Testing Oral repotrectinib for locally advanced solid tumors

Inclusion

• +Documented genetic ROS1 point mutation, fusion, or amplification or NTRK1-3 fusion as identified by local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) is required.
• +Phase 1Phase 1The earliest stage of human testing, in a small group, focused on safety.Read more →: Age \<12 years; Phase 2Phase 2A middle-stage study looking at what a treatment does and watching for side effects.Read more →: Age 12- 25 years
• +Any potential allergies to repotrectinib and/or its excipients.
• +CohortCohortA group of participants sharing a characteristic, followed together.Read more → 1: Subjects with NTRK fusion gene positive (NTRK+) advanced solid tumors (including primary CNS tumors), that are tropomyosin receptor kinase (TRK) TKI naïve;
• +Cohort 2: subjects with NTRK+ advanced solid tumors (including primary CNS tumors), that are TRK TKI pre-treated;
• +Cohort 3: subjects with advanced solid tumors with ROS1 gene fusions or other ROS1 aberrations (including amplifications and point mutations) with measurable disease.
• +Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 7 days prior to enrollmentEnrolmentThe number of participants a study plans to include, or has included.Read more →.
• +Known active infections requiring ongoing treatment (bacterial, fungal, viral including HIV positivity).
• +Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse EventsAdverse eventAny medical problem that happens during a study, whether or not the treatment caused it.Read more → (NCI CTCAE) Version 4.03 Grade less than or equal to 1.
• +All subjects must have measurable disease by RECIST v1.1 or Response Assessment in Neuro-Oncology (RANO) criteria at time of enrollment.
• +Subjects must have a Lansky (\< 16 years) or Karnofsky (≥ 16 years) score of at least 50.
• +Life expectancy greater than or equal to 12 weeks, in the investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →'s opinion.
• +Adequate hematologic, renal and hepatic function.
• +Phase 2 Inclusion CriteriaInclusion criteriaThe things you must have or be for a study to consider you.Read more →:
• +Cohort Specific Inclusion Criteria:
• +Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment.
• +Key Exclusion CriteriaExclusion criteriaThe things that would prevent someone from taking part.Read more → (Phase 1 and Phase 2):
• +Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
• +Gastrointestinal disease (e.g., Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact drug absorption.
• +Any of the following cardiac criteria:
• +Mean resting corrected QT interval (ECG interval measured from the onset of the QRS complex to the end of the T wave) for heart rate (QTc) \> 480 msec obtained from three ECGs, using the screeningScreeningThe checks done before joining, to see whether a study fits.Read more → clinic ECG machine-derived QTc value
• +Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., 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, congenital long QT syndrome, family history of long QT syndrome, or any concomitant medication known to prolong the QT interval
• +Peripheral neuropathy of CTCAE ≥grade 2.
• +Subjects being treated with or anticipating the need for treatment with strong CYP3A4 inhibitors or inducers.
• +Prior cytotoxic chemotherapy is allowed.
• +Prior immunotherapy is allowed.
• +Major surgery within 14 days (2 weeks) of start of repotrectinib treatment. Central venous access (Broviac, Mediport, etc.) placement does not meet criteria for major surgery.