ENTRECTINIB for Pediatric solid tumors | Primary central nervous system (CNS) tumors

Inclusion criteria

• {"criterion_text":"- Sex and age: male or female aged from birth to age < 18 years"}
• {"criterion_text":"- Disease status: Phase 1 portion (closed): Patients must have measurable or evaluable disease Phase 2 portion: Cohort B: Patients must have measurable or evaluable disease as defined by RANO Cohort C (closed) and D: Patients must have measurable or evaluable disease as defined per RECIST v1.1±Curie Scale Cohort D: Patients must have measurable or evaluable disease, Cohort E (closed): Patients must have measurable or evaluable disease and be assessed according to tumor type as defined per RECIST v1.1±Curie Scale or RANO"}
• {"criterion_text":"- Tumor types included below harboring NTRK1/2/3 or ROS1 gene fusions as determined locally by an appropriately validated assay performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalently-accredited diagnostic laboratory, or centrally by a Foundation Medicine Clinical Trial Assay or the alternative, approved central laboratory for that region: Phase 1 portion: Cohort A: Relapsed or refractory extracranial solid tumors Phase 2 portion: Cohort B: Primary brain tumors with NTRK1/2/3 or ROS1 gene fusions Cohort D: Extracranial solid tumors with NTRK1/2/3 or ROS1 gene fusions"}
• {"criterion_text":"- Histologic/molecular diagnosis of malignancy at diagnosis or the time of relapse"}
• {"criterion_text":"- For patients enrolled via local molecular testing, an archival tumor tissue from diagnosis or, preferably, from relapsed disease is required to be submitted for independent central testing at Foundation Medicine, Inc. laboratory or the alternative, approved central assay laboratory for that region"}
• {"criterion_text":"- Performance status: Lansky or Karnofsky score ≥ 60% and minimum life expectancy of at least 4 weeks"}

Exclusion criteria

• {"criterion_text":"- Current participation in another therapeutic clinical trial"}
• {"criterion_text":"- Known congenital long QT syndrome"}
• {"criterion_text":"- History of recent (3 months) symptomatic congestive heart failure or ejection fraction ≤50% at screening"}
• {"criterion_text":"- Known active infections (bacterial, fungal, or viral)"}
• {"criterion_text":"- All Phase 2 patients: Prior treatment with approved or investigational tyrosine receptor kinase inhibitor (TRK) or ROS1 inhibitors"}
• {"criterion_text":"- Incomplete recovery from acute effects of any surgery prior to treatment"}

Primary endpoints

• {"endpoint_text":"- 1. Dose limiting toxicity DLT during the first cycle (28 days) in pediatric patients with relapsed or refractory solid tumors using the F1 formulation (and subsequently using F06, minitablets). The RP2D will be determined from DLT derived from clinical and laboratory observations in the first treatment cycle according to the NCI CTCAE v4.03 that is related to entrectinib)","definition_or_measurement_approach":"DLT assessed during first 28-day cycle using NCI CTCAE v4.03; RP2D determined from DLTs derived from clinical and laboratory observations in cycle 1."}
• {"endpoint_text":"- 2. Objective response rate as assessed by the BICR will be evaluated in the efficacy evaluable population from the Phase II dose expansion cohorts (Cohort B and D)","definition_or_measurement_approach":"ORR assessed by Blinded Independent Central Review (BICR) in efficacy-evaluable patients from Phase II dose expansion cohorts (Cohorts B and D)."}

Secondary endpoints

• {"endpoint_text":"- 1. Incidence and severity of adverse events, laboratory and electrocardiogram (ECG) abnormalities","definition_or_measurement_approach":"Safety assessed by incidence and severity of AEs, laboratory abnormalities, and ECG changes."}
• {"endpoint_text":"- 2. Maximal plasma concentration (Cmax) of entrectinib (F1, F06 given intact, F06 administered via feeding tube, and minitablets)","definition_or_measurement_approach":"Pharmacokinetic measure Cmax for listed formulations and administration methods."}
• {"endpoint_text":"- 3. Time of maximal plasma concentration (Tmax) of entrectinib (F1, F06 given intact, F06 administered via feeding tube, and minitablets)","definition_or_measurement_approach":"Pharmacokinetic measure Tmax for listed formulations and administration methods."}
• {"endpoint_text":"- 4. Area under the plasma concentration vs. time curve (AUC) of entrectinib (F1, F06 given intact, F06 administered via feeding tube, and minitablets)","definition_or_measurement_approach":"Pharmacokinetic measure AUC for listed formulations and administration methods."}
• {"endpoint_text":"- 5. ORR in the efficacy evaluable and safety evaluable populations","definition_or_measurement_approach":"Objective response rate measured in efficacy-evaluable and safety-evaluable populations."}
• {"endpoint_text":"- 6. DOR and TTR as assessed by BICR and the investigator in the efficacy evaluable and safety evaluable populations:","definition_or_measurement_approach":"Duration of response (DOR) and time to response (TTR) assessed by BICR and investigator."}
• {"endpoint_text":"- 7. ORR, TTR, DOR in the efficacy evaluable and safety evaluable populations as assessed by BICR and the investigator with use of RECIST v1.1, RANO, and the Curie scale, as applicable","definition_or_measurement_approach":"Efficacy endpoints assessed using RECIST v1.1, RANO, and Curie scale as applicable, by BICR and investigator."}
• {"endpoint_text":"- 8. CBR and PFS in the efficacy evaluable and safety evaluable populations as assessed by BICR and investigator with use of RECIST v1.1, RANO, and the Curie scale, as applicable","definition_or_measurement_approach":"Clinical benefit rate (CBR) and progression-free survival (PFS) assessed by BICR and investigator using specified response criteria."}
• {"endpoint_text":"- 9. OS in the efficacy evaluable and safety evaluable populations","definition_or_measurement_approach":"Overall survival measured in efficacy-evaluable and safety-evaluable populations."}
• {"endpoint_text":"- 10. Assessment of growth (weight, height), puberty (Tanner), neurological function and neurocognitive function of patients on treatment","definition_or_measurement_approach":"Growth, pubertal staging (Tanner), neurological and neurocognitive function assessments during treatment."}
• {"endpoint_text":"- 11. Acceptability and palatability assessment for F06 capsules and minitablets formulation","definition_or_measurement_approach":"Assessment of acceptability and palatability for F06 capsules and minitablet formulations."}

France

Earliest CTIS Part Ii Submission Date

27-05-2024

Latest Decision Or Authorization Date

17-07-2025

Processing Time Days

416

Number Of Sites

2

Number Of Participants

9

Germany

Earliest CTIS Part Ii Submission Date

23-04-2024

Latest Decision Or Authorization Date

17-07-2025

Processing Time Days

451

Number Of Sites

1

Number Of Participants

1

Italy

Earliest CTIS Part Ii Submission Date

23-04-2024

Latest Decision Or Authorization Date

17-07-2025

Processing Time Days

451

Number Of Sites

1

Number Of Participants

8

Spain

Earliest CTIS Part Ii Submission Date

23-04-2024

Latest Decision Or Authorization Date

21-07-2025

Processing Time Days

455

Number Of Sites

2

Number Of Participants

7

Primary sponsor

Full Name

F. Hoffmann-La Roche AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

IQVIA Limited

Responsibilities

Global CRO, Other Third Party Duty

Name

Syneos Health Inc.

Third parties

• {"country":"United States","full_name":"Oracle America Inc.","duties_or_roles":"EDC Provider","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Foundation Medicine Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Unisphere Travel Ltd. Inc.","duties_or_roles":"Patient Reimbursement","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"Median Technologies","duties_or_roles":"other","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q Squared Solutions LLC","duties_or_roles":"Specialty Laboratory","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Belgium","full_name":"CellCarta","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Global CRO, Other Third Party Duty","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labconnect LLC","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}