Phase 1-2 Trial Evaluating Metronomic Chemotherapy in Patients With a Relapsed or Refractory Wilms Tumor
Overview
- Phase
- Phase 1
- Intervention
- Vincristine
- Conditions
- Wilms Tumor
- Sponsor
- Centre Oscar Lambret
- Enrollment
- 28
- Locations
- 18
- Primary Endpoint
- Disease control
- Status
- Recruiting
- Last Updated
- last month
Overview
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
Investigators
Eligibility Criteria
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 )
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
Arms & Interventions
Single Arm - Vincristine + Irinotécan + Témozolomide + Etoposide + Cis-Retinoic acid
Metronomic chemotherapy : Vincristine + Irinotécan + Témozolomide + Etoposide + Cis-Retinoic acid
Intervention: Vincristine
Single Arm - Vincristine + Irinotécan + Témozolomide + Etoposide + Cis-Retinoic acid
Metronomic chemotherapy : Vincristine + Irinotécan + Témozolomide + Etoposide + Cis-Retinoic acid
Intervention: Irinotecan
Single Arm - Vincristine + Irinotécan + Témozolomide + Etoposide + Cis-Retinoic acid
Metronomic chemotherapy : Vincristine + Irinotécan + Témozolomide + Etoposide + Cis-Retinoic acid
Intervention: Temozolomide
Single Arm - Vincristine + Irinotécan + Témozolomide + Etoposide + Cis-Retinoic acid
Metronomic chemotherapy : Vincristine + Irinotécan + Témozolomide + Etoposide + Cis-Retinoic acid
Intervention: Etoposide
Single Arm - Vincristine + Irinotécan + Témozolomide + Etoposide + Cis-Retinoic acid
Metronomic chemotherapy : Vincristine + Irinotécan + Témozolomide + Etoposide + Cis-Retinoic acid
Intervention: Cis-Retinoic acid
Outcomes
Primary Outcomes
Disease control
Time Frame: 6 months after inclusion
Complete response, partial response or stable disease after 2 cycles of treatment, measured by the progression-free survival (PFS).
Secondary Outcomes
- Overall survival(Through study completion, an average of 12 months)
- Tumor response(Immediately after each cycle of treatment, up to progression, an average of 1 year)
- The feasibility of evaluated therapy(Through study completion, an average of 12 months)
- Progression-free survival(Up to progression, an average of 1 year)
- Adverse events(Through study completion, an average of 12 months (plus 30 days))
- Quality of life of the patient (KindL)(Baseline, week 7 and week 13)