Carboplatin, Etoposide, and Atezolizumab With or Without Trilaciclib (G1T28), a CDK4/6 Inhibitor, in Extensive-Stage SCLC

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ClinicalTrials.gov Identifier: NCT03041311

Recruitment Status : Terminated (Primary Analysis and survival follow up completed per protocol. Not stopped due to safety concerns.)

First Posted : February 2, 2017

Results First Posted : May 6, 2022

Last Update Posted : May 6, 2022

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

Roche-Genentech

Information provided by (Responsible Party):

G1 Therapeutics, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Small Cell Lung Cancer	Drug: Trilaciclib Drug: Placebo Drug: Carboplatin Drug: Etoposide Drug: Atezolizumab	Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	107 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	Phase 2 Study of Carboplatin, Etoposide, and Atezolizumab With or Without Trilaciclib in Patients With Untreated Extensive-Stage Small Cell Lung Cancer (SCLC)
Actual Study Start Date :	June 29, 2017
Actual Primary Completion Date :	August 17, 2018
Actual Study Completion Date :	October 29, 2020

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Lung cancer

Drug Information available for: Etoposide Carboplatin Etoposide phosphate Trilaciclib Atezolizumab

Genetic and Rare Diseases Information Center resources: Small Cell Lung Cancer

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: trilaciclib+etoposide/carboplatin/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.	Drug: Trilaciclib Trilaciclib IV Other Name: G1T28 Drug: Carboplatin Carboplatin IV Other Name: Paraplatin Drug: Etoposide Etoposide IV Other Name: VP-16 Drug: Atezolizumab Atezolizumab IV Other Name: Tecentriq
Experimental: placebo+etoposide/carboplatin/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.	Drug: Placebo Placebo IV Drug: Carboplatin Carboplatin IV Other Name: Paraplatin Drug: Etoposide Etoposide IV Other Name: VP-16 Drug: Atezolizumab Atezolizumab IV Other Name: Tecentriq

Arm

Intervention/treatment

Experimental: trilaciclib+etoposide/carboplatin/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.

Drug: Trilaciclib

Trilaciclib IV

Other Name: G1T28

Drug: Carboplatin

Carboplatin IV

Other Name: Paraplatin

Drug: Etoposide

Etoposide IV

Other Name: VP-16

Drug: Atezolizumab

Atezolizumab IV

Other Name: Tecentriq

Experimental: placebo+etoposide/carboplatin/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.

Drug: Placebo

Placebo IV

Drug: Carboplatin

Carboplatin IV

Other Name: Paraplatin

Drug: Etoposide

Etoposide IV

Other Name: VP-16

Drug: Atezolizumab

Atezolizumab IV

Other Name: Tecentriq

Outcome Measures

Primary Outcome Measures :

Duration of Severe (Grade 4) Neutropenia in Cycle 1 [ Time Frame: 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 [ Time Frame: 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 :

All-Cause Dose Reductions [ Time Frame: 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.
Number of Participants With at Least 1 Occurrence of RBC Transfusion on/After Week 5 (Proportion of Patients) [ Time Frame: 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.
Occurrence of Granulocyte Colony-Stimulating Factor (G-CSF) Administration (Proportion of Patients) [ Time Frame: 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.
Overall Survival (OS) [ Time Frame: 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.
Major Adverse Hematologic Events (MAHE) (Composite Endpoint) [ Time Frame: 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.
Best Overall Response [ Time Frame: 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.
Duration of Objective Response (Complete Response or Partial Response) [ Time Frame: 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.
Progression-Free Survival [ Time Frame: 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.
Number of Participants With at Least 1 Occurrence of Febrile Neutropenia [ Time Frame: 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.
Number of Participants With at Least 1 Occurrence of Grade 3 or 4 Hematologic Laboratory Abnormalities [ Time Frame: 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 Erythropoiesis Stimulating Agent (ESA) Administration [ Time Frame: 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 Platelet Transfusion [ Time Frame: 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 at Least 1 Occurrence of Infection Serious Adverse Events (SAEs) [ Time Frame: 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 Pulmonary Infection Serious Adverse Events (SAEs) [ Time Frame: 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.
Number of Participants With at Least 1 Occurrence of IV Antibiotic Uses [ Time Frame: 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."
Duration of Study Drug Exposure (Induction Period and Maintenance Period) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 Cycle Delays and the Number of Cycles Delayed (Induction Period) [ Time Frame: 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) [ Time Frame: 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 Missed Doses [for Each Study Drug: Trilaciclib/Placebo, Carboplatin and Etoposide] (Induction Period) [ Time Frame: 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) [ Time Frame: 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 Interruptions [for Each Study Drug: Trilaciclib/Placebo, Carboplatin and Etoposide] (Induction Period) [ Time Frame: 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) [ Time Frame: 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.
Number of Participants With Any Dose Reductions of Carboplatin and Etoposide (Induction Period) [ Time Frame: 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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Key Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03041311

Locations

Show 45 study locations

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United States, California
Beverly Hills Cancer Center
Beverly Hills, California, United States, 90211
St. Jude Heritage Healthcare
Fullerton, California, United States, 92835
Loma Linda University
Loma Linda, California, United States, 92350
UCLA Medical Center - Santa Monica Hematology And Oncology
Santa Monica, California, United States, 90404
Redwood Regional Medical Group (RRMG) - Fountain Grove
Santa Rosa, California, United States, 95403
Singing River Health System
Whittier, California, United States, 90603
United States, Georgia
Piedmont Cancer Institute
Atlanta, Georgia, United States, 30318
Northside Hospital - Georgia Cancer Specialists
Atlanta, Georgia, United States, 30341
United States, Illinois
Joliet Oncology-Hematology Associates
Joliet, Illinois, United States, 60435
United States, Indiana
Horizon Oncology Center
Lafayette, Indiana, United States, 47905
United States, Louisiana
Ochsner Clinic Foundation
New Orleans, Louisiana, United States, 70121
United States, Missouri
St. Louis Cancer Care, LLP, North County
Bridgeton, Missouri, United States, 63044
The Alvin J. Siteman Cancer Center - Center for Advanced Med
Saint Louis, Missouri, United States, 63110-1094
United States, New Jersey
Summit Medical Group, P.A.
Morristown, New Jersey, United States, 07962
United States, New York
Northern Westchester Hospital
Mount Kisco, New York, United States, 10549
United States, North Dakota
Trinity Health - Trinity CancerCare Center
Minot, North Dakota, United States, 58701
United States, Oklahoma
Oklahoma University - Peggy and Charles Stephenson Cancer Center
Oklahoma City, Oklahoma, United States, 73117
United States, South Carolina
Gibbs Cancer Center
Spartanburg, South Carolina, United States, 29303
United States, Texas
Valley Cancer Associates
Harlingen, Texas, United States, 78550
Millennium Oncology
Houston, Texas, United States, 77090
United States, Virginia
Virginia Cancer Specialists
Arlington, Virginia, United States, 22031
Blue Ridge Cancer Care
Blacksburg, Virginia, United States, 24060
Fort Belvoir Community Hospital
Fort Belvoir, Virginia, United States, 22060
Bulgaria
Complex Oncology Center - Burgas
Burgas, Bulgaria, 8000
Multiprofile Hospital for Active Treatment "Serdika", Sofia
Sofia, Bulgaria, 1303
Multiprofile Hospital for Active Treatment "Serdika"
Sofia, Bulgaria, 1303
Estonia
East Tallinn Central Hospital Ltd., Clinic of Internal Medicine, Center for Oncology
Tallinn, Estonia, 11312
France
CHU Caen De La Côte De Nacre
Caen, France, 14033
Centre Oscar Lambret
Lille, France, 59020
Latvia
Daugavpils Regional Hospital, Department of Oncology
Daugavpils, Latvia, LV-5417
Pauls Stradiņš Clinical University Hospital, Oncology Clinic
Riga, Latvia, LV-1002
Spain
Hospital Universitario Son Espases
Palma, Islas Baleares, Spain, 07120
Hospital Teresa Herrera
A Coruña, La Coruña, Spain, 15006
Hospital Universitario Puerta de Hierro Majadahonda
Majadahonda, Madrid, Spain, 28222
Hospital Clínico
San Carlos, Madrid, Spain, 28040
H.U. Quirón Dexeus, Hospital Universitario
Barcelona, Spain, 08028
Hospital Clinic de Barcelona- Servicio de Oncología Médica
Barcelona, Spain, 08036
Hospital Universitario Ramón y Cajal
Madrid, Spain, 28034
Hospital 12 de Octubre
Madrid, Spain, 28041
H. Donostia, Hospital Donostia- Servicio de Oncología
San Sebastián, Spain, 20014
Hospital Universitario Ntra. Sra. de Valme
Sevilla, Spain, 41014
Hospital Arnau de Vilanova
Valencia, Spain, 46015
Ukraine
Chernivtsi Regional Clinical Oncology Center
Chernivtsi, Ukraine, 58013
Dnipropetrovsk City Multispecialty Clinical Hospital #4
Dnipro, Ukraine, 49102
Lviv State Regional Treatment and Diagnostics Oncology Center
Lviv, Ukraine, 79031

Sponsors and Collaborators

G1 Therapeutics, Inc.

Roche-Genentech

Investigators

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Study Director:	Clinical Contact	G1 Therapeutics, Inc.

Study Documents (Full-Text)

Documents provided by G1 Therapeutics, Inc.:

Study Protocol [PDF] September 14, 2018

Statistical Analysis Plan: Region 2 [PDF] November 1, 2018

More Information

Publications:

Daniel D, Kuchava V, Bondarenko I, Ivashchuk O, Reddy S, Jaal J, Kudaba I, Hart L, Matitashvili A, Pritchett Y, Morris SR, Sorrentino JA, Antal JM, Goldschmidt J. Trilaciclib prior to chemotherapy and atezolizumab in patients with newly diagnosed extensive-stage small cell lung cancer: A multicentre, randomised, double-blind, placebo-controlled Phase II trial. Int J Cancer. 2020 Dec 21;148(10):2557-70. doi: 10.1002/ijc.33453. Online ahead of print.

Weiss J, Goldschmidt J, Andric Z, Dragnev KH, Gwaltney C, Skaltsa K, Pritchett Y, Antal JM, Morris SR, Daniel D. Effects of Trilaciclib on Chemotherapy-Induced Myelosuppression and Patient-Reported Outcomes in Patients with Extensive-Stage Small Cell Lung Cancer: Pooled Results from Three Phase II Randomized, Double-Blind, Placebo-Controlled Studies. Clin Lung Cancer. 2021 Sep;22(5):449-460. doi: 10.1016/j.cllc.2021.03.010. Epub 2021 Mar 26.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Abraham I, Onyekwere U, Deniz B, Moran D, Chioda M, MacDonald K, Huang H. Trilaciclib and the economic value of multilineage myeloprotection from chemotherapy-induced myelosuppression among patients with extensive-stage small cell lung cancer treated with first-line chemotherapy. J Med Econ. 2021 Nov;24(sup1):71-83. doi: 10.1080/13696998.2021.2014163.

Zeng R, Liu F, Fang C, Yang J, Luo L, Yue P, Gao B, Dong Y, Xiang Y. PIV and PILE Score at Baseline Predict Clinical Outcome of Anti-PD-1/PD-L1 Inhibitor Combined With Chemotherapy in Extensive-Stage Small Cell Lung Cancer Patients. Front Immunol. 2021 Oct 29;12:724443. doi: 10.3389/fimmu.2021.724443. eCollection 2021.

Hussein M, Maglakelidze M, Richards DA, Sabatini M, Gersten TA, Lerro K, Sinielnikov I, Spira A, Pritchett Y, Antal JM, Malik R, Beck JT. Myeloprotective Effects of Trilaciclib Among Patients with Small Cell Lung Cancer at Increased Risk of Chemotherapy-Induced Myelosuppression: Pooled Results from Three Phase 2, Randomized, Double-Blind, Placebo-Controlled Studies. Cancer Manag Res. 2021 Aug 9;13:6207-6218. doi: 10.2147/CMAR.S313045. eCollection 2021.

Ferrarotto R, Anderson I, Medgyasszay B, Garcia-Campelo MR, Edenfield W, Feinstein TM, Johnson JM, Kalmadi S, Lammers PE, Sanchez-Hernandez A, Pritchett Y, Morris SR, Malik RK, Csoszi T. Trilaciclib prior to chemotherapy reduces the usage of supportive care interventions for chemotherapy-induced myelosuppression in patients with small cell lung cancer: Pooled analysis of three randomized phase 2 trials. Cancer Med. 2021 Sep;10(17):5748-5756. doi: 10.1002/cam4.4089. Epub 2021 Aug 18.

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Responsible Party:	G1 Therapeutics, Inc.
ClinicalTrials.gov Identifier:	NCT03041311
Other Study ID Numbers:	G1T28-05 2017-000358-20 ( EudraCT Number )
First Posted:	February 2, 2017 Key Record Dates
Results First Posted:	May 6, 2022
Last Update Posted:	May 6, 2022
Last Verified:	April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by G1 Therapeutics, Inc.:


Small Cell Lung Cancer CDK4/6 Inhibitor Immune Checkpoint Inhibitor

Additional relevant MeSH terms:

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Lung Neoplasms Small Cell Lung Carcinoma Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms Carboplatin	Etoposide Atezolizumab Antineoplastic Agents Antineoplastic Agents, Phytogenic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Immune Checkpoint Inhibitors Antineoplastic Agents, Immunological

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