MetroWilms

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Oscar Lambret

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

14 Sep 2022 → ongoing

Decision date (initial)

2024-05-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2022-502687-20-00

EudraCT number

2021-002540-67

ClinicalTrials.gov

NCT05384821

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

First stage: Evaluate the safety and the feasibility of the metronomic chemotherapy regimen (Vincristine/Irinotecan/Etoposide/Temozolomide/ Cis-Retinoic acid in children and teenagers with a relapsed or refractory Wilms tumor.
2nd stage: To evaluate efficacy of metronomic chemotherapy in patients with a relapsed or refractory Wilms tumor, in terms of disease control after two cycles of metronomic chemotherapy (approximately 6 months).

Secondary objectives 6

1. To evaluate disease control obtained with metronomic chemotherapy, in terms of progression-free survival (PFS) and overall survival (OS).
2. To evaluate quality of life using kidKindl® Quality of Life questionnaire at baseline (before start of treatment), and approximately at weeks 7 and 13 of treatment.
3. To evaluate early response after one cycle of treatment of metronomic treatment.
4. To evaluate best tumor response over the whole metronomic treatment duration.
5. To evaluate safety of the proposed metronomic chemotherapy.
6. To evaluate the feasibility of the proposed metronomic chemotherapy.

Conditions and MedDRA coding

Wilms tumor

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Patient ≥18 months old and <18 years old
2. Relapsed or refractory Wilms tumor, histologically proven at diagnosis
3. 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.
4. Radiologically measurable or evaluable disease (visible, target or nontarget- lesion on MRI or CT-scan)
5. Performance status: Karnofsky performance status (for patients >16 years of age) or Lansky Play score (for patients ≤16 years of age) ≥ 70%.
6. Able to take oral medication or nasal gastric tube or authorized gastrostomy
7. 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)
8. Creatinine ≤ 1,5 ULN or clearance ≥ 60 mL/ min/ 1,73m2 (In case of doubt, to be confirm by assessment of cystatin)
9. Females of childbearing potential must have a negative seric pregnancy test within 7 days prior to initiation of treatment
10. 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.
11. Written informed consent from parents/legal representative, patient, and age-appropriate assent before any trial-specific screening procedures according to national guidelines.
12. Patient covered by the French "Social Security" regime

Exclusion criteria 17

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. -Dose limiting toxicity (DLT) over the first cycle (12 weeks, or more in case of temporary discontinuation). - 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.

Secondary endpoints 6

1. 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.
2. 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.
3. 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).
4. 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.
5. 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.
6. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Oscar Lambret

Sponsor organisation

Centre Oscar Lambret

Address

3 Rue Frederic Combemale

City

Lille

Postcode

59000

Country

France

Scientific contact point

Organisation

Centre Oscar Lambret

Contact name

Clinical Research Sponsor Unit

Public contact point

Organisation

Centre Oscar Lambret

Contact name

Clinical Research Sponsor Unit

Locations

1 EU/EEA country · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

3 submissions — initial application plus substantial / non-substantial modifications