Trilaciclib (G1T28) in Patients With Previously Treated Extensive Stage SCLC Receiving Topotecan Chemotherapy
- Conditions
- Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT02514447
- Lead Sponsor
- G1 Therapeutics, Inc.
- Brief Summary
This was a study to investigate the potential clinical benefit of trilaciclib (G1T28), a Cyclin Dependent Kinase (CDK) 4/6 inhibitor, in preserving the bone marrow and the immune system, in order to decrease chemotherapy-induced myelosuppression and improve anti-tumor efficacy when administered prior to topotecan in patients previously treated for extensive-stage SCLC.
The study consisted of 2 parts: a limited open-label, dose-finding portion (Part 1), and a randomized double-blind portion (Part 2). Both parts included 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase began on the day of first dose with study treatment and completes at the Post-Treatment Visit.
- Detailed Description
Overall, up to 130 patients were planned to be enrolled in the study. In Part 1, approximately 40 patients were planned to be enrolled, assuming 9 to 10 cohorts. Part 1 was open-label, and no randomization or blinding was required. In Part 2A, approximately 45 patients were to be enrolled and randomly assigned (2:1) to trilaciclib (240 mg/m2) and topotecan (0.75 mg/m2) or placebo and topotecan (1.5 mg/m2). In Part 2B, approximately 45 patients were to be enrolled and randomly assigned (2:1) to trilaciclib (240 mg/mg2) and topotecan (1.5 mg/m2) or placebo and topotecan (1.5 mg/m2).
Patients who received placebo in Part 2A and Part 2B were to be combined into a single placebo group for the analysis to compare with trilaciclib+topotecan 1.5 mg/m2 with placebo + topotecan 1.5 mg/m2 (proximately 30 per treatment group).
The sample size calculation was to demonstrate the superiority of trilaciclib + topotecan 1.5 mg/m2 over placebo + topotecan 1.5 mg/m2 with respect to at least 1 of the primary endpoints. The overall type I error rate was 1-sided 0.10. Using the most conservative Bonferroni procedure for the 2 primary endpoints, a 1-sided individual type I error rate 0.10/2=0.05 was assigned to each outcome variable (DSN in Cycle 1 and occurrence of SN) in the sample size calculation. Assuming a common standard deviation of 2.5, a difference in the duration of SN in Cycle 1 of at least 2 days between the treatment groups, a sample size of 28 per arm was required to have 90% power to detect the assumed treatment effect. For occurrence of SN, assuming the event rate was 45% for placebo group, to detect an absolute reduction of 37% by trilaciclib group with 90% power would require a sample size of at least 29 per arm. Thus, 30 per arm was needed to ensure 90% power to detect assumed treatment effect for DSN in Cycle 1 and occurrence of SN. All calculations were carried out using the POWER procedure in SAS®, Version 9.4 procedure in SAS®, Version 9.4 or higher.
The results from endpoints that were commonly collected at Part 1 and part 2 are presented together in this report.
The posted results represent the final results of Study G1T28-03, a Phase 1b/2a safety and pharmacokinetic (PK) study of trilaciclib (G1T28) in patients with previously treated extensive-stage small cell lung cancer (SCLC) receiving topotecan chemotherapy in the second/third-line (2/3L) setting. The final myelopreservation efficacy results for both parts and exposure for Part 1 are from database lock 1 (data cut-off \[DCO\] for Primary Completion Date \[PCD\] 28 September 2018). The final anti-tumor efficacy (BOR, DOR, PFS) for both parts, final overall survival for Part 1 and exposure data from Part 2 are from a second database lock 2 (DCO 31 May 2019) and the final overall survival for Part 2 and safety (adverse events) are through the end of the study on October 4, 2021 which resulted in the final database lock (DCO 01 Nov 2021).
The maximum time frames provided reflect the time from when the first patient could be evaluated for an endpoint (ie. date of first dose of first patient) to the time when the data from both parts presented for that endpoint was considered final.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 123
- Male or female subjects aged ≥18 years
- Confirmed diagnosis of SCLC by histology or cytology, preferably including the presence of neuroendocrine features by immunohistochemistry
- Progression during or after prior first- or second-line chemotherapy and eligible to receive topotecan therapy
- At least 1 target lesion that is measurable by RECIST, Version 1.1
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
- Adequate organ function
Key
- Presence of brain metastases requiring immediate treatment with radiation therapy or steroids.
- Uncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failure
- Known history of stroke or cerebrovascular accident within 6 months prior to enrollment
- Other uncontrolled serious chronic disease or conditions that in the investigator's opinion could affect compliance or follow-up in the protocol
- Concurrent radiotherapy to any site or radiotherapy within 2 weeks prior to enrollment or previous radiotherapy to the target lesion sites
- Receipt of any systemic chemotherapy regimen within 4 weeks prior to enrollment or a noncytotoxic investigational medication within 2 weeks prior to enrollment
- History of topotecan treatment for SCLC
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Placebo Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Trilaciclib Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Placebo + Topotecan 1.5 mg/m² - Parts 2a and 2b Topotecan Patients in Parts 2a and 2b were randomized 1:2 to placebo. Patients received placebo administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of placebo on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Part 2a Topotecan Patients in Part 2a were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Trilaciclib Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Trilaciclib Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.5 mg/m² - Part 2b Topotecan Patients in Part 2b were randomized 2:1 to trilaciclib. Patients received trilaciclib (240 mg/m²) administered IV once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.5 mg/m²). Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Trilaciclib Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Trilaciclib Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.5 mg/m² - Cohort 1- Part 1 Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.50 mg/m²). Trilaciclib (G1T28) 200 mg/m² + Topotecan 1.25 mg/m² - Cohort 2- Part 1 Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.25 mg/m²). Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Trilaciclib Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Topotecan Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib (G1T28) 280 mg/m² + Topotecan 0.75 mg/m² - Cohort 5- Part 1 Topotecan Patients received trilaciclib (280 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib (G1T28) 200 mg/m² + Topotecan 0.75 mg/m² - Cohort 3- Part 1 Topotecan Patients received trilaciclib (200 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib (G1T28) 240 mg/m² + Topotecan 0.75 mg/m² - Cohorts 4 and 6- Part 1 Trilaciclib Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (0.75 mg/m²). Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 Trilaciclib Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²). Trilaciclib (G1T28) 240 mg/m² + Topotecan 1.0 mg/m² - Cohort 7- Part 1 Topotecan Patients received trilaciclib (240 mg/m²) administered intravenously (IV) once daily on Days 1 to 5 of each 21-day topotecan chemotherapy cycle. Following administration of trilaciclib on Days 1 to 5, patients received IV topotecan (1.0 mg/m²).
- Primary Outcome Measures
Name Time Method Duration of Severe (Grade 4) Neutropenia in Cycle 1 Evaluated for Cycle 1 (i.e., from date of first dose of study drug (Part 1)/randomization (Part 2) to the end of Cycle 1, each cycle = 21 days) Duration of severe neutropenia (DSN; days) was defined as the number of days from the date of the first ANC value of \<0.5 × 10\^9/L observed between start of cycle and end of cycle to the date of the first ANC value ≥0.5 × 10\^9/L that met the following criteria: (1) occurred after the ANC value of \<0.5 × 10\^9/L and (2) no other ANC values \<0.5 × 10\^9/L occurred between this day and end of cycle. DSN is set to 0 for patients who did not experience SN in a cycle, including those who were randomized but never treated. Data from unscheduled visits and the actual assessment date (rather than visit date) were included in the derivation.
Occurrence of Severe (Grade 4) Neutropenia During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). Number of Participants with severe (Grade 4) neutropenia (SN) was a binary variable. If a patient had at least 1 absolute neutrophil count value \<0.5 × 10\^9/L during the Treatment Period, the patient was assigned as Yes to the occurrence of SN; otherwise, it was No.
Assess the Dose Limiting Toxicities (DLTs) of G1T28/Trilaciclib Administered With Topotecan in Part 1 Evaluated for Cycle 1 (i.e., from date of first dose of study drug (Part 1) to the end of Cycle 1, each cycle = 21 days) The percentage of patients experiencing DLTs in Part 1 of the study in each cohort, including:
* Absolute neutrophil count (ANC) \< 0.5 × 10\^9/L lasting for ≥ 7 days
* ≥ Grade 3 neutropenic infection/febrile neutropenia
* Grade 4 thrombocytopenia or ≥ Grade 3 thrombocytopenia with bleeding
* Unable to start next cycle of chemotherapy due to lack of recovery to an ANC ≥ 1.5 × 10\^9/L and platelet count ≥ 100 × 10\^9/L; a delay of up to 1 week from the scheduled start of Cycle 2 is allowed for recovery of ANC and platelet count, and is not considered a DLT
* ≥ Grade 3 nonhematologic toxicity (nausea, vomiting, and diarrhea failing maximal medical management; fatigue lasting for \> 72 hours)
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) From date of first dose of study drug (Part 1)/randomization (Part 2) until the occurrence of progressive disease, withdrawal of consent, or initiation of subsequent anti-cancer therapy, (assessed up to a maximum of 1335 days). The median months and 95% CIs of duration of response.
Pharmacokinetic Profile for Trilaciclib (G1T28) When Administered With Topotecan Part 1 of the study during Cycle 1 Day 4 : predose, 0.5, 1, 1.5, 2, 2.5, 3, 4.5, 6.5, 8.5 (optional), and 24.5 hours post dose. Part 2 of the study during Cycle 1 Day 4 : predose, 0.5, 1, between 3 to 4 hours and between 5.5 to 6.5 hours post dose. Maximum concentration (Cmax) of trilaciclib (G1T28) when administered with topotecan
Occurrence of RBC Transfusions During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1056 days). Percentage of patients requiring a RBC transfusion on/after week 5
Progression Free Survival (PFS) From date of first dose of study drug (Part 1)/randomization (Part 2), until date of documented disease progression or death due to any cause (evaluated up to a maximum of 1335 days). Median time (months) and 95% CI from date of first dose of study drug/randomization until date of documented disease progression or death due to any cause.
Investigators followed the Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 guidelines for tumor assessments to determine progression. Progressive Disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).Overall Survival (OS) From date of first dose of study drug (Part 1)/randomization (Part 2) until the date of death due to any cause (evaluated up to a maximum of 2220 days). Median time (months) and 95% CI from date of first dose date of study drug/randomization until date of death. Patients who do not die during the study will be censored at the date last known to be alive.
Pharmacokinetic Profile for Topotecan When Administered With Trilaciclib (G1T28) Part 1 of the study during Cycle 1 Day 4 : predose, 0.5, 1, 1.5, 2, 2.5, 3, 4.5, 6.5, 8.5 (optional), and 24.5 hours post dose. Part 2 of the study during Cycle 1 Day 4 : predose, 0.5, 1, between 3 to 4 hours and between 5.5 to 6.5 hours post dose. Maximum concentration (Cmax) of topotecan when administered with trilaciclib (G1T28)
Occurrence of Intravenous (IV) Antibiotic Use During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). Percentage of patients requiring systemic/IV antibiotics
Occurrence of Pulmonary Infection Serious Adverse Events (SAEs) During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). Percentage of patients experiencing an SAE that codes to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) of Infections and Infestations and falls into a preferred term (PT) categorized as a pulmonary infection custom MedDRA query (CMQ)
Occurrence of Grade 4 and Grade 3/4 Decreased Platelet Count Laboratory Values (Thrombocytopenia) During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). The count of patients with any platelet lab value that meets the CTCAE toxicity grade criteria for ≥ Grade 3 and the value is treatment emergent (occurs after first dose of study drug).
Occurrence of Erythropoietin-stimulating Agent (ESA) Administrations During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). The count of patients who received any ESA administration.
Chemotherapy Exposure During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to a maximum of 1335 days). Average duration of exposure to chemotherapy (topotecan) in days.
Assess the Hematologic Profile of G1T28/Trilaciclib Administered With Topotecan During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). The weekly event rate of Major Adverse Hematologic Events (MAHE) events
Occurrence of Platelet Transfusions During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). Percentage of patients requiring a platelet transfusion
Occurrence of Infection Serious Adverse Events (SAEs) During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). Percentage of patients experiencing an SAE that codes to the Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) of Infections and Infestations
Occurrence of Grade 3 and 4 Hematologic Toxicities During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). The count of patients with any hematologic lab value that meets the CTCAE toxicity grade criteria for ≥ Grade 3 and the value is treatment emergent (occurs after first dose of study drug). Labs include: Hemoglobin (HGB), hematocrit, white blood cell (WBC), platelet counts, ANC, ALC, Monocyte Absolute, Basophil Absolute, and Eosinophil Absolute.
Tumor Response Based on RECIST, Version 1.1 From date of first dose of study drug (Part 1)/randomization (Part 2) until the occurrence of progressive disease, withdrawal of consent, or initiation of subsequent anti-cancer therapy, (assessed up to a maximum of 1335 days). The percentage of patients who fall into each category of Best overall response (BOR) as defined by RECIST, Version 1.1.
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.
Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions.
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
When no imaging/measurement is done, the patient is not evaluable (NE); and if only a subset of lesion measurements are made, usually the case is also considered NE.Chemotherapy Cycles and Modifications Overall During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to a maximum of 1335 days). Average exposure and cycle modifications in chemotherapy (topotecan)
Dose Reductions in Chemotherapy (Topotecan) During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). Overall event rate of dose reductions in chemotherapy (topotecan)
Need for Treatment With Hematopoietic Growth Factors During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). Percentage of patients requiring G-CSF administration.
Occurrence of Febrile Neutropenia Adverse Events During the treatment period. From date of first dose (Part 1)/randomization (Part 2), 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator (assessed up to 1090 days). Percentage of patients who experience febrile neutropenia adverse events
Trial Locations
- Locations (50)
Genesis Cancer Center
🇺🇸Hot Springs, Arkansas, United States
Highlands Oncology Group
🇺🇸Rogers, Arkansas, United States
Greenville Health System
🇺🇸Greenville, South Carolina, United States
AnMed Health
🇺🇸Anderson, South Carolina, United States
University Clinic of Respiratory and Allergic Diseases Golnik
🇸🇮Golnik, Slovenia
Gibbs Cancer Center
🇺🇸Spartanburg, South Carolina, United States
VOU Department of Radiotherapy and Oncology
🇸🇰Kosice, Slovakia
Texas Oncology- Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
M.D. Anderson
🇺🇸Houston, Texas, United States
Florida Cancer Specialists - South
🇺🇸Fort Myers, Florida, United States
Northside Hospital - Georgia Cancer Specialists
🇺🇸Atlanta, Georgia, United States
The University of Texas Health Science Center at Tyler
🇺🇸Tyler, Texas, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Millennium Oncology
🇺🇸Houston, Texas, United States
Clinical Hospital Centre Osijek
🇭🇷Osijek, Croatia
Sutter Medical Group
🇺🇸Sacramento, California, United States
Compassionate Cancer Care Medical Group, Inc.
🇺🇸Corona, California, United States
The Oncology Institute of Hope and Innovation
🇺🇸Whittier, California, United States
Memorial Hospital - University of Colorado Health
🇺🇸Colorado Springs, Colorado, United States
University of Colorado Health, Oncology Clinical Research Northern Region
🇺🇸Fort Collins, Colorado, United States
Florida Cancer Specialists - North
🇺🇸Tavares, Florida, United States
Emory University
🇺🇸Atlanta, Georgia, United States
University Cancer and Blood Center, LLC
🇺🇸Athens, Georgia, United States
Saint Luke's Cancer Institute
🇺🇸Kansas City, Missouri, United States
Norris Cotton Cancer Center
🇺🇸Lebanon, New Hampshire, United States
Regional Medical Oncology Center
🇺🇸Wilson, North Carolina, United States
North Shore Hematology Oncology Associates PC
🇺🇸East Setauket, New York, United States
Guthrie Medical Group, PC
🇺🇸Sayre, Pennsylvania, United States
Hanna Cancer Associates - University of Tennessee
🇺🇸Knoxville, Tennessee, United States
Southwest Cancer Center
🇺🇸Lubbock, Texas, United States
Texas Oncology
🇺🇸Tyler, Texas, United States
AZ Klina
🇧🇪Brasschaat, Belgium
University Clinical Centre Banja Luka
🇧🇦Banja Luka, Bosnia and Herzegovina
University Clinical Centre Sarajevo
🇧🇦Sarajevo, Bosnia and Herzegovina
Northwest Cancer Specialists, P.C.
🇺🇸Vancouver, Washington, United States
University Clinical Hospital Centre " Sestre Milosrdnice"
🇭🇷Zagreb, Croatia
University Hospital Centre Zagreb, Clinic For Pulmonary Diseases Jordanovac
🇭🇷Zagreb, Croatia
University Clinic of Radiotherapy and Oncology Skopje
🇲🇰Skopje, North Macedonia
Clinic for Pulmology, Clinical Centre of Serbia
🇷🇸Belgrade, Serbia
Oncology and Radiology Institute of Serbia
🇷🇸Belgrade, Serbia
Clinical Hospital Centre Bezanijska Kosa
🇷🇸Belgrade, Serbia
Clinical Center Nis, Clinic for Lung Diseases
🇷🇸Nis, Serbia
Institute for Pulmonary Diseases of Vojvodina Clinic for Thoracic Oncology
🇷🇸Sremska Kamenica, Serbia
POKO POPRAD, s.r.o.
🇸🇰Poprad, Slovakia
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Oklahoma University - Peggy and Charles Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Meharry Medical College
🇺🇸Nashville, Tennessee, United States
Rocky Mountain Cancer Centers
🇺🇸Denver, Colorado, United States
Gabrail Cancer Center
🇺🇸Canton, Ohio, United States