ENASIDENIB MESILATE for Paediatric cancer

Inclusion criteria

• {"criterion_text":"- Patients must be diagnosed with hematologic or solid tumor malignancy that has progressed or relapsed despite standard therapy, or for which no effective standard therapy exists.\n- For all oral medications patients must be able to comfortably swallow whole capsules or tablets (except for those for which an oral solution is available); nasogastric or gastrostomy feeding tube administration is allowed only if indicated.\n- Written informed consent from parents/legal representative, patient, and age-appropriate assent before any study-specific screening procedures are conducted according to local, regional or national guidelines.\n- Patient affiliated to a social security regimen or beneficiary of the same according to local requirements.\n- For a complete list of eligibility criteria, see the sections corresponding to inclusion and exclusion criteria in the protocol.\n- Age <18 years at inclusion.\n- Patient must have had advanced molecular profiling (i.e. WES/WGS +/- RNAseq) of their recurrent or refractory tumor i.e. at the time of disease progression/relapse; exceptionally patients with advanced molecular profiling at diagnosis may be allowed.\n- Evaluable or measurable disease as defined by standard imaging criteria for the patient’s tumor type.\n- Performance status: Karnofsky performance status (for patients >12 years of age) or Lansky Play score (for patients ≤12 years of age) ≥70%.\n- Life expectancy ≥3 months.\n- Adequate organ function as defined in section 3.1.1 of the protocol.\n- Able to comply with scheduled follow-up and with management of toxicity.\n- Females of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to initiation of treatment. Sexually active patients must agree to use highly effective method of contraception."}

Exclusion criteria

• {"criterion_text":"- Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or require increasing doses of corticosteroids or local CNS-directed therapy to control their CNS disease.\n- Major surgery within 21 days of the first dose.\n- Currently taking medications with a known risk of prolonging the QT interval or inducing Torsades de Pointes.\n- Known hypersensitivity to any study drug or component of the formulation.\n- Pregnant or nursing (lactating) females\n- Vaccinated with live, attenuated vaccines,including yellow fever, within 4 weeks of the first dose of study drug.\n- For a complete list of eligibility criteria, see the sections corresponding to inclusion and exclusion criteria in the protocol. Additional inclusion and enrichment and exclusion criteria for each treatment arm are specified separately in protocol section 3.2.\n- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).\n- Clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias).\n- Active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection.\n- Presence of any ≥CTCAE grade 2 treatment-related toxicity with the exception of lymphopenia G3, alopecia, ototoxicity or peripheral neuropathy.\n- Systemic anticancer therapy within 21 days of the first study dose or 5 times its half-life, whichever is less.\n- Previous myeloablative therapy with autologous hematopoietic stem cell rescue within 8 weeks of the first study drug dose\n- Allogeneic stem cell transplant within 3 months prior to the first study drug dose. Patients receiving any agent to treat or prevent graft-versus host disease (GVHD) post bone marrow transplant are not eligible for this trial.\n- Radiotherapy (non-palliative) within 21 days prior to the first dose of drug (or within 6 weeks for therapeutic doses of MIBG or craniospinal irradiation).\n- Increasiong dose of Steroids over the last 7 days and with a maximum of 0.5 mg/kg /days"}

Primary endpoints

• {"endpoint_text":"- The recommended phase II dose (RP2D) will be defined as the adult recommended dose (adjusted for weight or BSA) if toxicity and PK profiling are similar in children and in adults, or a higher dose, providing it is below or equal to the maximum tolerated dose (MTD).","definition_or_measurement_approach":"RP2D defined as adult recommended dose (adjusted for weight/BSA) if toxicity and PK in children are similar to adults; otherwise a higher dose may be chosen provided it is ≤ MTD. Determination based on observed toxicity profile and pharmacokinetic (PK) parameters in pediatric patients compared to adult data."}

Secondary endpoints

• {"endpoint_text":"- The maximum tolerated dose (MTD) will be defined as the dose associated with or closest to 25% of DLTs in cycle 1.","definition_or_measurement_approach":"MTD defined as dose associated with (or closest to) 25% dose limiting toxicities (DLTs) in cycle 1."}
• {"endpoint_text":"- Dose Limiting Toxicities (DLT) will be defined using NCI CTCAE v4.03.","definition_or_measurement_approach":"DLTs graded/defined according to NCI CTCAE v4.03 criteria."}
• {"endpoint_text":"- Overall response rate (ORR) will be defined as percentage of patients achieving confirmed CR or confirmed PR as per standard methods for the underlying disease.","definition_or_measurement_approach":"ORR = percentage of patients with confirmed complete response (CR) or partial response (PR) according to standard disease-specific response criteria (e.g., RECIST v1.1, RANO, INRC, or leukemia criteria as applicable)."}
• {"endpoint_text":"- Duration of response (DOR) will be defined as the time period between the first documented response (PR or CR) and the time of first documented progression (clinically or radiologically – Appendix 3 to 7) or death from any cause, whichever comes first. Duration of response for patients free of progression at the cut-off date will be censored at the last assessment date.","definition_or_measurement_approach":"DOR = time from first documented confirmed response to first documented progression or death; censoring at last assessment date for patients without progression at cut-off."}
• {"endpoint_text":"- Progression-free survival (PFS) will be defined as the time from treatment initiation until the date of first documented progression or death from any cause, whichever comes first. Patients alive and free of progression at the cut-off date will be censored at the last assessment date.","definition_or_measurement_approach":"PFS = time from treatment start to first documented progression or death; censoring at last assessment for those alive without progression at cut-off."}
• {"endpoint_text":"- Overall survival (OS) will be defined as the time from treatment initiation until the date of death from any cause. Patients alive at the cut-off date will be censored at the date of last news.","definition_or_measurement_approach":"OS = time from treatment start to death from any cause; censor at date of last contact for survivors."}
• {"endpoint_text":"- Adverse events according to the NCI CTCAE V4.03 in all cycles of treatment.","definition_or_measurement_approach":"Adverse events graded and recorded per NCI CTCAE v4.03 across all treatment cycles."}
• {"endpoint_text":"- PK parameters, including but not limited to plasma concentration time profiles, AUClast, AUCtau, Cmin, Cmax, Tmax, Clearance, Half-life time.","definition_or_measurement_approach":"Pharmacokinetic parameters measured from plasma sampling time profiles including AUClast, AUCtau, Cmin, Cmax, Tmax, clearance, half-life, etc."}
• {"endpoint_text":"- Relationship between the molecular profile of the tumor samples, circulating tumor DNA and tumor growth.","definition_or_measurement_approach":"Exploratory analyses correlating tumor molecular profile (from WES/WGS +/- RNAseq), circulating tumor DNA measures and tumor growth metrics."}

Netherlands

Earliest CTIS Part Ii Submission Date

27-09-2024

Latest Decision Or Authorization Date

02-02-2026

Processing Time Days

493

Number Of Sites

1

Number Of Participants

23

Denmark

Earliest CTIS Part Ii Submission Date

19-09-2024

Latest Decision Or Authorization Date

30-01-2026

Processing Time Days

498

Number Of Sites

1

Number Of Participants

26

France

Earliest CTIS Part Ii Submission Date

21-09-2024

Latest Decision Or Authorization Date

28-01-2026

Processing Time Days

494

Number Of Sites

10

Number Of Participants

276

Italy

Earliest CTIS Part Ii Submission Date

25-09-2024

Latest Decision Or Authorization Date

04-02-2026

Processing Time Days

497

Number Of Sites

3

Number Of Participants

25

Spain

Earliest CTIS Part Ii Submission Date

18-09-2024

Latest Decision Or Authorization Date

02-02-2026

Processing Time Days

502

Number Of Sites

3

Number Of Participants

48

Primary sponsor

Full Name

Institut Gustave Roussy

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"Denmark","full_name":"Frederiksberg Hospital","duties_or_roles":"1","organisation_type":"Hospital/Clinic/Other health care facility"}