A Study of Repotrectinib in Pediatric and Young Adult Subjects Harboring ALK, ROS1, OR NTRK1-3 Alterations
Locally Advanced Solid Tumors, Metastatic Solid Tumors, Lymphoma
About this trial
This is an interventional treatment trial for Locally Advanced Solid Tumors focused on measuring ALK, ROS1, NTRK1-3, Primary CNS tumor, anaplastic large cell lymphoma, metastatic solid tumor, advanced solid tumor, sarcoma, infantile fibrosarcoma, glioblastoma, soft tissue schwannoma, solitary fibrous tumor, glioma, inflammatory myofibroblastic tumor, pediatric
Eligibility Criteria
Key Inclusion Criteria:
- Documented genetic ALK, ROS1, or NTRK1-3 alteration (point mutation, fusion, amplification) 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 1: Age <12 years; Phase 2: Age 12- 25 years
- Prior cytotoxic chemotherapy is allowed.
- Prior immunotherapy is allowed.
- Resolution of all acute toxic effects (excluding alopecia) of any prior anti-cancer therapy to National Cancer Institute Common Terminology Criteria for Adverse Events (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 Criteria (RANO) criteria at time of enrollment.
- Subjects with a primary CNS tumor or CNS metastases must be neurologically stable on a stable or decreasing dose of steroids for at least 14 days prior to 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.
- Adequate hematologic, renal and hepatic function.
Phase 2 Inclusion Criteria:
Cohort Specific Inclusion Criteria:
- Cohort 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 tumors or ALCL characterized by other ALK/ROS1/NTRK alterations or NTRK fusions without centrally confirmed measurable disease or not otherwise eligible for Cohort 1 or 2.
- Subjects in Cohorts 1 and 2 must have prospectively confirmed measurable disease by BICR prior to enrollment.
Key Exclusion Criteria (Phase 1 and Phase 2):
- Subjects with neuroblastoma with only bone marrow disease evaluable by bone marrow aspiration only.
- 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.
- Known active infections (bacterial, fungal, viral including HIV positivity).
- 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 screening 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.
Sites / Locations
- Children's Hospital Los AngelesRecruiting
- University of California at Los AngelesRecruiting
- Children's Hospital Colorado - Anschutz Medical CampusRecruiting
- Arnold Palmer Hospital For ChildrenRecruiting
- Maine Medical CenterRecruiting
- Dana Farber Cancer Institute.Recruiting
- Washington University School of Medicine in St. LouisRecruiting
- Rutgers Cancer Institute of New JerseyRecruiting
- Memorial Sloan-Kettering Cancer Center.Recruiting
- Local Institution - 2112
- Penn State Milton S. Hershey Medical CenterRecruiting
- Children'S Hospital Of PhiladelphiaRecruiting
- St. Jude Children's Research HospitalRecruiting
- The University of Texas Southwestern Medical Center - Harold C Simmons Comprehensive Cancer CenterRecruiting
- The University of Texas MD Anderson Cancer Center.Recruiting
- Children's Hospital of Richmond at VCU
- Local Institution - 6104Recruiting
- Local Institution - 6103Recruiting
- Local Institution - 6102Recruiting
- Local Institution - 6101Recruiting
- Local Institution - 2202Recruiting
- Local Institution - 2201Recruiting
- Local Institution - 4901Recruiting
- Local Institution - 6111
- Local Institution - 4203
- Local Institution - 4201
- Local Institution - 6110
- Local Institution - 6112
- Local Institution - 6109
- Local Institution - 4202
- Local Institution - 6108
- Local Institution - 4301
- Local Institution - 6113
- Local Institution - 4302
- Local Institution - 6114
- Local Institution - 6303Recruiting
- Local Institution - 6302Recruiting
- Local Institution - 6304Recruiting
- Local Institution - 6301Recruiting
- Local Institution - 6401Recruiting
- Local Institution - 6402Recruiting
- Local Institution - 4104Recruiting
- Local Institution - 6105
- Local Institution - 4103
- Local Institution - 6106
- Local Institution - 4101Recruiting
- Local Institution - 4102Recruiting
- Local Institution - 6107
- Local Institution - 6202Recruiting
- Local Institution - 6201Recruiting
Arms of the Study
Arm 1
Experimental
Repotrectinib (TPX-0005)
Phase 1 Oral repotrectinib (TPX-0005): Safety and tolerability at different dose levels Phase 2 Oral repotrectinib (TPX-0005): 3 cohorts Cohort 1: TKI-naive NTRK fusion Cohort 2: Prior TKI NTRK fusion Cohort 3: ALK/ROS1/NTRK alterations or fusions in tumors and ALCL