Phase 1/2 Open Label solid tumour Safety and Tolerability study inPediatric and Young Adult subjects.
- Conditions
- Advanced solid tumorsMedDRA version: 21.1Level: LLTClassification code: 10065252Term: Solid tumor Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-506464-14-00
- Lead Sponsor
- Turning Point Therapeutics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 63
For Phase 2: EU will not enroll subjects in Cohort 1. Cohort 2: Subjects with NTRK+ advanced solid tumors (including primary CNS tumors), TRK TKI-pretreated. Nonresponse, disease progression or intolerability to at least 1 but no more than 2 prior TRK TKIs. Any prior lines are allowed. Subjects must have prospectively confirmed measurable disease by BICR prior to enrollment. Cohort 3: the EU: (1) will only enroll subjects with ROS1 gene fusions. •Documented genetic ROS1 or NTRK1-3 alteration as identified by local testing in a CLIA laboratory in the US or equivalent. •For subjects enrolled per tissue-based test, adequate tumor tissue should be sent prior to enrollment to the central lab. If archived tumor tissue is not available, a fresh biopsy should be obtained. For subjects enrolled by liquid biopsy test; blood samples should be sent prior to enrollment to the central lab., Screening Local laboratory values: ANC=1.5 × 109/L, =0.75 × 109L, if known bone marrow involvement PLT =100 × 109/L independent of platelets transfusion support for at least 7 days prior to dosing, =50 × 109/L, if known bone marrow involvement Hemoglobin= 8.0 g/dL independent of red blood cell transfusion support for at least 7 days prior to dosing, unless bone marrow involvement identified at enrollment Serum creatinine or creatinine clearance* Within normal limits per age or creatinine clearance or nuclear GFR>40 mL/min Total serum bilirubin < 1.5 × ULN AST/ALT<2.5 × ULN; <5 × ULN if liver metastases are present ALP <2.5 × ULN; <5 × ULN if liver and/or bone metastasis are present. Serum calcium, magnesium, and potassium: Normal or =CTCAE grade 1 with or without supplementation. •?Serum Creatinine by Age Age < 6 years - Maximum Serum Creatinine (mg/dL) – Male: 0,8 - Female: 0,8 / Maximum Serum Creatinine (µmol/L) – Male: 71 Female: 71 Age 6 to < 10 years - Maximum Serum Creatinine (mg/dL) – Male: 1 - Female: 1 / Maximum Serum Creatinine (µmol/L) – Male: 88 - Female: 88 Age 10 to < 13 years - Maximum Serum Creatinine (mg/dL) – Male: 1.2 - Female: 1.2 / Maximum Serum Creatinine (µmol/L) – Male: 106 - Female: 106 Age 13 to < 16 years - Maximum Serum Creatinine (mg/dL) – Male: 1,5 - Female: 1,4 / Maximum Serum Creatinine (µmol/L) – Male: 132 - Female: 124 Age = 16 years - Maximum Serum Creatinine (mg/dL) – Male: 1,7 - Female: 1,4 / Maximum Serum Creatinine (µmol/L) – Male: 150 - Female: 124, Reproductive Status: For female and male participants, see Protocol Section 5.1 for the full list of criteria., The subject, parent or guardian must voluntarily sign and date an informed consent approved (in addition to pediatric assent, if required) by an IEC, prior to the initiation of any study specific procedures., Age: ? Phase 1: Age < 12 years (age at Cycle 1 Day 1) ? Phase 2: Up to age 25 years (age at Cycle 1 Day 1). While the Phase 1 dose escalation is ongoing, subjects 12 years of age and above may be enrolled directly in the Phase 2 part of the study. Subjects age < 12 years of age will be enrolled in the Phase 2 part after determination of the pediatric RP2D in Phase 1., Ability to comply with outpatient visits, laboratory testing, and study procedures during study participation., Subjects must have recovered from the acute toxic effects of all previous therapies prior to study enrollment to CTCAE v4.03 criteria = grade 1, with the exception of alopecia. Subjects must not have received the therapies indicated below for the specified time period: •Chemotherapy: Last do
Concurrent participation in another therapeutic clinical trial., Subjects being treated with or anticipating the need for treatment with strong cytochrome P450 (CYP)3A4 inhibitors or inducers as listed in Appendix 4., Any potential allergies to repotrectinib and/or its excipients, Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only., Major surgery within 14 days (2 weeks) prior to Cycle 1 Day 1. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery., Subjects who are pregnant or breast feeding., Subjects with known active infections requiring ongoing treatment (bacterial, fungal, or viral, including HIV)., Subjects with gastrointestinal disease (eg, Crohn's disease, ulcerative colitis, short gut syndrome) or other malabsorption syndromes that would impact on drug absorption., Any of the following cardiac criteria: • Mean resting corrected QT interval (electrocardiogram [ECG] interval measured from the onset of the QRS complex to the end of the T wave) for heart rate > 480 msec obtained from 3 ECGs, using the screening clinic ECG machine-derived QTc value • Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (eg, complete left bundle branch block, third degree heart block, second degree heart block, PR interval >250 msec) • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval (Appendix 5), Subjects with peripheral neuropathy with CTCAE grade = 2., Subjects with other severe acute or chronic medical or psychiatric conditions or laboratory abnormalities that, per the judgement of the Investigator or Sponsor, may increase the risk associated with study participation or study drug administration, or that may interfere with the interpretation of study results, or make the subject inappropriate for entry into the study, or could compromise protocol objectives.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: Phase 2 Study<br>• Determine the antitumor activity of repotrectinib in pediatric and<br>young adult subjects with advanced or metastatic malignancies<br>harboring ROS1 or NTRK1-3 alterations.;Secondary Objective: Determine the antitumor activity in terms of DOR, overall survival (OS) and progression-free survival (PFS) following treatment with repotrectinib, Determine intracranial antitumor activity of repotrectinib, Evaluate the safety and tolerability of repotrectinib at the pediatric RP2D, Characterize the PK of repotrectinib at the pediatric RP2D;Primary end point(s): ORR as determined by BICR
- Secondary Outcome Measures
Name Time Method Secondary end point(s):DOR, TTR and CBR;Secondary end point(s):Intracranial tumor response;Secondary end point(s):Central nervous system (CNS) progression-free survival (CNS-PFS) in subjects with measurable brain metastases;Secondary end point(s):PFS and OS;Secondary end point(s):PK parameters;Secondary end point(s):Type, incidence, severity, timing, seriousness, and relatedness of AEs and laboratory abnormalities