approach":"Disease control measured as complete response, partial response or stable disease after 2 cycles; assessed using progression-free survival (PFS) approximately 6 months after inclusion."}

Secondary endpoints

• {"endpoint_text":"-Progression free survival, computed as the time interval between trial entry and date of progression (according to central review, and using RECIST 1.1) or death from any cause. Patients still alive without evidence of disease progression at the time of their last visit will be censored at that date. We will use similar rules for censoring as for the primary endpoint.","definition_or_measurement_approach":"PFS computed from trial entry to progression (central review, RECIST 1.1) or death; censoring at last visit if no progression."}
• {"endpoint_text":"-Overall survival, computed as the time interval between trial entry and death from any cause. Patients still alive at the time of their last visit will be censored at that date.","definition_or_measurement_approach":"OS computed from trial entry to death from any cause; censoring at last visit if alive."}
• {"endpoint_text":"-Health-Related Quality of life (HRQoL) will be assessed using the age-appropriate Kindl® Quality of Life questionnaires (self- and proxy-assessment) (Ravens-Sieberer and Bullinger, 1998), with three time points (baseline and approximately at weeks 7 and 13).","definition_or_measurement_approach":"HRQoL assessed with age-appropriate Kindl® questionnaires (self and proxy) at baseline and ~weeks 7 and 13."}
• {"endpoint_text":"-Tumor response based on CT-scan or MRI imaging, using the same method over the whole trial period, and evaluated by central radiological review, using RECIST 1.1 criteria after each cycle of treatment (every 3 months approximately). The early response is based on the evaluation after one cycle. The best response is measured over the whole treatment duration.","definition_or_measurement_approach":"Tumor response assessed by CT or MRI, central radiological review using RECIST 1.1 after each cycle (~every 3 months); early response after one cycle; best response over treatment duration."}
• {"endpoint_text":"-Adverse events occurring from start of treatment until the end of trial treatment (plus 30 days) will be reported and graded using the NCI-CTCAE v5.0 classification, excluding those unequivocally related to the underlying disease or its progression.","definition_or_measurement_approach":"Adverse events collected from treatment start until end of treatment plus 30 days and graded per NCI-CTCAE v5.0; events clearly related to underlying disease/progression excluded."}
• {"endpoint_text":"-The feasibility of evaluated therapy will be assessed in terms of frequency of dose reductions or temporary stops of treatment, summarized by the relative dose intensity for each drug, and reasons for permanent discontinuation.","definition_or_measurement_approach":"Feasibility assessed by frequency of dose reductions/temporary stops, relative dose intensity per drug, and reasons for permanent discontinuation."}

France

Earliest CTIS Part Ii Submission Date

06-05-2024

Latest Decision Or Authorization Date

30-07-2025

Processing Time Days

450

Number Of Sites

16

Number Of Participants

28

Primary sponsor

Full Name

Centre Oscar Lambret

Organisation Type

Pharmaceutical company

Country Of Registered Address

France