LAROTRECTINIB SULFATE for High-grade glioma | Diffuse intrinsic pontine glioma (DIPG)

Inclusion criteria

• {"criterion_text":"- Age: Patients ≤ 21 years of age (birth to 21 years of age excluding preterm newborn infants) at the time of study enrollment will be eligible.\n- Organ function requirement: Adequate neurologic function defined as: • Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled.\n- Informed consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.\n- Diagnosis: Patients with newly-diagnosed HGG, including DIPG, whose tumors are documented in a CLIA/CAP certified lab (or clinically equivalent method considered standard in non-US sites) to harbor an NTRK fusion alteration by FISH, PCR, or next generation sequencing are eligible. Patients must have had histologically verified HGG such as anaplastic astrocytoma, glioblastoma, or H3 K27-mutant diffuse midline glioma verified at a CONNECT site.\n- Disease status: Patients with disseminated DIPG or HGG are eligible only if the patient is to receive chemotherapy only, i.e. no craniospinal RT is intended to be given. MRI of spine must be performed if disseminated disease is suspected clinically by the treating physicians. Patients with primary spinal tumors are eligible only if the patient is to receive either chemotherapy or focal radiation therapy, i.e. no craniospinal RT is intended to be given. Patients with leptomeningeal disease only, with no definitive identifiable primary tumor, and documented NTRK fusion, must be discussed with the Study Chair on a case-by-case basis.\n- Performance level: Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50% for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n- Prior therapy: • Patients must not have received any prior anti-cancer chemotherapy, • Prior use of corticosteroids is allowed\n- Organ function requirement: Adequat bone marrow function defined as: • Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3, • Platelet count ≥ 100,000/μl (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment), • Hemoglobin >8 g/dL (may receive transfusions)\n- Organ function requirement: Adequate renal function defined as: • Serum creatinine within normal institutional limits, OR • Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2\n- Organ function requirement: Adequate liver function defined as: • Total bilirubin ≤ 2.5 × institutional upper limit of normal, • AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional upper limit of normal\n- Organ function requirement: Adequate pulmonary function defined as: • Pulse oximetry > 94% on room air if there is clinical indication for determination (e.g. dyspnea at rest)"}

Exclusion criteria

• {"criterion_text":"- Pregnancy or breast-feeding: Pregnant or breast-feeding women will not be entered on this study due to unknown risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.\n- Minors who will not be capable of giving consent when they reach the legal age of majority\n- Concomitant medications: Investigational Drugs: Patients who have previously received or are currently receiving another investigational drug are not eligible. Anti-cancer Agents: Patients who have previously received or are currently receiving other anti-cancer agents, including chemotherapy, immunotherapy, monoclonal antibodies, biologic or targeted therapy, are not eligible.\n- Infection: Patients must not have any active, uncontrolled systemic bacterial, viral or fungal infection.\n- Patients who have received prior solid organ transplantation are not eligible.\n- Patients must not have malabsorption syndrome or other condition affecting oral absorption.\n- Patients must not be receiving any treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or inducer. Strong inducers or inhibitors of CYP3A4 should be avoided from 7 days prior to enrollment to the end of the study.\n- Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.\n- Patient committed to an institution by virtue of an order issued either by the judicial or the administrative authorities\n- Patient is dependent on the Sponsor, Investigator or trial site"}

Primary endpoints

• {"endpoint_text":"- Disease control rate (CR, CCR, PR, SD) presented as frequency and percentage. Time frame: At the end of cycle 2","definition_or_measurement_approach":"Disease control rate defined as proportion of participants with Complete Response (CR), Continued Complete Response (CCR), Partial Response (PR) or Stable Disease (SD); presented as frequency and percentage; measured at end of cycle 2."}
• {"endpoint_text":"- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0. Time frame: From Day 1 of Course 1 of combination treatment with chemotherapy/ from Day 1 of treatment after radiotherapy through 30 days following end of protocol treatment","definition_or_measurement_approach":"Count of participants experiencing treatment-related adverse events graded by CTCAE v5.0; time frame from Day 1 of Course 1 of combination treatment or from Day 1 after radiotherapy through 30 days post end of protocol treatment."}

Germany

Earliest CTIS Part Ii Submission Date

24-04-2024

Latest Decision Or Authorization Date

09-04-2026

Processing Time Days

715

Number Of Sites

5

Number Of Participants

5

Primary sponsor

Full Name

Nationwide Childrens Hospital

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

United States

Third parties

• {"country":"Germany","full_name":"Universitaetsklinikum Heidelberg AöR","duties_or_roles":"safety reporting to CTIS/EudraVigilance and monitoring of German sites by KKS","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Universitaetsklinikum Heidelberg AöR","duties_or_roles":"CTIS submission by KiTZ Clinical Trial Group","organisation_type":"Hospital/Clinic/Other health care facility"}