A Study of Entrectinib (RXDX-101) in Pediatrics with Locally Advanced or Metastatic Solid or Primary CNS Tumors and/or Who Have No Satisfactory Treatment Options
- Conditions
- Solid tumors and primary central nervous system (CNS) tumorsMedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 100000004864MedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-001155-39-GB
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 68
- Age: Male or female from birth to age > 18 years.
Disease status:
- Phase 1 portion (closed): Patients must have measurable or evaluable disease
- Phase 2 portion:
– Parts B and D:Patients must have measurable or evaluable disease
- Part C (closed): Patients must have measurable or evaluable disease
– Part E (closed): Patients must have measurable or evaluable disease and will be assessed according to tumor type
- 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-certified or equivalently-accredited diagnostic laboratory, or centrally by a Foundation Medicine Clinical Trial Assay or the alternative, approved central laboratory for that region::
o Phase 1 portion:
– Part A: Relapsed or refractory extracranial solid tumors
o Phase 2 portion:
– Part B: Primary brain tumors with NTRK1/2/3 or ROS1 gene fusions
– Part D: Extracranial solid tumors with NTRK1/2/3 or ROS1 gene fusions
- Histologic/molecular diagnosis of malignancy at diagnosis or the time of relapse
- 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
- Performance status: Lansky or Karnofsky score >= 60% and minimum life expectancy of at least 4 weeks
- Prior therapy: Patient’s must have a a disease that is locally advanced, metastatic, or where
surgical resection is likely to result in severe morbidity, and who have no satisfactory treatment options for solid tumors and primary CNS tumors that are neurotrophic tyrosine receptor kinase (NTRK) or ROS1 fusion-positive.Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to enrollment
- Adequate bone marrow, liver, renal, cardiac and neurologic function
- Females of childbearing potential must have a negative serum pregnancy test during screening and be neither breastfeeding nor intending to become pregnant during study participation and in the following 90 days after discontinuation of study treatment
- For male patients with a female partner of childbearing potential or a pregnant female partner: Agreement to remain abstinent or use a condom during the treatment period and for at least 3 months after the last dose of study drug
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
Are the trial subjects under 18? yes
Number of subjects for this age range: 50
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
- Current participation in another therapeutic clinical trial
- Known congenital long QT syndrome
- History of recent (3 months) symptomatic congestive heart failure or ejection fraction =50% at screening
- Known active infections (bacterial, fungal, or viral) - Familial or personal history of congenital bone disorders, bone metabolism alterations or osteopenia
- Receiving Enzyme Inducing Antiepileptic Drugs
- All Phase 2 patients: Prior treatment with approved or investigational tyrosine receptor kinase inhibitor (TRK) or ROS1 inhibitors
- Patients with known hypersensitivity to entrectinib or any of the other excipients of the investigational medicinal product
- Patients with NB with bone marrow space-only disease
- Incomplete recovery from acute effects of any surgery prior to treatment
- Active gastrointestinal disease or other malabsorption syndromes that would impact drug absorption
- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or entrectinib administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry in to this study or could compromise protocol objectives in the opinion of the Investigator and/or Sponsor
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method