Repotrectinib in ROS1-positive Non-small Cell Lung Cancer Patients With Active Brain Metastasis
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorMedSIR
About this trial
REPOSE is a phase II clinical trial exploring the safety and efficacy of repotrectinib in patients with non-small cell lung cancer (NSCLC) characterized by the presence of brain metastasis (BM) and whose tumors have mutated ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) gene.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patient must be capable to understand the purpose of the study and have signed written informed consent form (ICF) prior to beginning specific protocol procedures.
Female or male patients ≥ 18 years of age at the time of signing ICF.
Patients must be capable to swallow capsules intact (without chewing, crushing, or opening).
Histologically documented NSCLC.
Disqualifiers
Major surgery within four weeks of the start of treatment.
Type I leptomeningeal disease per ESMO-EANO guidelines.
Have received prior radiotherapy within two weeks before the first dose of Study treatment (four weeks in case of radiation therapy of the central nervous system). Participants must have recovered from all radiation-related toxicities, not require steroids, and not have had radiation pneumonitis.
Treatment with approved or investigational cancer therapy within14 days prior to initiation of Study treatment.
Trial design
Design model
Single group
Treatments tested in this trial
Repotrectinib
DrugRepotrectinib is administered orally in capsule form, with each capsule containing size 0 hard gelatin 40 mg of the active compound in bottles containing 30 capsules. Repotrectinib is administered orally in the form of capsules. The capsules are taken by mouth and swallowed intact (without chewing, crushing, or opening) with water or another suitable liquid.
Treatment groups
20 Participants
are divided into 1 treatment groupGroup A: RepotrectinibExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Intracranial Objective Response Rate (IC-ORR)
To assess the efficacy in terms of IC-ORR at any timepoint defined as the rate of patients with partial response (PR) or complete response (CR) for IC lesions, as determined locally by the investigator as judged by best CNS response according to the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria.
Time frame
From date of inclusion until the date of first documented progression or date of death from any cause or treatment discontinuation from any other reason, whichever came first, assessed through study completion, an average of 13 months.Secondary outcomes
1
Clinical Benefit Rate (CBR) for intracranial (IC) lesions
To assess the efficacy in terms of CBR, defined as the rate of patients with objective response (CR or PR), or stable disease (SD) for IC lesions for at least 24 weeks, as determined locally by the investigator using RANO-BM.
Time frame
From date of inclusion until the date of first documented progression or date of death from any cause or treatment discontinuation from any other reason, whichever came first, assessed through study completion, an average of 13 months.2
Disease Control Rate (DCR) for IC lesions
To assess the efficacy in terms of DCR, defined as the percentage of patients with advanced cancer whose therapeutic intervention has led to a CR, PR, or SD for IC lesions, as determined locally by the investigator using RANO-BM.
Time frame
From date of inclusion until the date of first documented progression or date of death from any cause or treatment discontinuation from any other reason, whichever came first, assessed through study completion, an average of 13 months.3
Time to Response (TTR) for IC lesions
To assess the efficacy in terms of TTR, defined as the period from the treatment initiation to time of the first objective tumor response (tumor shrinkage of ≥ 30%) observed for patients who achieved a CR or PR for IC lesions, as determined locally by the investigator using RANO-BM.
Time frame
From date of inclusion until the date of first documented progression or date of death from any cause or treatment discontinuation from any other reason, whichever came first, assessed through study completion, an average of 13 months.4
Duration of Response (DoR) for IC lesions
To assess the efficacy in terms of DoR, defined as the period from the first occurrence of a documented objective response to disease progression or death from any cause, observed for patients who achieved a CR or PR for IC lesions, as determined locally by the investigator using RANO-BM.
Time frame
From date of inclusion until the date of first documented progression or date of death from any cause or treatment discontinuation from any other reason, whichever came first, assessed through study completion, an average of 13 months.Other outcomes
1
Exploratory endpoint: Genetic studies using blood samples to investigate the potential association with clinical outcomes
Gene expression profiling analyses performed on blood samples to investigate the potential association with clinical outcomes.
Time frame
Through study completion, an average of 13 months.2
Exploratory endpoint: ROS1 gene expression analysis using baseline tissue samples to investigate the potential association with clinical outcomes
ROS1 gene expression analysis performed on baseline tumor tissue samples to investigate the potential association with clinical outcomes.
Time frame
Through study completion, an average of 13 months.3
Exploratory endpoint: Analysis of medical imaging to identify potential biomarkers associated with clinical outcomes
Analysis of oncological biomarkers, such as growth rate of tumor derived by tumor growth rate modeling or tumor heterogeneity according to quantitative estimation through radiomics, may be performed on radiological images to investigate the potential association with clinical outcomes.
Time frame
Through study completion, an average of 13 months.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
MedSIR
Lead sponsor
Medical University of Vienna
Collaborator
Source ClinicalTrials.gov