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.
REPOSE is an international multicenter, open-label, single arm phase II clinical trial designed to evaluate the efficacy of repotrectinib in patients with ROS1-positive NSCLC with BM. Upon meeting all selection criteria, a total of 20 participants confirmed ROS1 rearrangement will be enrolled. Participants who have received prior chemotherapy, immunotherapy or other non-ROS1 tyrosine kinase inhibitor (TKI) are eligible. Patients will continue study treatment until end of treatment (EoT) defined as the date of disease progression, death, or discontinuation from the study treatment for any other reason. After study treatment discontinuation, all participants will undergo a safety visit (at 28 ± 7 days after last treatment dose) in order to follow up toxicities and changes in concomitant medication. Patients discontinuing the study treatment at any time will enter a post-treatment follow-up period during which survival and subsequent anticancer therapy information will be collected every 3 months (± 7 days) from the safety visit until death, lost to follow-up, elective withdrawal from the study, or the end of study (EoS), whichever occurs first. Patients who discontinue treatment without evidence of disease progression will be also followed for tumor assessments until documented progression, elective withdrawal from the study, the start of new anti-cancer treatment, or the EoS. EoS is estimated to occur approximately 13 months after the last patient included in the study initiates repotrectinib treatment, unless consent withdrawal, patient is lost to follow-up, death, or premature termination of the study. EoS is defined as the last data collection point at the last participant's safety visit and will occur after the study treatment termination of the last patient in the study. The main objective of REPOSE study is to determine the efficacy of repotrectinib at any timepoint during the study period as determined locally by best central nervous system (CNS) response, that is in terms of intracranial objective response rate (IC-ORR).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Repotrectinib 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.
Medizinische Universität Graz
Graz, Austria
RECRUITINGMedical University of Vienna
Vienna, Austria
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.
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.
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.
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.
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Hospital de Vinalopó
Elche, Alicante, Spain
RECRUITINGUOMI Cancer Center
Barcelona, Barcelona, Spain
RECRUITINGHospital Universitari Vall d'Hebron
Barcelona, Barcelona, Spain
RECRUITINGInstitut Català d' Oncologia Girona (ICO)
Girona, Girona, Spain
RECRUITINGHospital Beata María Ana
Madrid, Madrid, Spain
RECRUITINGHospital Universitari Sant Joan de Reus
Reus, Tarragona, Spain
RECRUITINGHospital General Universitario Dr. Balmis
Alicante, Spain
RECRUITINGHospital de Cruces
Barakaldo, Spain
RECRUITING...and 5 more locations
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.
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.
Objective Response Rate for extracranial (EC) and overall lesions (EC-ORR)
To assess the efficacy in terms of EC-ORR at any timepoint defined as the rate of patients with partial response (PR) or complete response (CR) for EC and overall lesions, as determined locally by the investigator using Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v.1.1) 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.
CBR for EC and overall lesions
To assess the efficacy in terms of CBR at any timepoint defined as the rate of patients with objective response (CR or PR), or SD for EC and overall lesions, for at least 24 weeks, as determined locally by the investigator using RECIST v.1.1
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.
DCR for EC and overall 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 EC and overall lesions, as determined locally by the investigator using RECIST v.1.1
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.
TTR for EC and overall 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 EC and overall lesions, as determined locally by the investigator using RECIST v.1.1
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.
DoR for EC and overall 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 EC and overall lesions, as determined locally by the investigator using RECIST v.1.1.
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.
Best percentage of change in tumor burden
To evaluate the best percentage of change in tumor burden determined locally by the investigator using RANO-BM criteria for IC lesions and RECIST v.1.1 for EC and overall lesions.
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.
Progression-Free Survival (PFS)
To assess the PFS, defined as the period from treatment initiation to the first occurrence of disease progression or death from any cause, whichever occurs first, determined locally per RANO-BM criteria for IC lesions and RECIST criteria v.1.1 for EC and overall lesions.
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.
Overall Survival (OS)
To determine the OS, defined as the period from treatment initiation to death from any cause, determined locally by the investigator.
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.
Neurologic function
To assess the patient neurologic function with the Neurologic Assessment in Neuro-Oncology (NANO) scale
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.
Quality of life (QoL) with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-30)
To evaluate changes from baseline and during repotrectinib treatment in terms of patient-reported outcome (PRO) assessments of QoL and treatment-related symptoms as measured by EORTC QLQ-C30 scale. EORTC QLQ-C30 scale aims to measure cancer patients' physical, psychological and social functions. Scale and single items are transformed into scores ranging from 0 to 100. A high score for a functional scale represents a high level of functioning, whereas a high score for a symptom scale/single item represents a high level of symptomatology.
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.
QoL with the brain cancer specific questionnaire (QLQ-C20).
To evaluate changes during repotrectinib treatment in terms of PRO assessments of QoL and treatment-related symptoms as measured by EORTC QLQ-C20 scale. EORTC QLQ-BN20 brain specific tool aims to measure the effects of brain tumors and its treatment on symptoms, functions and health-related quality of life. Scale and single items are transformed into scores ranging from 0 to 100. A high score for a functional scale represents a high level of functioning, whereas a high score for a symptom scale/single item represents a high level of symptomatology.
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.
Safety and tolerability
To evaluate the safety and toxicity profile of treatment with of repotrectinib as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
Time frame: Through study completion, an average of 13 months.