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Trilaciclib (G1T28), a CDK 4/6 Inhibitor, in Combination With Etoposide and Carboplatin in Extensive Stage Small Cell Lung Cancer (SCLC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02499770
Recruitment Status : Completed
First Posted : July 16, 2015
Results First Posted : July 9, 2020
Last Update Posted : August 21, 2020
Sponsor:
Information provided by (Responsible Party):
G1 Therapeutics, Inc.

Brief Summary:

This is a study to investigate the potential clinical benefit of trilaciclib (G1T28) in preserving the bone marrow and the immune system, and enhancing chemotherapy antitumor efficacy when administered prior to carboplatin and etoposide in first line treatment for patients with newly diagnosed extensive-stage SCLC.

The study consists of 2 parts: a limited open-label, dose-finding portion (Part 1), and a randomized double-blind portion (Part 2). Both parts include 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase begins on the day of first dose with study treatment and completes at the Post-Treatment Visit. Approximately, 90 patients will be enrolled in the study; 20 patients in the Part 1 and 70 patients in the Part 2 portion.


Condition or disease Intervention/treatment Phase
Small Cell Lung Cancer Drug: Carboplatin Drug: Placebo Drug: Trilaciclib Drug: Etoposide Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 122 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Phase 1b/2a Safety and Pharmacokinetic Study of G1T28 in Patients With Extensive Stage Small Cell Lung Cancer (SCLC) Receiving Etoposide and Carboplatin
Actual Study Start Date : June 26, 2015
Actual Primary Completion Date : July 3, 2017
Actual Study Completion Date : February 22, 2019


Arm Intervention/treatment
Experimental: trilaciclib + carboplatin/etoposide
All patients in part 1 will receive trilaciclib (G1T28) prior to standard chemotherapy- carboplatin and etoposide. Patients will have PK assessments completed on days 1 and 3 in cycle 1 only. All patents will be monitored for safety and tumor response based on RECIST version 1.1. Safety surveillance reporting of AEs and concomitant medications commences at the time that informed consent is obtained and continues through the Post Treatment Visit.
Drug: Carboplatin
Other Name: Paraplatin

Drug: Trilaciclib
Other Name: G1T28

Drug: Etoposide
Other Names:
  • VP-16
  • Toposar

Experimental: trilaciclib/placebo + carboplatin/etoposide
All patients enrolled in part 2 will be randomized to receive either trilaciclib (G1T28) or placebo administered prior to standard chemotherapy- carboplatin and etoposide. All patents will be monitored for safety and tumor response based on RECIST version 1.1. Safety surveillance reporting of AEs and concomitant medications commences at the time that informed consent is obtained and continues through the Post Treatment Visit.
Drug: Carboplatin
Other Name: Paraplatin

Drug: Placebo
Drug: Trilaciclib
Other Name: G1T28

Drug: Etoposide
Other Names:
  • VP-16
  • Toposar




Primary Outcome Measures :
  1. Number of Participants With Dose Limiting Toxicities by Cohort in Cycle 1, Part 1 [ Time Frame: Days 1-21 of Cycle 1 ]

    Dose-limiting toxicities (DLTs) were drug-related toxicities defined as follows:

    1. Absolute neutrophil count (ANC) < 0.5 × 10^9/L lasting for ≥ 7 days
    2. ≥ Grade 3 neutropenic infection/febrile neutropenia
    3. Grade 4 thrombocytopenia (TCP) or ≥ Grade 3 TCP with bleeding
    4. 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
    5. ≥ Grade 3 nonhematologic toxicity (nausea, vomiting, and diarrhea failing maximal medical management; fatigue lasting for > 72 hours)

    Toxicities not clearly related to etoposide/carboplatin therapy were also considered for the purposes of determining DLTs.


  2. Incidence of Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Related AEs, Related SAEs, and AEs Leading to Study Drug Discontinuation in Part 1 [ Time Frame: TEAEs were any AE that started on or after the first dose of study drug and up to the last dose +30 days (a minimum of 51 days up to a maximum of 374 days) ]
    An AE was defined as any untoward medical occurrence in a participant administered a medicinal product that did not necessarily have a causal relationship with this treatment. TEAEs were defined as any AE that started on or after the first dose of study drug and up to the last dose +30 days. SAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect. Relatedness to study drug was assessed by the investigator. Related refers to those events that were Possibly, Probably, or Definitely Related. AEs with an unknown/not reported onset date were also included.

  3. Duration of Severe (Grade 4) Neutropenia in Part 2 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Severe (Grade 4) neutropenia was defined as at least 1 ANC value <0.5 × 10^9/L during the treatment period. Within each cycle, the duration (days) of severe neutropenia 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. The duration of severe neutropenia only included participants who had at least 1 severe neutropenia event in the cycle, and censoring rules were applied for unresolved severe neutropenia in a cycle. For the treatment period, the overall duration of severe neutropenia was the median value among the durations from all cycles.


Secondary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) of Trilaciclib in Cycle 1, Part 1 [ Time Frame: Days 1 and 3 of Cycle 1 for a 21-day cycle ]
    Cmax of trilaciclib in plasma was determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used. For estimation of Cmax, a concentration that was below the limit of quantification (BLQ) was assigned a value of zero if it occurred in a profile before the first measurable concentration. If a BLQ value occurred after a measurable concentration in a profile, and was followed by a value above the lower limit of quantification, then the BLQ was treated as missing data. If a BLQ value occurred at the end of the collection interval (after the last quantifiable concentration) it was treated as missing data. If two BLQ values occurred in succession after Cmax, the profile was deemed to have terminated at the first BLQ value and any subsequent concentrations were omitted.

  2. Area Under the Plasma Concentration Versus Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) for Trilaciclib in Cycle 1, Part 1 [ Time Frame: Days 1 and 3 of Cycle 1 for a 21-day cycle ]
    AUC0-inf of trilaciclib in plasma was determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used.

  3. Time of Maximum Observed Concentration (Tmax) of Trilaciclib in Cycle 1, Part 1 [ Time Frame: Days 1 and 3 of Cycle 1 for a 21-day cycle ]
    Tmax of trilaciclib in plasma was determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used.

  4. Cmax of Etoposide and Free and Total Carboplatin in Cycle 1, Part 1 [ Time Frame: Days 1 and 3 of Cycle 1 for a 21-day cycle (carboplatin was only dosed on Day 1 so there are no Day 3 Cmax values) ]
    Cmax of etoposide and free and total carboplatin in plasma were determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used. For estimation of Cmax, a concentration that was BLQ was assigned a value of zero if it occurred in a profile before the first measurable concentration. If a BLQ value occurred after a measurable concentration in a profile, and was followed by a value above the lower limit of quantification, then the BLQ was treated as missing data. If a BLQ value occurred at the end of the collection interval (after the last quantifiable concentration) it was treated as missing data. If two BLQ values occurred in succession after Cmax, the profile was deemed to have terminated at the first BLQ value and any subsequent concentrations were omitted.

  5. AUC0-inf of Etoposide and Free and Total Carboplatin in Cycle 1, Part 1 [ Time Frame: Days 1 and 3 of Cycle 1 for a 21-day cycle (carboplatin was only dosed on Day 1 so there are no Day 3 AUC0-inf values) ]
    AUC0-inf of etoposide and free and total carboplatin in plasma were determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used.

  6. Tmax of Etoposide and Free and Total Carboplatin in Cycle 1, Part 1 [ Time Frame: Days 1 and 3 of Cycle 1 for a 21-day cycle (carboplatin was only dosed on Day 1 so there are no Day 3 Tmax values) ]
    Tmax of etoposide and free and total carboplatin in plasma was determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used.

  7. Duration of Severe (Grade 4) Neutropenia in Part 1 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Severe (Grade 4) neutropenia was defined as at least 1 ANC value <0.5 × 10^9/L during the treatment period. Within each cycle, the duration (days) of severe neutropenia 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. The duration of severe neutropenia only included participants who had at least 1 severe neutropenia event in the cycle, and censoring rules were applied for unresolved severe neutropenia in a cycle. For the treatment period, the overall duration of severe neutropenia was the median value among the durations from all cycles.

  8. Occurrence of Severe (Grade 4) Neutropenia in Part 1 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Severe (Grade 4) neutropenia was defined as at least 1 ANC value <0.5 × 10^9/L during the treatment period.

  9. Occurrence of Febrile Neutropenia in Part 1 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Each febrile neutropenia event (as defined by Common Terminology Criteria for Adverse Events [CTCAE]) was captured as an AE. The occurrence of febrile neutropenia was defined as at least 1 febrile neutropenia event during the treatment period. For the treatment period, the total number of febrile neutropenia events was the number of febrile neutropenia events with a unique start date.

  10. Duration of Grade 3/4 Neutropenia in Part 1 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Grade 3/4 neutropenia was defined as at least 1 ANC value <1.0 × 10^9/L during the treatment period. Within each cycle, duration (days) of Grade 3/4 neutropenia was defined as the number of days from the date of the first ANC value of <1.0 × 10^9/L observed between start of cycle and end of cycle to the date of the first ANC value ≥1.0 × 10^9/L that met the following criteria: 1) occurred after the ANC value of <1.0 × 10^9/L and 2) no other ANC values <1.0 × 10^9/L occurred between this day and end of cycle. The duration of Grade 3/4 neutropenia only included participants who had at least 1 Grade 3/4 neutropenia event in the cycle, and censoring rules were applied for unresolved Grade 3/4 neutropenia in a cycle. For the treatment period, the overall duration of Grade 3/4 neutropenia was the median value among the durations of Grade 3/4 neutropenia from all cycles.

  11. Occurrence of Grade 3/4 Neutropenia in Part 1 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Grade 3/4 neutropenia was defined as at least 1 ANC value <1.0 × 10^9/L during the treatment period.

  12. Nadir of Absolute Neutrophil Count in Cycle 1, Part 1 [ Time Frame: From baseline to the end of Cycle 1 ]
    Cycle nadir was the lowest value for ANC that occurred between start of cycle and end of cycle and was less than the cycle baseline.

  13. Occurrence of Granulocyte-Colony Stimulating Factor (G-CSF) Administration in Part 1 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Administration of G-CSF was collected with concomitant medications, which were coded using World Health Organization Drug Dictionary (WHO-DD) Version September 2017. A cycle where G-CSF was administered concurrently was identified by comparing the start and stop dates of each administration of G-CSF to the start of cycle and end of cycle. The occurrence of G-CSF administrations was defined as at least 1 cycle with G-CSF administrations during the treatment period. For the treatment period, the total number of G-CSF administrations was the number of cycles with G-CSF administrations.

  14. Occurrence of Red Blood Cell (RBC) Transfusion in Part 1 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Within a cycle, a RBC transfusion event was defined as either 1) an actual RBC transfusion, or 2) eligible for RBC transfusion (defined as hemoglobin <8.0 g/dL). The occurrence of RBC transfusions was defined as at least 1 cycle with RBC transfusion during the treatment period. For the treatment period, the total number of RBC transfusions was the number of cycles with RBC transfusions.

  15. Change From Baseline of Hemoglobin at the End of Cycle 6, Part 1 [ Time Frame: Baseline, Day 1, Day 3, Day 8, Day 10, and Day 15 of a 21-day cycle x 6 ]
    Blood samples were collected for local clinical laboratory assessment of hemoglobin levels.

  16. Occurrence of Erythropoietin Stimulating Agent (ESA) Administration in Part 1 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Administration of ESAs was collected with concomitant medications, which were coded using WHO-DD Version September 2017. A cycle where an ESA was administered concurrently was identified by comparing the start and stop dates of each administration of an ESA to the start of cycle and end of cycle. The occurrence of ESA administration was at least 1 cycle with an ESA administration during the treatment period. For the treatment period, the total number of ESA administrations was the number of cycles with ESA administrations.

  17. Occurrence of Platelet Transfusion in Part 1 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Within a cycle, a platelet transfusion event was defined as either 1) an actual platelet transfusion, or 2) eligible for platelet transfusion (defined as a platelet count ≤10 × 10^9/L). The occurrence of platelet transfusions was defined as at least 1 cycle with platelet transfusion during the treatment period. For the treatment period, the total number of platelet transfusions was the number of cycles with platelet transfusions.

  18. Change From Baseline of Platelet Count at the End of Cycle 6, Part 1 [ Time Frame: Baseline, Day 1, Day 3, Day 8, Day 10, and Day 15 of a 21-day cycle x 6 ]
    Blood samples were collected for local clinical laboratory assessment of platelet count.

  19. Change From Baseline of Lymphocyte Count at the End of Cycle 6, Part 1 [ Time Frame: Baseline, Day 1, Day 3, Day 8, Day 10, and Day 15 of a 21-day cycle x 6 ]
    Blood samples were collected for local clinical laboratory assessment of lymphocyte count.

  20. Occurrence of Dose Reduction in Part 1 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Dose reductions were not permitted for trilaciclib, per study protocol. Dose reductions for E/P were derived from changes in the protocol-specified dose on the dosing page and corresponded to the reductions for toxicity specified in the protocol. No more than 2 dose reductions of E/P in total were allowed for any participant. Simultaneous reductions in the doses of E/P were counted as 1 dose reduction. For the treatment period, the total number of dose reductions was the number of cycles where there was at least 1 dose reduction.

  21. Occurrence of Infectious SAEs in Part 1 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    SAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect. An infectious SAE was a serious event in the Medical Dictionary for Regulatory Activities (MedDRA) system organ class "infections and infestations" and a preferred term of anal abscess, bacteraemia, bronchitis, candida infection, chronic sinusitis, conjunctivitis, infection, influenza, nasopharyngitis, oral candidiasis, oral herpes, pharyngitis streptococcal, pneumonia, pneumonia bacterial, respiratory tract infection, sepsis, skin infection, upper respiratory tract infection, urinary tract infection, urosepsis or viral upper respiratory tract infection.

  22. Occurrence of Pulmonary Infection SAE in Part 1 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    SAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect. A pulmonary infection SAE was a serious event in the MedDRA system organ class "infections and infestations" and a preferred term of bronchitis, influenza, pneumonia, pneumonia bacterial, respiratory tract infection, upper respiratory tract infection or viral upper respiratory tract infection.

  23. Occurrence of IV Antibiotic Administration in Part 1 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Intravenous antibiotic administration was collected with concomitant medications, which were coded using WHO-DD Version September 2017. A cycle where IV antibiotic was administered concurrently was identified by comparing the start and stop dates of each administration of IV antibiotic to the start of cycle and end of cycle. The occurrence of IV antibiotic administration was defined as at least 1 cycle with IV antibiotic administration during the treatment period. For the treatment period, the total number of IV antibiotic administrations was the number of cycles with IV antibiotic administrations.

  24. Time to First Major Adverse Hematologic Event (MAHE) in Part 1 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    MAHE was a composite endpoint incorporating the measurement of several clinically meaningful aspects of myelopreservation into a single endpoint. The individual components for MAHE were hospitalization for a hematologic event, febrile neutropenia, death related to treatment, dose delay/reduction due to ANC or platelet counts, prolonged severe neutropenia (duration >5 days), RBC transfusion (actual or eligible) and platelet transfusion (actual or eligible). Time to first occurrence of a MAHE event was defined as the first time to observe an interested event among all the components, starting from the first dose date of study drug administration.

  25. Best Overall Tumor Response Based on Assessments in Part 1 [ Time Frame: Baseline, end of every two 21-day cycles, up until disease progression to a maximum of the time at least 70% overall survival (OS) events observed (a maximum of 4 years) ]
    Tumor response was assessed by computed tomography (CT) or magnetic resonance imaging (MRI). Overall visit response by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 was derived programmatically using data from target lesions (TLs), non-target lesions (NTLs), & new lesions. Tumor response data were used to determine each participant's time point response & best overall response (BOR). Complete response (CR) was disappearance of all TLs, any pathological lymph nodes selected as TLs must have reduced in short axis to <10 mm. Partial response (PR) was at least a 30% decrease from baseline in the sum of diameters of TLs, as long as criteria for progressive disease (PD) were not met. PD was a ≥20% increase in the smallest sum of diameters of TLs since treatment started (including baseline) and an absolute increase of ≥5 mm. Stable disease (SD) was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

  26. Best Overall Tumor Response Based on Blinded Independent Central Review (BICR) Assessments in Part 1 [ Time Frame: Baseline, end of every two 21-day cycles, up until disease progression to a maximum of the time at least 70% OS events observed (a maximum of 4 years) ]
    Tumor response was assessed by CT or MRI. Overall visit response by RECIST v1.1 was determined by BICR. Tumor response data were used to determine each participant's time point response & BOR. CR was disappearance of all TLs, any pathological lymph nodes selected as TLs must have reduced in short axis to <10 mm. PR was at least a 30% decrease from baseline in the sum of diameters of TLs, as long as criteria for PD were not met. PD was a ≥20% increase in the smallest sum of diameters of TLs since treatment started (including baseline) and an absolute increase of ≥5 mm. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

  27. Progression Free Survival (PFS) Based on Assessments in Part 1 [ Time Frame: Baseline, end of every two 21-day cycles, up until disease progression to a maximum of the time at least 70% OS events observed (a maximum of 4 years) ]
    Tumor response was assessed by CT or MRI. PFS was defined as the time (months) from date of first dose date of study drug for participants in Part 1 until date of documented disease progression or death due to any cause, whichever occurred first. More specifically, PFS was determined using all the assessment data up until the last evaluable visit prior to or on the date of i) disease progression as defined by RECIST 1.1 or by clinical criteria as determined by the investigator; or ii) withdrawal of consent; or iii) receiving subsequent anticancer therapy, whichever was earlier. For PFS determined using response data derived programmatically, either clinical progression or progression by RECIST (whichever came first) was considered. Median and inter-quartile range of PFS were calculated using the Kaplan-Meier method.

  28. OS in Part 1 [ Time Frame: Baseline up until death or a maximum of the time at least 70% OS events observed (a maximum of 4 years) ]
    OS was calculated as the time (months) from date of first dose of study drug for participants in Part 1 to the date of death due to any cause. Participants who did not die during the study were censored at the date last known to be alive. Participants lacking data beyond the day of first dose of study drug had their survival time censored at day of first dose of study drug. OS was not censored if a participant received other anti-tumor treatments after the study drugs. Median and inter-quartile range of OS were calculated using the Kaplan-Meier method.

  29. Occurrence of Severe (Grade 4) Neutropenia in Part 2 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Severe (Grade 4) neutropenia was defined as at least 1 ANC value <0.5 × 10^9/L during the treatment period.

  30. Occurrence of Febrile Neutropenia in Part 2 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Each febrile neutropenia event (as defined by CTCAE) was captured as an AE. The occurrence of febrile neutropenia was defined as at least 1 febrile neutropenia event during the treatment period. For the treatment period, the total number of febrile neutropenia events was the number of febrile neutropenia events with a unique start date.

  31. Duration of Grade 3/4 Neutropenia in Part 2 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Grade 3/4 neutropenia was defined as at least 1 ANC value <1.0 × 10^9/L during the treatment period. Within each cycle, duration (days) of Grade 3/4 neutropenia was defined as the number of days from the date of the first ANC value of <1.0 × 10^9/L observed between start of cycle and end of cycle to the date of the first ANC value ≥1.0 × 10^9/L that met the following criteria: 1) occurred after the ANC value of <1.0 × 10^9/L and 2) no other ANC values <1.0 × 10^9/L occurred between this day and end of cycle. The duration of Grade 3/4 neutropenia only included participants who had at least 1 Grade 3/4 neutropenia event in the cycle, and censoring rules were applied for unresolved Grade 3/4 neutropenia in a cycle. For the treatment period, the overall duration of Grade 3/4 neutropenia was the median value among the durations of Grade 3/4 neutropenia from all cycles.

  32. Occurrence of Grade 3/4 Neutropenia in Part 2 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Grade 3/4 neutropenia was defined as at least 1 ANC value <1.0 × 10^9/L during the treatment period.

  33. Nadir of Absolute Neutrophil Count in Cycle 1, Part 2 [ Time Frame: From baseline to the end of Cycle 1 ]
    Cycle nadir was the lowest value for ANC that occurred between start of cycle and end of cycle and was less than the cycle baseline.

  34. Occurrence of G-CSF Administration in Part 2 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Administration of G-CSF was collected with concomitant medications, which were coded using WHO-DD Version September 2017. A cycle where G-CSF was administered concurrently was identified bycomparing the start and stop dates of each administration of G-CSF to the start of cycle and end of cycle. The occurrence of G-CSF administrations was defined as at least 1 cycle with G-CSF administrations during the treatment period. For the treatment period, the total number of G-CSF administrations was the number of cycles with G-CSF administrations.

  35. Occurrence of RBC Transfusion in Part 2 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Within a cycle, a RBC transfusion event was defined as either 1) an actual RBC transfusion, or 2) eligible for RBC transfusion (defined as hemoglobin <8.0 g/dL). The occurrence of RBC transfusions was defined as at least 1 cycle with RBC transfusion during the treatment period. For the treatment period, the total number of RBC transfusions was the number of cycles with RBC transfusions. If a participant did not have any RBC transfusions, they were assigned a value of 0.

  36. Change From Baseline of Hemoglobin at the End of Cycle 6, Part 2 [ Time Frame: Baseline, Day 1, Day 3, Day 8, Day 10, and Day 15 of a 21-day cycle x 6 ]
    Blood samples were collected for local clinical laboratory assessment of hemoglobin levels.

  37. Occurrence of ESA Administration in Part 2 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Administration of ESAs was collected with concomitant medications, which were coded using WHO-DD Version September 2017. A cycle where an ESA was administered concurrently was identified by comparing the start and stop dates of each administration of an ESA to the start of cycle and end of cycle. The occurrence of ESA administration was at least 1 cycle with an ESA administration during the treatment period. For the treatment period, the total number of ESA administrations was the number of cycles with ESA administrations.

  38. Occurrence of Platelet Transfusion in Part 2 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Within a cycle, a platelet transfusion event was defined as either 1) an actual platelet transfusion, or 2) eligible for platelet transfusion (defined as a platelet count ≤10 × 10^9/L). The occurrence of platelet transfusions was defined as at least 1 cycle with platelet transfusion during the treatment period. For the treatment period, the total number of platelet transfusions was the number of cycles with platelet transfusions.

  39. Change From Baseline of Platelet Count at the End of Cycle 6, Part 2 [ Time Frame: Baseline, Day 1, Day 3, Day 8, Day 10, and Day 15 of a 21-day cycle x 6 ]
    Blood samples were collected for local clinical laboratory assessment of platelet count.

  40. Change From Baseline of Lymphocyte Count at the End of Cycle 6, Part 2 [ Time Frame: Baseline, Day 1, Day 3, Day 8, Day 10, and Day 15 of a 21-day cycle x 6 ]
    Blood samples were collected for local clinical laboratory assessment of lymphocyte count.

  41. Occurrence of Dose Reduction in Part 2 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Dose reductions were not permitted for trilaciclib, per study protocol. Dose reductions for E/P were derived from changes in the protocol-specified dose on the dosing page and corresponded to the reductions for toxicity specified in the protocol. No more than 2 dose reductions of E/P in total were allowed for any participant. Simultaneous reductions in the doses of E/P were counted as 1 dose reduction. For the treatment period, the total number of dose reductions was the number of cycles where there was at least 1 dose reduction.

  42. Occurrence of Infectious SAEs in Part 2 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    SAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect. An infectious SAE was a serious event in the MedDRA system organ class "infections and infestations" and a preferred term of anal abscess, bacteraemia, bronchitis, candida infection, chronic sinusitis, conjunctivitis, infection, influenza, nasopharyngitis, oral candidiasis, oral herpes, pharyngitis streptococcal, pneumonia, pneumonia bacterial, respiratory tract infection, sepsis, skin infection, upper respiratory tract infection, urinary tract infection, urosepsis or viral upper respiratory tract infection.

  43. Occurrence of Pulmonary Infection SAE in Part 2 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    SAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect. A pulmonary infection SAE was a serious event in the MedDRA system organ class "infections and infestations" and a preferred term of bronchitis, influenza, pneumonia, pneumonia bacterial, respiratory tract infection, upper respiratory tract infection or viral upper respiratory tract infection.

  44. Occurrence of IV Antibiotic Administration in Part 2 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    Intravenous antibiotic administration was collected with concomitant medications, which were coded using WHO-DD Version September 2017. A cycle where IV antibiotic was administered concurrently was identified by comparing the start and stop dates of each administration of IV antibiotic to the start of cycle and end of cycle. The occurrence of IV antibiotic administration was defined as at least 1 cycle with IV antibiotic administration during the treatment period. For the treatment period, the total number of IV antibiotic administrations was the number of cycles with IV antibiotic administrations.

  45. Time to First MAHE in Part 2 [ Time Frame: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days) ]
    MAHE was a composite endpoint incorporating the measurement of several clinically meaningful aspects of myelopreservation into a single endpoint. The individual components for MAHE were hospitalization for a hematologic event, febrile neutropenia, death related to treatment, dose delay/reduction due to ANC or platelet counts, prolonged severe neutropenia (duration >5 days), RBC transfusion (actual or eligible) and platelet transfusion (actual or eligible). Time to first occurrence of a MAHE event was defined as the first time to observe an interested event among all the components, starting from the first dose date of study drug administration.

  46. Best Overall Tumor Response Based on Assessments in Part 2 [ Time Frame: Baseline, end of every two 21-day cycles, up until disease progression to a maximum of the time at least 70% OS events observed (a maximum of 4 years) ]
    Tumor response was assessed by CT or MRI. Overall visit response by RECIST v1.1 was derived programmatically using data from TLs, NTLs, & new lesions. Tumor response data were used to determine each participant's time point response & BOR. CR was disappearance of all TLs, any pathological lymph nodes selected as TLs must have reduced in short axis to <10 mm. PR was at least a 30% decrease from baseline in the sum of diameters of TLs, as long as criteria for PD were not met. PD was a ≥20% increase in the smallest sum of diameters of TLs since treatment started (including baseline) and an absolute increase of ≥5 mm. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

  47. Best Overall Tumor Response Based on BICR Assessments in Part 2 [ Time Frame: Baseline, end of every two 21-day cycles, up until disease progression to a maximum of the time at least 70% OS events observed (a maximum of 4 years) ]
    Tumor response was assessed by CT or MRI. Overall visit response by RECIST v1.1 was determined by BICR. Tumor response data were used to determine each participant's time point response & BOR. CR was disappearance of all TLs, any pathological lymph nodes selected as TLs must have reduced in short axis to <10 mm. PR was at least a 30% decrease from baseline in the sum of diameters of TLs, as long as criteria for PD were not met. PD was a ≥20% increase in the smallest sum of diameters of TLs since treatment started (including baseline) and an absolute increase of ≥5 mm. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

  48. PFS Based on Assessments in Part 2 [ Time Frame: Baseline, end of every two 21-day cycles, up until disease progression to a maximum of the time at least 70% OS events observed (a maximum of 4 years) ]
    Tumor response was assessed by CT or MRI. PFS was defined as the time (months) from date of first dose date of study drug for participants in Part 1 until date of documented disease progression or death due to any cause, whichever occurred first. More specifically, PFS was determined using all the assessment data up until the last evaluable visit prior to or on the date of i) disease progression as defined by RECIST 1.1 or by clinical criteria as determined by the investigator; or ii) withdrawal of consent; or iii) receiving subsequent anticancer therapy, whichever was earlier. For PFS determined using response data derived programmatically, either clinical progression or progression by RECIST (whichever came first) was considered. Median and inter-quartile range of PFS were calculated using the Kaplan-Meier method.

  49. OS in Part 2 [ Time Frame: Baseline up until death or a maximum of the time at least 70% OS events observed (a maximum of 4 years) ]
    OS was calculated as the time (months) from date of first dose of study drug for participants in Part 2 to the date of death due to any cause. Participants who did not die during the study were censored at the date last known to be alive. Participants lacking data beyond the day of first dose of study drug had their survival time censored at day of first dose of study drug. OS was not censored if a participant received other anti-tumor treatments after the study drugs. Median and inter-quartile range of OS were calculated using the Kaplan-Meier method.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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

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
  • At least 1 target lesion that is unirradiated and measurable by RECIST, Version 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2
  • Adequate organ function

Exclusion Criteria:

  • Prior chemotherapy for extensive-stage SCLC
  • Presence of symptomatic 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 (the sites that are to be followed for determination of a response)
  • Receipt of any investigational medication within 4 weeks prior to enrollment

Information from the National Library of Medicine

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): NCT02499770


Locations
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Sponsors and Collaborators
G1 Therapeutics, Inc.
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 15, 2016
Statistical Analysis Plan  [PDF] February 14, 2018

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: G1 Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02499770    
Other Study ID Numbers: G1T28-02
2016-001583-11 ( EudraCT Number )
First Posted: July 16, 2015    Key Record Dates
Results First Posted: July 9, 2020
Last Update Posted: August 21, 2020
Last Verified: August 2020
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
CDK 4/6 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
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action