stop_circleTerminated/Withdrawn
Carcinoma, Non-Small-Cell Lung
Bayer Identifier:
19781
ClinicalTrials.gov Identifier:
EudraCT Number:
EU CT Number:
Not Available
Study to test the safety and how radium-223 dichloride an alpha particle-emitting radioactive agent works in combination with pembrolizumab an immune checkpoint inhibitor in patients with stage IV non-small cell lung cancer with bone metastases
Trial purpose
The purpose of the study was to determine the safety and test the efficacy of the combination of radium-223 dichloride and pembrolizumab in patients with stage IV non-small cell lung cancer (NSCLC) with bone metastases who either had not received any systemic therapy for their advanced disease or had progressed on prior immunologic checkpoint blockade with antibodies against the programmed cell death protein-(ligand) 1 (PD-1/PD-L1). In this study researchers wanted to measure tumor shrinkage in response to treatment and how long that shrinkage lasted and gathered information on safety. Pembrolizumab is an immunologic checkpoint blocker that promotes an immune response against the tumor. Radium-223 dichloride is an alpha particle-emitting radioactive agent which kills cancer cells.
Key Participants Requirements
Sex
AllAge
18 - N/ATrial summary
Enrollment Goal
8Trial Dates
March 2020 - January 2023Phase
Phase 1Could I Receive a placebo
NoProducts
Radium-223 dichloride+pembrolizumab (BAY88-8223)Accepts Healthy Volunteer
NoWhere to participate
Status | Institution | Location |
---|---|---|
Completed | UZ Gent | GENT, 9000, Belgium |
Withdrawn | UZ Brussel | Brussel, 1090, Belgium |
Withdrawn | Universitätsklinikum der Johann Wolfgang Goethe Universität | Frankfurt, 60596, Germany |
Withdrawn | Medizinische Einrichtungen der Universität Bonn | Bonn, 53105, Germany |
Completed | Ciutat Sanitaria i Universitaria de la Vall d'Hebron | Barcelona, 08035, Spain |
Completed | Hospital Universitario 12 de Octubre | Madrid, 28041, Spain |
Completed | Hospital Clínic i Provincial de Barcelona | Barcelona, 08036, Spain |
Withdrawn | Institut Català d'Oncologia Badalona | Badalona, 8916, Spain |
Withdrawn | Krankenhaus Grosshansdorf | Grosshansdorf, 22927, Germany |
Withdrawn | Klinikum der Stadt Köln gGmbH - Krankenhaus Merheim | Köln, 51109, Germany |
Withdrawn | Edith Wolfson Medical Center | Internal Medicine Department | Holon, 5822012, Israel |
Withdrawn | Tel-Aviv Sourasky Medical Center | Tel Aviv, 6423906, Israel |
Withdrawn | Meir Medical Center | Kfar Saba, 4428164, Israel |
Withdrawn | CHU de Liège | LIEGE, 4000, Belgium |
Withdrawn | CHU UCL Namur | Namur, 5000, Belgium |
Withdrawn | Hospital Universitario Clinica Puerta de Hierro | Majadahonda, 28222, Spain |
Withdrawn | Leeds teaching Hospitals | Leeds, WF3 4PX, United Kingdom |
Withdrawn | Wojskowy Instytut Medyczny | Warszawa, 04-141, Poland |
Withdrawn | Uniwersytecki Szpital Kliniczny UM we Wroclawiu | Wroclaw, 50-556, Poland |
Withdrawn | Centrum Onkologii im. Prof. Franciszka Lukaszczyka | Bydgoszcz, 85-796, Poland |
Withdrawn | IRCCS Istituto Europeo di Oncologia s.r.l. (IEO) | Milano, 20141, Italy |
Withdrawn | Fondazione IRCCS Policlinico San Matteo | Pavia, 27100, Italy |
Withdrawn | A.O.U. di Parma | Parma, 43126, Italy |
Withdrawn | Royal Marsden NHS Trust (Surrey) | Sutton, SM2 5PT, United Kingdom |
Withdrawn | Freeman Hospital | Newcastle, NE7 7DN, United Kingdom |
Completed | Ccare San Marcos Cancer Center & Urology | San Marcos, 92069, United States |
Withdrawn | Stony Brook University Medical Center | Stony Brook, 11794, United States |
Withdrawn | UPMC Shadyside | Pittsburgh, 15232-1304, United States |
Withdrawn | Oncology/Hematology Care (OHC) Clinical Trials, LLC | Cincinnati, 45236, United States |
Withdrawn | Levine Cancer Institute | Charlotte, 28204-2990, United States |
Withdrawn | Highlands Oncology Group, PA | Fayetteville, 72703, United States |
Withdrawn | Comprehensive Cancer Centers of Nevada | Las Vegas, 89169, United States |
Withdrawn | Regional Cancer Care Associates, LLC | Somerset, 08873, United States |
Withdrawn | CTCA Southwestern | Tulsa, 74133, United States |
Withdrawn | St. Luke's University Health Network System | Bethlehem, 18015, United States |
Withdrawn | Carilion Clinic | Roanoke, 24014, United States |
Withdrawn | Cancer Treatment Centers of America, Atlanta | Newnan, 30265, United States |
Completed | Nederlands Kanker Instituut | AMSTERDAM, 1066 CX, Netherlands |
Withdrawn | Kindai University Hospital | Osakasayama, 589-8511, Japan |
Withdrawn | National Hospital Organization Kyushu Cancer Center | Fukuoka, 811-1395, Japan |
Withdrawn | Shamir Medical Center (Assaf Harofeh) | Zrifin, 7030000, Israel |
Withdrawn | Clínica Universidad de Navarra CUN | Pamplona, 31008, Spain |
Primary Outcome
- Number of participants with treatment-emergent adverse events in Phase 1A treatment-emergent adverse event (TEAE) was any untoward medical occurrence in a participant, whether or not related to the treatment, arising or worsening after start of study treatment administration until the end of treatment visit (EoT visit, i.e. 30 [+7] days after last dose of study treatment). Severities of the TEAEs are summarized overall and by the maximum grade experienced by the participants for any TEAEs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.5.0.date_rangeTime Frame:Up to 218 days
- Number of participants with treatment-emergent serious adverse events in Phase 1A treatment-emergent serious adverse event (TESAE) was any untoward medical occurrence that resulting in death, initial or prolonged inpatient hospitalization, life-threatening, persistent disability/incapacity, congenital anomaly/birth defect, another medical important serious event as judged by the investigator arising or worsening after start of study treatment administration until 90 days after the cessation of study treatment for serious AE (regardless of causality) or until the end of treatment visit (EoT visit, i.e. 30 [+7] days after last dose of study treatment) visit if the participant initiated new anti-cancer therapy, whichever was earlier.date_rangeTime Frame:Up to 278 days
- Number of participants with dose limiting toxicities (DLTs) in Phase 1Any of following toxicities (exceptions as in protocol) during DLT window was considered a DLT if assessed by investigator to be possibly, probably or definitely related to study treatment: 1.Grade 4 non-hematologic toxicity. 2.Grade 4 hematologic toxicity ≥7 days. 3.Any non-hematologic AE (excl. lab) ≥Grade 3. 4.Any Grade 3 non-hematologic lab value if clinically significant medical intervention required, or the abnormality led to hospitalization, or the abnormality persisted for >1 week. 5.Grade 3 abnormality in AST, ALT, or bilirubin without liver metastases at screening; The abnormality results in a Drug-induced Liver Injury. 6.Febrile neutropenia Grade 3 or 4. 7.Prolonged delay (>2 weeks) in initiating Cycle 2 of pembrolizumab due to treatment-related toxicity 8.Any treatment-related toxicity that caused the participant to discontinue treatment during Cycle 1 or 2. 9.Missing >25% of pembrolizumab doses as a result of drug-related AE(s) during the first cycle. 10.Grade 5 toxicity.date_rangeTime Frame:Within 6 weeks after the first administration of pembrolizumab
- Objective response rate (ORR) per RECIST v1.1 in Phase 2ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) during the course of the study. It was evaluated per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST V1.1). Complete Response (CR): Disappearance of all clinical and radiological evidence of tumor (both target and non-target). Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to < 10mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non target lesions and no appearance of new lesions.date_rangeTime Frame:0 day as Phase 2 never started due to the early termination of the study
Secondary Outcome
- Number of participants categorized by best tumor responses per RECIST v1.1 in Phase 1The tumor responses were evaluated per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST V1.1).date_rangeTime Frame:Up to 188 days
- Objective response rate (ORR) per RECIST v1.1 in Phase 1ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) during the course of the study. It was evaluated per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST V1.1). Complete Response (CR): Disappearance of all clinical and radiological evidence of tumor (both target and non-target). Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to < 10mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non target lesions and no appearance of new lesions. Number of participants with best overall response of CR or PR before early termination of the study is reported in the table below while percentage of participants is auto-calculated by ClinicalTrials.gov database.date_rangeTime Frame:Up to 188 days
- Duration of response (DoR) per RECIST v1.1 in Phase 1DoR was defined as the time interval from the date of first response (CR or PR) to the date of disease progression or death, whichever comes first. It was evaluated per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST V1.1). Complete Response (CR): Disappearance of all clinical and radiological evidence of tumor (both target and non-target). Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to < 10mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non target lesions and no appearance of new lesions.date_rangeTime Frame:Up to 188 days
- Disease control rate (DCR) per RECIST v1.1 in Phase 1DCR was defined as the percentage of participants with CR or PR, or SD for at least 6 weeks during the course of the study. It was evaluated per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST V1.1). Complete Response (CR): Disappearance of all clinical and radiological evidence of tumor (both target and non-target). Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to < 10mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non target lesions and no appearance of new lesions. Stable Disease (SD): Steady state of disease. Number of participants with best overall response of CR or PR or SD is reported below while percentage of participants is auto-calculated by ClinicalTrials.gov database.date_rangeTime Frame:Up to 188 days
- Duration of response (DoR) per RECIST v1.1 in Phase 2DoR was defined as the time interval from the date of first response (CR or PR) to the date of disease progression or death, whichever comes first. It was evaluated per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST V1.1). Complete Response (CR): Disappearance of all clinical and radiological evidence of tumor (both target and non-target). Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to < 10mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non target lesions and no appearance of new lesions.date_rangeTime Frame:0 day as Phase 2 never started due to the early termination of the study
- Disease control rate (DCR) per RECIST v1.1 in Phase 2DCR was defined as the percentage of participants with CR or PR, or SD for at least 6 weeks during the course of the study. It was evaluated per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST V1.1). Complete Response (CR): Disappearance of all clinical and radiological evidence of tumor (both target and non-target). Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to < 10mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non target lesions and no appearance of new lesions. Stable Disease (SD): Steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, no unequivocal progression of existing non target lesions and no appearance of new lesions.date_rangeTime Frame:0 day as Phase 2 never started due to the early termination of the study
- Progression free survival (PFS) per RECIST v1.1 in Phase 2Progression free survival (PFS) was defined as the time from start of any study treatment to the date of earliest radiological progression per RECIST 1.1 or death due to any cause, whichever occurs first. Participants who were alive and without progression at the time of database cut-off would be censored at the date of the last evaluable tumor assessment. RECIST: Response Evaluation Criteria in Solid Tumorsdate_rangeTime Frame:0 day as Phase 2 never started due to the early termination of the study
- Overall survival (OS) in Phase 2Overall survival (OS) was defined as the time from start of any study treatment to the date of death due to any cause. Participants who were alive at the time of database cut-off would be censored at the last date known to be alive or the database cut-off date, whichever occurs first.date_rangeTime Frame:0 day as Phase 2 never started due to the early termination of the study
- Number of participants with treatment-emergent adverse events in Phase 2An treatment-emergent adverse event (TEAE) was any untoward medical occurrence in a participant, whether or not related to the treatment, arising or worsening after start of study treatment administration until the end of treatment visit (EoT visit, i.e. 30 [+7] days after last dose of study treatment). Severities of the TEAEs are summarized overall and by the maximum grade experienced by the participants for any TEAEs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.5.0.date_rangeTime Frame:0 day as Phase 2 never started due to the early termination of the study
- Number of participants with treatment-emergent serious adverse events in Phase 2A treatment-emergent serious adverse event (TESAE) was any untoward medical occurrence that resulting in death, initial or prolonged inpatient hospitalization, life-threatening, persistent disability/incapacity, congenital anomaly/birth defect, another medical important serious event as judged by the investigator arising or worsening after start of study treatment administration until 90 days after the cessation of study treatment for serious AE (regardless of causality) or until the end of treatment visit (EoT visit, i.e. 30 [+7] days after last dose of study treatment) visit if the participant initiated new anti-cancer therapy, whichever was earlier.date_rangeTime Frame:0 day as Phase 2 never started due to the early termination of the study
Trial design
Trial Type
InterventionalIntervention Type
DrugTrial Purpose
TreatmentAllocation
RandomizedBlinding
N/AAssignment
Sequential AssignmentTrial Arms
4