stop_circleTerminated/Withdrawn

Carcinoma, Non-Small-Cell Lung

Bayer Identifier:

19781

ClinicalTrials.gov Identifier:

NCT03996473

EudraCT Number:

2018-003704-39

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

All

Age

18 - N/A
  • - Histologically or cytologically confirmed diagnosis of stage IV NSCLC.
     -- Phase 2 Cohort 1: No Epidermal Growth Factor Receptor (EGFR) / v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutation or anaplastic lymphoma kinase (ALK)/ROS1 rearrangement. Treatment naïve (no prior systemic therapy) for their metastatic NSCLC.
     -- Phase 2 Cohort 2: progression on prior treatment with an immune checkpoint inhibitor inhibitor. Prior treatment with platinum-based chemotherapy in combination or in sequence in line with local standard of care.
     -- Phase 1 includes participants meeting either Cohort 1 or Cohort 2 criteria.
    - Measurable disease per RECIST v1.1.
    - At least 2 skeletal metastases.
    - Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
    - Adequate bone marrow and organ function.
    - Participants must be on a bone health agent (BHA) treatment, such as bisphosphonates or denosumab treatment unless such treatment is contraindicated or not recommended per investigator’s judgement.
  • - Previous or concurrent cancer within 3 years prior to enrollment.
    - Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor. Phase 2 Cohort 2: was discontinued from that treatment due to a Grade 3 or higher immune-related AEs (irAEs).
    - Known active central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
    - Active autoimmune disease that has required systemic treatment in the past 2 years.
    - History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
    - Known history or presence of osteonecrosis of jaw.
    - Ongoing infection >Grade 2 NCI-CTCAE v.5.0 requiring systemic therapy.
    - Significant acute GI disorders with diarrhea as a major symptom e.g., Crohn’s disease, malabsorption, or ≥ NCI-CTCAE v.5.0 Grade 2 diarrhea of any etiology.
    - History of osteoporotic fracture.
    - Prior treatment with radium-223 dichloride or any therapeutic radiopharmaceutical.
    - Prior radiotherapy within 21 days of planned start of study treatment.

Trial summary

Enrollment Goal
8
Trial Dates
March 2020 - January 2023
Phase
Phase 1
Could I Receive a placebo
No
Products
Radium-223 dichloride+pembrolizumab (BAY88-8223)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
UZ GentGENT, 9000, Belgium
Withdrawn
UZ BrusselBrussel, 1090, Belgium
Withdrawn
Universitätsklinikum der Johann Wolfgang Goethe UniversitätFrankfurt, 60596, Germany
Withdrawn
Medizinische Einrichtungen der Universität BonnBonn, 53105, Germany
Completed
Ciutat Sanitaria i Universitaria de la Vall d'HebronBarcelona, 08035, Spain
Completed
Hospital Universitario 12 de OctubreMadrid, 28041, Spain
Completed
Hospital Clínic i Provincial de BarcelonaBarcelona, 08036, Spain
Withdrawn
Institut Català d'Oncologia BadalonaBadalona, 8916, Spain
Withdrawn
Krankenhaus GrosshansdorfGrosshansdorf, 22927, Germany
Withdrawn
Klinikum der Stadt Köln gGmbH - Krankenhaus MerheimKöln, 51109, Germany
Withdrawn
Edith Wolfson Medical Center | Internal Medicine DepartmentHolon, 5822012, Israel
Withdrawn
Tel-Aviv Sourasky Medical CenterTel Aviv, 6423906, Israel
Withdrawn
Meir Medical CenterKfar Saba, 4428164, Israel
Withdrawn
CHU de LiègeLIEGE, 4000, Belgium
Withdrawn
CHU UCL NamurNamur, 5000, Belgium
Withdrawn
Hospital Universitario Clinica Puerta de HierroMajadahonda, 28222, Spain
Withdrawn
Leeds teaching HospitalsLeeds, WF3 4PX, United Kingdom
Withdrawn
Wojskowy Instytut MedycznyWarszawa, 04-141, Poland
Withdrawn
Uniwersytecki Szpital Kliniczny UM we WroclawiuWroclaw, 50-556, Poland
Withdrawn
Centrum Onkologii im. Prof. Franciszka LukaszczykaBydgoszcz, 85-796, Poland
Withdrawn
IRCCS Istituto Europeo di Oncologia s.r.l. (IEO)Milano, 20141, Italy
Withdrawn
Fondazione IRCCS Policlinico San MatteoPavia, 27100, Italy
Withdrawn
A.O.U. di ParmaParma, 43126, Italy
Withdrawn
Royal Marsden NHS Trust (Surrey)Sutton, SM2 5PT, United Kingdom
Withdrawn
Freeman HospitalNewcastle, NE7 7DN, United Kingdom
Completed
Ccare San Marcos Cancer Center & UrologySan Marcos, 92069, United States
Withdrawn
Stony Brook University Medical CenterStony Brook, 11794, United States
Withdrawn
UPMC ShadysidePittsburgh, 15232-1304, United States
Withdrawn
Oncology/Hematology Care (OHC) Clinical Trials, LLCCincinnati, 45236, United States
Withdrawn
Levine Cancer InstituteCharlotte, 28204-2990, United States
Withdrawn
Highlands Oncology Group, PAFayetteville, 72703, United States
Withdrawn
Comprehensive Cancer Centers of NevadaLas Vegas, 89169, United States
Withdrawn
Regional Cancer Care Associates, LLCSomerset, 08873, United States
Withdrawn
CTCA SouthwesternTulsa, 74133, United States
Withdrawn
St. Luke's University Health Network SystemBethlehem, 18015, United States
Withdrawn
Carilion ClinicRoanoke, 24014, United States
Withdrawn
Cancer Treatment Centers of America, AtlantaNewnan, 30265, United States
Completed
Nederlands Kanker InstituutAMSTERDAM, 1066 CX, Netherlands
Withdrawn
Kindai University HospitalOsakasayama, 589-8511, Japan
Withdrawn
National Hospital Organization Kyushu Cancer CenterFukuoka, 811-1395, Japan
Withdrawn
Shamir Medical Center (Assaf Harofeh)Zrifin, 7030000, Israel
Withdrawn
Clínica Universidad de Navarra CUNPamplona, 31008, Spain

Primary Outcome

  • Number of participants with treatment-emergent adverse events in Phase 1
    A 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 1
    A 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 1
    Any 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 2
    ORR 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 1
    The 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 1
    ORR 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 1
    DoR 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 1
    DCR 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 2
    DoR 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 2
    DCR 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 2
    Progression 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 Tumors
    date_rangeTime Frame:
    0 day as Phase 2 never started due to the early termination of the study
  • Overall survival (OS) in Phase 2
    Overall 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 2
    An 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 2
    A 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

An open-label, multicenter, Phase 1/2 study of radium-223 dichloride in combination with pembrolizumab in participants with stage IV non-small cell lung cancer
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Randomized
Blinding
N/A
Assignment
Sequential Assignment
Trial Arms
4

Additional Information

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