Carboplatin, Etoposide, and Atezolizumab With or Without Trilaciclib (G1T28), a CDK4/6 Inhibitor, in Extensive-Stage SCLC
- Conditions
- Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT03041311
- Lead Sponsor
- G1 Therapeutics, Inc.
- Brief Summary
This was a study to investigate the potential clinical benefit of trilaciclib (G1T28) in preserving the bone marrow and the immune system, and enhancing antitumor efficacy when administered with carboplatin, etoposide, and atezolizumab (E/P/A) therapy in first line treatment for patients with newly diagnosed extensive-stage SCLC.
The study was a randomized, double-blinded, placebo-controlled design. Approximately, 100 patients were randomized to trilaciclib + E/P/A or placebo + E/P/A in the study.
- Detailed Description
The posted results represent the final results from Study G1T28-05, a Phase 2 study of carboplatin, etoposide, and atezolizumab with or without trilaciclib (G1T28) in patients with untreated extensive-stage small cell lung cancer (SCLC).
The final myelopreservation efficacy results are from database lock 1 (data cut-off \[DCO\] 17 Aug 2018). The final anti-tumor efficacy data (BOR, DOR, PFS) are from a second database lock 2 (DCO 28 June 2019) that occurred to support the trilaciclib New Drug Application (NDA). Final overall survival and safety data are reported from the final study database lock (DCO 11 Dec 2020, last patient last visit date of 29 October 2020).
Please note the last patient last visit date description above which is recorded as the study completion date. Following the last patient last visit, the final database lock occurred a few weeks later which accounts for the discrepancy between the study completion date and the reported assessment time frames.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 107
- Male or female subjects aged ≥18 years
- Unequivocally confirmed diagnosis of SCLC by histology or cytology, preferably including the presence of neuroendocrine features by immunohistochemistry
- Extensive-stage SCLC
- At least 1 target lesion that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
- Adequate organ function
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
- Predicted life expectancy of ≥3 months
- Able to understand and sign an informed consent
- Limited-stage SCLC
- Prior chemotherapy for limited or extensive-stage SCLC
- Prior treatment with immunotherapies including but not limited to cluster of differentiation 137 agonists or immune checkpoint blockade therapies (such as anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1(PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) therapeutic antibodies).
- Presence of symptomatic brain metastases requiring immediate treatment with radiation therapy or steroids.
- Malignancies other than SCLC within 3 years prior to randomization, with the exception of those with negligible risk of metastasis or death treated with expected curative outcome
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
- Active, known, suspected autoimmune disease requiring systemic treatment in the past 2 years
- Uncontrolled ischemic heart disease or uncontrolled symptomatic congestive heart failure
- Known history of stroke or cerebrovascular accident within 6 months prior to enrollment
- Serious active infection at the time of enrollment
- Psychiatric illness/social situations that would limit study compliance
- Other uncontrolled serious chronic disease or conditions that in the investigator's opinion could affect compliance or follow-up in the protocol
- Known human immunodeficiency virus, known active hepatitis B, or hepatitis C
- Radiotherapy to any site or radiotherapy within 2 weeks prior to enrollment
- Receipt of any investigational medication within 4 weeks prior to enrollment
- Administration of attenuated vaccine within 4 weeks before enrollment or anticipation that such a live attenuated vaccine will be required during the study
- Influenza vaccination should be given during influenza season only (approx. Oct to March). Patients must not receive live, attenuated influenza vaccine (eg, FluMist) within 4 weeks prior to enrollment at any time during the study, and at least 5 months after the last dose of atezolizumab.
- Patients with a condition requiring systemic treatment with either corticosteroids ( > 10 mg daily prednisone equivalents) or other immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 14 days of study drug administration. Inhaled or topical steroids ad adrenal replacement dosed > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- Hypersensitivity to any of the components of the formulation of etoposide or etoposide phosphate
- Hypersensitivity to carboplatin or other platinum-containing compounds or to mannitol
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
- Legal incapacity or limited legal capacity
- Pregnant or lactating women
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description placebo+etoposide/carboplatin/atezolizumab Placebo Induction: Patients received placebo administered IV once daily prior to E/P/A on Days 1, 2 and 3 of each 21-day E/P/A therapy cycle (up to 4 cycles in total). Etoposide 100 mg/m² was administered IV daily on Days 1, 2, and 3 of each 21-day cycle. Carboplatin was be administered on Day 1 of each 21-day cycle using the Calvert formula with a target AUC = 5 mg/mL/min to calculate the dose. Atezolizumab 1200 mg was administered as an IV infusion on Day 1 of each 21-day cycle. Maintenance: Following the induction phase, patients received maintenance atezolizumab at a dose of 1200 mg on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or discontinuation by the patient or investigator. trilaciclib+etoposide/carboplatin/atezolizumab Carboplatin Induction: Patients received trilaciclib 240 mg/m² administered intravenously (IV) once daily prior to E/P/A on Days 1, 2 and 3 of each 21-day E/P/A therapy cycle (up to 4 cycles in total). Etoposide 100 mg/m² was administered IV daily on Days 1, 2, and 3 of each 21-day cycle. Carboplatin was administered on Day 1 of each 21-day cycle using the Calvert formula with a target area under the concentration-time curve (AUC) = 5 milligrams per milliliter per minute (mg/mL/min) to calculate the dose. Atezolizumab 1200 mg was administered as an IV infusion on Day 1 of each 21-day cycle. Maintenance: Following the induction phase, patients received maintenance atezolizumab at a dose of 1200 mg on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or discontinuation by the patient or investigator. trilaciclib+etoposide/carboplatin/atezolizumab Trilaciclib Induction: Patients received trilaciclib 240 mg/m² administered intravenously (IV) once daily prior to E/P/A on Days 1, 2 and 3 of each 21-day E/P/A therapy cycle (up to 4 cycles in total). Etoposide 100 mg/m² was administered IV daily on Days 1, 2, and 3 of each 21-day cycle. Carboplatin was administered on Day 1 of each 21-day cycle using the Calvert formula with a target area under the concentration-time curve (AUC) = 5 milligrams per milliliter per minute (mg/mL/min) to calculate the dose. Atezolizumab 1200 mg was administered as an IV infusion on Day 1 of each 21-day cycle. Maintenance: Following the induction phase, patients received maintenance atezolizumab at a dose of 1200 mg on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or discontinuation by the patient or investigator. trilaciclib+etoposide/carboplatin/atezolizumab Etoposide Induction: Patients received trilaciclib 240 mg/m² administered intravenously (IV) once daily prior to E/P/A on Days 1, 2 and 3 of each 21-day E/P/A therapy cycle (up to 4 cycles in total). Etoposide 100 mg/m² was administered IV daily on Days 1, 2, and 3 of each 21-day cycle. Carboplatin was administered on Day 1 of each 21-day cycle using the Calvert formula with a target area under the concentration-time curve (AUC) = 5 milligrams per milliliter per minute (mg/mL/min) to calculate the dose. Atezolizumab 1200 mg was administered as an IV infusion on Day 1 of each 21-day cycle. Maintenance: Following the induction phase, patients received maintenance atezolizumab at a dose of 1200 mg on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or discontinuation by the patient or investigator. trilaciclib+etoposide/carboplatin/atezolizumab Atezolizumab Induction: Patients received trilaciclib 240 mg/m² administered intravenously (IV) once daily prior to E/P/A on Days 1, 2 and 3 of each 21-day E/P/A therapy cycle (up to 4 cycles in total). Etoposide 100 mg/m² was administered IV daily on Days 1, 2, and 3 of each 21-day cycle. Carboplatin was administered on Day 1 of each 21-day cycle using the Calvert formula with a target area under the concentration-time curve (AUC) = 5 milligrams per milliliter per minute (mg/mL/min) to calculate the dose. Atezolizumab 1200 mg was administered as an IV infusion on Day 1 of each 21-day cycle. Maintenance: Following the induction phase, patients received maintenance atezolizumab at a dose of 1200 mg on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or discontinuation by the patient or investigator. placebo+etoposide/carboplatin/atezolizumab Carboplatin Induction: Patients received placebo administered IV once daily prior to E/P/A on Days 1, 2 and 3 of each 21-day E/P/A therapy cycle (up to 4 cycles in total). Etoposide 100 mg/m² was administered IV daily on Days 1, 2, and 3 of each 21-day cycle. Carboplatin was be administered on Day 1 of each 21-day cycle using the Calvert formula with a target AUC = 5 mg/mL/min to calculate the dose. Atezolizumab 1200 mg was administered as an IV infusion on Day 1 of each 21-day cycle. Maintenance: Following the induction phase, patients received maintenance atezolizumab at a dose of 1200 mg on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or discontinuation by the patient or investigator. placebo+etoposide/carboplatin/atezolizumab Etoposide Induction: Patients received placebo administered IV once daily prior to E/P/A on Days 1, 2 and 3 of each 21-day E/P/A therapy cycle (up to 4 cycles in total). Etoposide 100 mg/m² was administered IV daily on Days 1, 2, and 3 of each 21-day cycle. Carboplatin was be administered on Day 1 of each 21-day cycle using the Calvert formula with a target AUC = 5 mg/mL/min to calculate the dose. Atezolizumab 1200 mg was administered as an IV infusion on Day 1 of each 21-day cycle. Maintenance: Following the induction phase, patients received maintenance atezolizumab at a dose of 1200 mg on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or discontinuation by the patient or investigator. placebo+etoposide/carboplatin/atezolizumab Atezolizumab Induction: Patients received placebo administered IV once daily prior to E/P/A on Days 1, 2 and 3 of each 21-day E/P/A therapy cycle (up to 4 cycles in total). Etoposide 100 mg/m² was administered IV daily on Days 1, 2, and 3 of each 21-day cycle. Carboplatin was be administered on Day 1 of each 21-day cycle using the Calvert formula with a target AUC = 5 mg/mL/min to calculate the dose. Atezolizumab 1200 mg was administered as an IV infusion on Day 1 of each 21-day cycle. Maintenance: Following the induction phase, patients received maintenance atezolizumab at a dose of 1200 mg on Day 1 of every 21-day cycle until disease progression, unacceptable toxicity or discontinuation by the patient or investigator.
- Primary Outcome Measures
Name Time Method Duration of Severe (Grade 4) Neutropenia in Cycle 1 Evaluated for Cycle 1 of the Induction Period (i.e., from randomization 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 absolute neutrophil count (ANC) value of \<0.5 × 10⁹/L observed between start of cycle and end of cycle to the date of the first ANC value ≥0.5 × 10⁹/L that met the following criteria: (1) occurred after the ANC value of \<0.5 × 10⁹/L and (2) no other ANC values \<0.5 × 10⁹/L occurred between this day and end of cycle. DSN was set to 0 for patients who did not experience severe neutropenia in a cycle, including those that were randomized and not treated. Data from unscheduled visits and the actual assessment date (rather than visit date) were included in the derivation.
Number of Participants With at Least 1 Occurrence of Severe (Grade 4) Neutropenia Induction Period. From date of randomization, 21 day treatment cycles up to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days. The occurrence of 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 Induction Period, the patient was assigned as Yes to the occurrence of SN; otherwise, it was No.
- Secondary Outcome Measures
Name Time Method Duration of Objective Response (Complete Response or Partial Response) From date of randomization, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 724 days. Duration of Response (DOR) is the time between first response by RECIST Version 1.1 of CR or PR and the first date that progressive disease is documented by RECIST Version 1.1, or death. Patients who do not experience PD or death will be censored at the last tumor assessment date. Only those patients with confirmed responses will be included in this analysis.
Number of Participants With at Least 1 Occurrence of Erythropoiesis Stimulating Agent (ESA) Administration Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days. Any ESA administration in a cycle during the Induction Period was defined as a separate event. A patient with at least 1 cycle with ESA administration during an induction cycle or the Induction Period was considered to have occurrence of ESA administration. The criterion to select proper records was as follows: If the chemical subgroup from WHO-DD Version September 2017 (ie TEXT4 for CODE4) takes the value "OTHER ANTIANEMIC PREPARATIONS," the medication was classified as ESAs.
Number of Participants With at Least 1 Occurrence of Pulmonary Infection Serious Adverse Events (SAEs) Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days. Any occurrence of a pulmonary SAE during the induction treatment period was defined as a binary variable (Yes or No); Yes if total number of febrile neutropenia events ≥ 1 is observed, No for other scenarios. If the patient did not have an event, the value of 0 was assigned to that patient. Each pulmonary infection SAE with a unique start date during the induction treatment period was defined as separate event. The criterion for identifying the proper pulmonary infection SAE records was as follows:
The SOC from MedDRA Version 20.1 took the value "INFECTIONS AND INFESTATIONS," the adverse event was a serious event, and the PT took values from the following list of PTs under the category of pulmonary infection adverse events: bronchiolitis, bronchitis, infectious pleural effusion, influenza, pneumonia, pneumonia bacterial, respiratory tract infection, upper respiratory tract infection, and viral upper respiratory tract infection.All-Cause Dose Reductions Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days. Dose reductions are not permitted for trilaciclib or atezolizumab. Dose reductions for E/P are derived from changes in the protocol-specified dose on the dosing page and correspond to the reductions for toxicity specified in the protocol. No more than 2 dose reductions of E/P in total were allowed for any patient. Simultaneous reduction in the doses of etoposide and carboplatin were counted as 1 dose reduction.
Major Adverse Hematologic Events (MAHE) (Composite Endpoint) Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days. The composite endpoint "major adverse hematologic events" (MAHE) included the following aspects of myelosuppression:
All-cause hospitalizations - Each recorded preferred term (PT) with a unique start date was counted as an event.
All-cause dose reductions - Dose reductions were permitted for E/P but not for trilaciclib or atezolizumab. No more than 2 dose reductions were allowed. Each dose reduction was counted as a separate event.
Febrile neutropenia-Each febrile neutropenia event with a unique start date during the Induction Period was defined as a separate event.
Prolonged severe neutropenia (SN)-Each cycle with a severe neutropenia duration greater than 5 days was counted as an event, with the date of the first Grade 4 laboratory value defined as the start date for the time-to-first event analysis.
Red blood cell (RBC) transfusion on/after Week 5-Each RBC transfusion with a unique start date on/after Week 5 on study during the Induction Period was defined as a separate event.Number of Participants With at Least 1 Occurrence of Febrile Neutropenia Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days. The criterion for identifying febrile neutropenia was if the preferred term for an adverse event was "FEBRILE NEUTROPENIA." Any occurrence of a febrile neutropenia event during the induction treatment period is defined as a binary variable (Yes or No); Yes if total number of febrile neutropenia events ≥ 1 is observed, No for other scenarios. Each febrile neutropenia event with a unique start date during the induction treatment period was defined as a separate event.
Occurrence of Granulocyte Colony-Stimulating Factor (G-CSF) Administration (Proportion of Patients) Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days. For this endpoint, the occurrence during the Induction Period was defined as a binary variable (Yes or No); Yes, if total number of events ≥1 was observed, No for other scenarios. If a patient did not have an event, a value of 0 was assigned to that patient. Any G-CSF administration in a cycle during the Induction Period was defined as a separate event. A patient with at least 1 cycle with G-CSF administration during an induction cycle or the Induction Period was considered to have occurrence of G-CSF administration.
Best Overall Response From date of randomization, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 724 days. For all patients, the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) tumor response data were used to determine each patient's visit response (TPR = time point response). Per RECIST v1.1 for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameters of target lesions; Progressive Disease (PD), \>=20% increase in the sum of the longest diameter of target lesions, Stable Disease, neither sufficient shrinkage or increase to quality for PR or PD. Objective Response Rate (ORR) = CR + PR. The TPR at each visit was determined in 2 ways: (1) derived programmatically at the time of analysis using the information from target lesions, non-target lesions, and new lesions based on data collected through eCRF; and (2) judged by the investigator as collected in the eCRF. Results shown here are from the programmatically derived assessments.
Number of Participants With at Least 1 Occurrence of RBC Transfusion on/After Week 5 (Proportion of Patients) Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 374 days. For this endpoint, the occurrence during the Induction Period was defined as a binary variable (Yes or No); Yes, if total number of events ≥1 was observed, No for other scenarios. If a patient did not have an event, a value of 0 was assigned to that patient. Each red blood cell transfusion with a unique start date on/after Week 5 on study during the Induction was defined as a separate event.
Progression-Free Survival From date of randomization, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 724 days. Progression-free survival (PFS) was defined as the time (number of months) from date of randomization until date of documented radiologic disease progression per RECIST v1.1 or death due to any cause, whichever came first.
Overall Survival (OS) From date of randomization to date of death due to any cause, assessed up to a maximum of 38.1 months. Overall survival was calculated as the time (months) from date of randomization to the date of death due to any cause. Patients who did not die during the study were censored at the date last known to be alive. Patients lacking data beyond the date of randomization had their survival time censored at date of randomization. Overall survival was not censored if a patient received other anti-tumor treatments after the study drugs. Overall survival was calculated using the Kaplan-Meier method.
Number of Participants With at Least 1 Occurrence of Grade 3 or 4 Hematologic Laboratory Abnormalities Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days. The occurrence of Grade 3 and 4 hematologic toxicities was a binary endpoint. If a patient had at least 1 cycle with at least 1 Grade 3 or 4 hematologic toxicities during the Induction Period, the patient was assigned as "Yes" to the occurrence of Grade 3 and 4 hematologic toxicities; otherwise, it was "No". If a patient did not have an event, the value of 0 was assigned to that patient.
Number of Participants With at Least 1 Occurrence of Infection Serious Adverse Events (SAEs) Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days. Any occurrence of an infection SAE during the induction treatment period was defined as a binary variable (Yes or No); Yes if total number of febrile neutropenia events ≥ 1 is observed, No for other scenarios. If the patient did not have an event, the value of 0 was assigned to that patient. The criterion for identifying the proper infection SAE records was as follows: if the system organ class (SOC) from Medical Dictionary for Regulatory Activities (MedDRA) Version 20.1 takes value "INFECTIONS AND INFESTATIONS," and the AE was a serious event.
Number of Participants With at Least 1 Occurrence of IV Antibiotic Uses Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days. Occurrence of an IV antibiotics administration during the induction treatment period is defined as a binary variable (Yes or No); Yes if total number of IV antibiotics administration ≥ 1 is observed, No for other scenarios. Each IV antibiotic with a unique start date during the induction treatment period will be defined as a separate event. The criteria for identifying an IV antibiotic administration event was (1) if the therapeutic subgroup from WHO-DD Version September 2017 (ie, TEXT2 for CODE2) takes the value "ANTIBACTERIALS FOR SYSTEMIC USE," and (2) the route of medication was "intravenous" or the route was "other" with the detailed specification as "IVPB."
Number of Participants With at Least 1 Occurrence of Platelet Transfusion Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days. Any occurrence of a platelet transfusion during the induction treatment period was defined as a binary variable (Yes or No); Yes if total number of febrile neutropenia events ≥ 1 is observed, No for other scenarios. If the patient did not have an event, the value of 0 was assigned to that patient. Each platelet transfusion event with a unique start date during the induction treatment period was defined as a separate event.
Number of Participants With Any Cycle Delays and the Number of Cycles Delayed (Induction Period) Induction Period. From date of first dose, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days. After Cycle 1, patients need to meet pre-specified laboratory parameter criteria before initiating Cycle 2 and each subsequent cycle of chemotherapy. A "Cycle Day Status" page asks if the cycle was delayed. If the start of the current cycle was delayed (the site answers "Yes"), this will be counted as a delay. Cycle delays could occur for management of toxicity (hematologic or non-hematologic) or for administrative/logistic reasons. The reason for each cycle delay was captured in the eCRF if it was related to AEs. Reasons other than AEs were not captured.
Number of Participants With Any Cycle Delays and the Number of Cycles Delayed (Maintenance Period) Maintenance Period. From date of first maintenance dose, 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 1160 days. After Cycle 1, patients need to meet pre-specified laboratory parameter criteria before initiating Cycle 2 and each subsequent cycle of chemotherapy. A "Cycle Day Status" page asks if the cycle was delayed. If the start of the current cycle was delayed (the site answers "Yes"), this will be counted as a delay. Cycle delays could occur for management of toxicity (hematologic or non-hematologic) or for administrative/logistic reasons. The reason for each cycle delay was captured in the eCRF if it was related to AEs. Reasons other than AEs were not captured.
Number of Participants With Any Dose Interruptions [for Each Study Drug: Trilaciclib/Placebo, Carboplatin and Etoposide] (Induction Period) Induction Period. From date of first dose, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days. Dose interruptions were defined as interruption of infusion, regardless of whether the study drug was continued after the interruption.
Number of Participants With Any Interrupted Doses of Atezolizumab (Overall Treatment Period) From date of first dose, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 1162 days. Dose interruptions were defined as interruption of infusion, regardless of whether the study drug was continued after the interruption.
Duration of Study Drug Exposure (Induction Period and Maintenance Period) From date of first dose, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 1162 days. Induction period duration of exposure (days) = Day 1 of last induction cycle - Cycle 1 Day 1 of induction phase + 21. Maintenance period duration of exposure (days) = Day 1 of the last maintenance cycle -Cycle 1 Day 1 of maintenance phase + 21.
Number of Cycles Completed (Induction Period and Maintenance Period) From date of first dose, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 49 cycles. Patients were considered to have started a cycle if they have received at least one dose of any study drug (carboplatin, etoposide, atezolizumab or trilaciclib).
Relative Dose Intensity of Trilaciclib/Placebo, Carboplatin, Etoposide, Atezolizumab (Induction Period) and Atezolizumab (Maintenance Period) From date of first dose, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 724 days. Relative dose intensity is defined as 100% times the actual dose intensity divided by the planned dose intensity. The planned dose intensity is defined as the cumulative planned dose through the study divided by (number of cycles \* 3 weeks)
Number of Participants With Any Missed Doses [for Each Study Drug: Trilaciclib/Placebo, Carboplatin and Etoposide] (Induction Period) Induction Period. From date of first dose, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days. Missed doses are identified on the dosing page of each study drug based on the question "Was the dose given?". The missed dose information will be obtained for each study drug. For a study drug, if the last record of response to question "Was the dose given?" is No, it will not be considered as a missed dose but instead considered to be end of treatment if both criteria below are met: (1) No other study drugs are given on the same day, and (2) No study drugs are given subsequently.
Number of Participants With Any Missed Doses of Atezolizumab (Overall Treatment Period) From date of first dose, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 1162 days. Missed doses are identified on the dosing page of each study drug based on the question "Was the dose given?". The missed dose information will be obtained for each study drug. For a study drug, if the last record of response to question "Was the dose given?" is No, it will not be considered as a missed dose but instead considered to be end of treatment if both criteria below are met: (1) No other study drugs are given on the same day, and (2) No study drugs are given subsequently.
Number of Participants With Any Dose Reductions of Carboplatin and Etoposide (Induction Period) Induction Period. From date of first dose, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days. No dose reductions were allowed for trilaciclib or atezolizumab during the study.
Related Research Topics
Explore scientific publications, clinical data analysis, treatment approaches, and expert-compiled information related to the mechanisms and outcomes of this trial. Click any topic for comprehensive research insights.
Trial Locations
- Locations (45)
Loma Linda University
🇺🇸Loma Linda, California, United States
Northside Hospital - Georgia Cancer Specialists
🇺🇸Atlanta, Georgia, United States
Lviv State Regional Treatment and Diagnostics Oncology Center
🇺🇦Lviv, Ukraine
Beverly Hills Cancer Center
🇺🇸Beverly Hills, California, United States
Northern Westchester Hospital
🇺🇸Mount Kisco, New York, United States
Multiprofile Hospital for Active Treatment "Serdika", Sofia
🇧🇬Sofia, Bulgaria
Multiprofile Hospital for Active Treatment "Serdika"
🇧🇬Sofia, Bulgaria
Piedmont Cancer Institute
🇺🇸Atlanta, Georgia, United States
Hospital Universitario Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Hospital 12 de Octubre
🇪🇸Madrid, Spain
Blue Ridge Cancer Care
🇺🇸Blacksburg, Virginia, United States
The Alvin J. Siteman Cancer Center - Center for Advanced Med
🇺🇸Saint Louis, Missouri, United States
H.U. Quirón Dexeus, Hospital Universitario
🇪🇸Barcelona, Spain
Oklahoma University - Peggy and Charles Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Millennium Oncology
🇺🇸Houston, Texas, United States
Horizon Oncology Center
🇺🇸Lafayette, Indiana, United States
St. Louis Cancer Care, LLP, North County
🇺🇸Bridgeton, Missouri, United States
Daugavpils Regional Hospital, Department of Oncology
🇱🇻Daugavpils, Latvia
Centre Oscar Lambret
🇫🇷Lille, France
Hospital Clínico
🇪🇸San Carlos, Madrid, Spain
Hospital Clinic de Barcelona- Servicio de Oncología Médica
🇪🇸Barcelona, Spain
Chernivtsi Regional Clinical Oncology Center
🇺🇦Chernivtsi, Ukraine
St. Jude Heritage Healthcare
🇺🇸Fullerton, California, United States
Singing River Health System
🇺🇸Whittier, California, United States
Joliet Oncology-Hematology Associates
🇺🇸Joliet, Illinois, United States
UCLA Medical Center - Santa Monica Hematology And Oncology
🇺🇸Santa Monica, California, United States
Redwood Regional Medical Group (RRMG) - Fountain Grove
🇺🇸Santa Rosa, California, United States
Trinity Health - Trinity CancerCare Center
🇺🇸Minot, North Dakota, United States
Valley Cancer Associates
🇺🇸Harlingen, Texas, United States
Summit Medical Group, P.A.
🇺🇸Morristown, New Jersey, United States
Virginia Cancer Specialists
🇺🇸Arlington, Virginia, United States
Fort Belvoir Community Hospital
🇺🇸Fort Belvoir, Virginia, United States
CHU Caen De La Côte De Nacre
🇫🇷Caen, France
Pauls Stradiņš Clinical University Hospital, Oncology Clinic
🇱🇻Riga, Latvia
Hospital Teresa Herrera
🇪🇸A Coruña, La Coruña, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
H. Donostia, Hospital Donostia- Servicio de Oncología
🇪🇸San Sebastián, Spain
Hospital Universitario Ntra. Sra. de Valme
🇪🇸Sevilla, Spain
Hospital Arnau de Vilanova
🇪🇸Valencia, Spain
Dnipropetrovsk City Multispecialty Clinical Hospital #4
🇺🇦Dnipro, Ukraine
Complex Oncology Center - Burgas
🇧🇬Burgas, Bulgaria
Gibbs Cancer Center
🇺🇸Spartanburg, South Carolina, United States
East Tallinn Central Hospital Ltd., Clinic of Internal Medicine, Center for Oncology
🇪🇪Tallinn, Estonia
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Hospital Universitario Son Espases
🇪🇸Palma, Islas Baleares, Spain