Back to resultsTrilaciclib Prior to Chemotherapy Plus Tislelizumab as 1L Treatment for Advanced Squamous Non-Small-Cell Lung Cancer
Primary Purpose
Advanced Squamous Non-Small-Cell Lung Cancer
Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Trilaciclib
Carboplatin
Paclitaxel
Tislelizumab
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Squamous Non-Small-Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria: 1. Age ≥ 18 years old and ≤ 75 years old, male or female; 2. Unresectable stage ⅢB and Ⅳ squamous non-small cell lung cancer confirmed by histology or cytology; 3. Have not received systemic anti-tumor therapy for advanced tumors in the past; 4. There is at least one measurable lesion that meets the RECIST1.1 criteria; 5. Patients with asymptomatic brain metastases or stable symptoms after treatment of brain metastases; 6. Laboratory tests meet the following criteria: Hemoglobin ≥ 100 G/L (female), 110 G/L (male) Neutrophil count ≥ 2 × 10^9/L Platelet count ≥ 100 × 10^9/L; Creatinine ≤ 15 mg/L or creatinine clearance (CrCl) ≥ 60 mL/min (Cockcroft-Gault formula); Total bilirubin ≤ 1.5 × upper limit of normal (ULN); ALT and AST ≤ 3 × ULN or ≤ 5 × ULN (for patients with liver metastases); Albumin ≥ 30g/L; 7.ECOG PS score 0-1; 8. Expected survival time ≥ 3 months; 9. Women: All women with potential fertility must have negative serum pregnancy test results during the screening period, and must take reliable contraceptive measures from the signing of informed consent to 3 months after the last administration; 10. Understand and sign the informed consent form. Exclusion Criteria: 1. Patients with the following diseases: Known HIV infection, active hepatitis B (defined as HBV DNA positive) and hepatitis C (HCV RNA positive); Interstitial lung disease/lung inflammation; Active, suspected autoimmune disease requiring systemic treatment in the past 2 years; 2. Vaccination of live attenuated vaccine within 4 weeks before enrollment, or expected to require vaccination of live attenuated vaccine during the study period; 3. Uncontrolled ischemic heart disease or clinically significant congestive heart failure (NYHA class III or IV); 4. Stroke or cardiovascular and cerebrovascular events within 6 months before enrollment 5. QTcF > 480 msec at screening and > 500 msec for patients with ventricular pacemakers 6. Previous hematopoietic stem cell or bone marrow transplantation 7.Hypersensitivity to the study drug or its components; 8. Those who are not considered suitable to participate in the study by the investigator.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Experimental: Trilaciclib+Chemotherpy+Tislelizumab
Active Comparator: Chemotherpy+Tislelizumab
Arm Description
Participants received Trilaciclib (240mg/m2) in combination with Paclitaxel (175mg/m2), Cisplatin (AUC=5), and Tislelizumab (200mg) treatment, every 3 weeks for up to 4-6 cycles (Induction). Following induction, patients will receive trilaciclib with tislelizumab for every 3 weeks
Participants received Paclitaxel (175mg/m2), Cisplatin (AUC=5), and Tislelizumab (200mg) treatment, every 3 weeks for up to 4-6 cycles (Induction). Following induction, patients will receive tislelizumab for every 3 weeks until PD
Outcomes
Primary Outcome Measures
incidence of grade ≥3 Neutrophil count decreased
The " incidence " is defined as the proportion of subjects from randomization to 15 days after the end of first-line chemotherapy treatment in which the events occurred. The occurrence of Grade 3 Neutrophil count decreased was a binary variable. If a patient had at least 1 absolute neutrophil count value <1 × 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
1. incidence of other indicators of Myelosuppression(Grade 4 Neutrophil count decreased, grade 3 or 4 thrombocytopenia, grade 3 or 4 anemia, febrile neutropenia)
The criterion for identifying any indicator of myelosuppression was if the preferred term for an adverse event was "event" according CTCAE 5.0 criteria. Any occurrence of an event during the induction treatment period is defined as a binary variable (Yes or No); Yes if total number of events ≥ 1 is observed, No for other scenarios. Each event with a unique start date during the induction treatment period was defined as a separate event
Usage rate of Supportive Intervention(Granulocyte colony-stimulating factor (G-CSF), platelet transfusion, red blood cell transfusion (week 5 and later), erythropoietin (ESA), iron, recombinant human interleukin-11, and/or thrombopoietin (TPO))
Any occurrence of the event during the induction treatment period was defined as a binary variable (Yes or No); Yes if total number of the event ≥ 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 event with a unique start date during the induction treatment period was defined as a separate event.
Progress free survival (PFS)
PFS defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause.
Overall Survival (OS)
OS is defined as the time until death due to any cause.
Objective Response Rate (ORR)
ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.prior to progression or any further therapy.
Disease Control Rate (DCR)
Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.
Duration of Response (DOR)
DOR was defined as the time from first documented evidence of CR or PR until disease progression as assessed by RECIST 1.1 or death.
Full Information
NCT ID
NCT05900921
First Posted
June 1, 2023
Last Updated
June 11, 2023
Sponsor
Sichuan University
Collaborators
Chengdu First people's hospital, Chengdu Second people's hospital, Chengdu Seventh People's Hospital, Mianyang Central Hospital, Shanxi Provincial Cancer Hospital, Shandong Provincial Cancer Hospital, Heilongjiang Provincial Cancer Hospital, Enshi Central Hospital, Neijiang Hospital of Traditional Chinese Medicine
1. Study Identification
Unique Protocol Identification Number
NCT05900921
Brief Title
Trilaciclib Prior to Chemotherapy Plus Tislelizumab as 1L Treatment for Advanced Squamous Non-Small-Cell Lung Cancer
Official Title
A Phase II, Randomized, Open-label Trial of Trilaciclib Prior to Chemotherapy Plus Tislelizumab as First-line Treatment for Advanced Squamous Non-Small-Cell Lung Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 1, 2023 (Anticipated)
Primary Completion Date
October 31, 2024 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sichuan University
Collaborators
Chengdu First people's hospital, Chengdu Second people's hospital, Chengdu Seventh People's Hospital, Mianyang Central Hospital, Shanxi Provincial Cancer Hospital, Shandong Provincial Cancer Hospital, Heilongjiang Provincial Cancer Hospital, Enshi Central Hospital, Neijiang Hospital of Traditional Chinese Medicine
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The purpose of this study is to explore the myeloprotective effects of trilaciclib in advanced squamous non-small cell lung cancer patients receiving a combination therapy of chemotherapy(carboplatin+paclitaxel) and immune checkpoint inhibitor (tislelizumab), as well as enhancing antitumor efficacy and possible immunological synergies.
Detailed Description
This is a phase 2 clinical trial that is randomized, controlled, multicenter, and prospective in design. A total of 132 patients with advanced, untreated squamous non-small cell lung cancer will be randomly assigned 1:1 to receive or not receive Trilaciclib (240mg/m2) in combination with Paclitaxel (175mg/m2), Cisplatin (AUC=5), and Tislelizumab (200mg) treatment, every 3 weeks for up to 4-6 cycles (Induction). Following induction, patients will receive or not receive trilaciclib with tislelizumab for every 3 weeks until PD, intolerable toxicity, withdrawal, or death. If subsequent chemotherapy is indicated for patients after first-line progression, trilaciclib will be provided to observe the myeloprotective effect in second-line treatment. The study is expected to commence recruitment in mainland China in about May 2023. It is expected that the trial will end in December 2025.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Squamous Non-Small-Cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
132 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Experimental: Trilaciclib+Chemotherpy+Tislelizumab
Arm Type
Experimental
Arm Description
Participants received Trilaciclib (240mg/m2) in combination with Paclitaxel (175mg/m2), Cisplatin (AUC=5), and Tislelizumab (200mg) treatment, every 3 weeks for up to 4-6 cycles (Induction).
Following induction, patients will receive trilaciclib with tislelizumab for every 3 weeks
Arm Title
Active Comparator: Chemotherpy+Tislelizumab
Arm Type
Active Comparator
Arm Description
Participants received Paclitaxel (175mg/m2), Cisplatin (AUC=5), and Tislelizumab (200mg) treatment, every 3 weeks for up to 4-6 cycles (Induction).
Following induction, patients will receive tislelizumab for every 3 weeks until PD
Intervention Type
Drug
Intervention Name(s)
Trilaciclib
Intervention Description
IV infusion, d1
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
IV infusion, d1
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
IV infusion, d1
Intervention Type
Drug
Intervention Name(s)
Tislelizumab
Intervention Description
IV infusion, d1
Primary Outcome Measure Information:
Title
incidence of grade ≥3 Neutrophil count decreased
Description
The " incidence " is defined as the proportion of subjects from randomization to 15 days after the end of first-line chemotherapy treatment in which the events occurred. The occurrence of Grade 3 Neutrophil count decreased was a binary variable. If a patient had at least 1 absolute neutrophil count value <1 × 10^9/L during the Induction Period, the patient was assigned as Yes to the occurrence of SN; otherwise, it was No.
Time Frame
Induction Period，From date of randomization, 21 day treatment cycles up to a maximum of 4-6 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator
Secondary Outcome Measure Information:
Title
1. incidence of other indicators of Myelosuppression(Grade 4 Neutrophil count decreased, grade 3 or 4 thrombocytopenia, grade 3 or 4 anemia, febrile neutropenia)
Description
The criterion for identifying any indicator of myelosuppression was if the preferred term for an adverse event was "event" according CTCAE 5.0 criteria. Any occurrence of an event during the induction treatment period is defined as a binary variable (Yes or No); Yes if total number of events ≥ 1 is observed, No for other scenarios. Each event with a unique start date during the induction treatment period was defined as a separate event
Time Frame
Induction Period，From date of randomization, 21 day treatment cycles up to a maximum of 4-6 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator
Title
Usage rate of Supportive Intervention(Granulocyte colony-stimulating factor (G-CSF), platelet transfusion, red blood cell transfusion (week 5 and later), erythropoietin (ESA), iron, recombinant human interleukin-11, and/or thrombopoietin (TPO))
Description
Any occurrence of the event during the induction treatment period was defined as a binary variable (Yes or No); Yes if total number of the event ≥ 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 event with a unique start date during the induction treatment period was defined as a separate event.
Time Frame
Induction Period，From date of randomization, 21 day treatment cycles up to a maximum of 4-6 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator
Title
Progress free survival (PFS)
Description
PFS defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause.
Time Frame
untill Progressive Disease(PD) or death(up to 24 months)
Title
Overall Survival (OS)
Description
OS is defined as the time until death due to any cause.
Time Frame
From randomization until death (up to 24 months)
Title
Objective Response Rate (ORR)
Description
ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.prior to progression or any further therapy.
Time Frame
each 42 days up to intolerance the toxicity or PD (up to 24 months)
Title
Disease Control Rate (DCR)
Description
Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.
Time Frame
each 42 days up to intolerance the toxicity or PD (up to 24 months)
Title
Duration of Response (DOR)
Description
DOR was defined as the time from first documented evidence of CR or PR until disease progression as assessed by RECIST 1.1 or death.
Time Frame
Up to approximately 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
1. Age ≥ 18 years old and ≤ 75 years old, male or female;
2. Unresectable stage ⅢB and Ⅳ squamous non-small cell lung cancer confirmed by histology or cytology;
3. Have not received systemic anti-tumor therapy for advanced tumors in the past;
4. There is at least one measurable lesion that meets the RECIST1.1 criteria;
5. Patients with asymptomatic brain metastases or stable symptoms after treatment of brain metastases;
6. Laboratory tests meet the following criteria: Hemoglobin ≥ 100 G/L (female), 110 G/L (male) Neutrophil count ≥ 2 × 10^9/L Platelet count ≥ 100 × 10^9/L; Creatinine ≤ 15 mg/L or creatinine clearance (CrCl) ≥ 60 mL/min (Cockcroft-Gault formula); Total bilirubin ≤ 1.5 × upper limit of normal (ULN); ALT and AST ≤ 3 × ULN or ≤ 5 × ULN (for patients with liver metastases); Albumin ≥ 30g/L;
7.ECOG PS score 0-1;
8. Expected survival time ≥ 3 months;
9. Women: All women with potential fertility must have negative serum pregnancy test results during the screening period, and must take reliable contraceptive measures from the signing of informed consent to 3 months after the last administration;
10. Understand and sign the informed consent form.
Exclusion Criteria:
1. Patients with the following diseases: Known HIV infection, active hepatitis B (defined as HBV DNA positive) and hepatitis C (HCV RNA positive); Interstitial lung disease/lung inflammation; Active, suspected autoimmune disease requiring systemic treatment in the past 2 years;
2. Vaccination of live attenuated vaccine within 4 weeks before enrollment, or expected to require vaccination of live attenuated vaccine during the study period;
3. Uncontrolled ischemic heart disease or clinically significant congestive heart failure (NYHA class III or IV);
4. Stroke or cardiovascular and cerebrovascular events within 6 months before enrollment 5. QTcF > 480 msec at screening and > 500 msec for patients with ventricular pacemakers
6. Previous hematopoietic stem cell or bone marrow transplantation
7.Hypersensitivity to the study drug or its components;
8. Those who are not considered suitable to participate in the study by the investigator.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yongsheng Wang, professor
Phone
+86 028-85429455
Email
wangys@scu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yongsheng Wang
Organizational Affiliation
West China Hospital
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Trilaciclib Prior to Chemotherapy Plus Tislelizumab as 1L Treatment for Advanced Squamous Non-Small-Cell Lung Cancer
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