Myelosuppression
Conditions
Keywords
LS-SCLC, small cell lung cancer, Myelosuppression, Trilaciclib
Brief summary
The primary goal of this study is to evaluate the myelo-protective effect and safety of Trilaciclib in participants with limited stage small cell lung cancer (LS-SCLC) who are receiving concurrent chemo-radiotherapy. Researchers will compare Trilaciclib with placebo (a look-alike substance that contains no drug) to see if Trilaciclib works better in protecting the participant's marrow function while receiving concurrent chemo-radiotherapy.
Detailed description
The study will enroll approximately 106 participants with LS-CLC. The participants will be randomly assigned in a 1:1 ratio to two groups. One group will receive treatment with Trilaciclib + concurrent chemo-radiotherapy. The other group will receive placebo + concurrent chemo-radiotherapy. Participants will receive the investigational drug until completion of 4 cycles of Trilaciclib +chemotherapy and concurrent radiotherapy, occurrence of radiographic disease progression, intolerable toxicity, investigator-assessed lack of clinical benefit, voluntary withdrawal from study treatment by the participant or their legally authorized representative, pregnancy, lost to follow-up, death, or study termination, whichever occurs first. The study process includes screening period, treatment period, end-of-treatment visit, safety follow-up visit, and end-of-study visit.
Interventions
DRUGTrilaciclib
Trilaciclib at 240mg/m\^2;
OTHERTrilaciclib Placebo
250 mL of 5% dextrose in water or normal saline (0.9% sodium chloride solution)
Etoposide Injection at dose level of 100 mg/m\^2
DRUGCarboplatin or Cisplatin Injection
Use Calvert formula to calculate Carboplatin dosage (AUC=5 mg/mL/min,750 mg at most）; Cisplatin at a dose level of 75 mg/m\^2.
RADIATIONRadiotherapy
30-33 days of totally 60-66 Gy for QD radiation, or 15 days of totally 45 Gy for BID radiation.
Sponsors
Jiangsu Simcere Pharmaceutical Co., Ltd.
Simcere Zaiming Pharmaceutical Co., Ltd .
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Histologically and/or cytologically confirmed small cell lung cancer (SCLC) with clinical staging confirming limited-stage disease and no evidence of distant metastasis； * 2\. Fit for concurrent chemo-radiotherapy； * 3\. Adverse reactions related to prior anti-tumor surgery have fully recovered； * 4\. Has at least one measurable lesion per RECIST 1.1 that has not been previously irradiated； * 5\. Eastern Cooperative Oncology Group （ECOG）performance status of 0 or 1; * 6\. Has adequate organ and bone marrow function, without receipt of hematopoietic growth factors, blood transfusions, or platelet transfusions within 14 days prior to the first dose of study drug；
Exclusion criteria
* 1\. Extensive-stage small cell lung cancer * 2\. mixed-type small cell lung cancer, and transformed small cell lung cancer； * 3\. Has received prior anti-tumor therapy for small cell lung cancer, including radiotherapy, chemotherapy, or immunotherapy； * 4\. Has known allergy to any study drug or its components, or has any contraindication to any study drug. * 5\. Has any active infections requiring for intravenous treatment within 14 days prior to the first dose of study treatment； * 6\. Has received any live vaccine within 28 days prior to the first dose of study drug. * 7\. Has received any major surgeries within 28 days prior to the first dose of study treatment or expects to receive major surgeries during the study; * 8\. History of another active malignancy within the past 5 years, except for localized cancers that have been cured and are considered by the investigator to be at low risk of recurrence, including basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast. * 9\. With a history of active tuberculosis infection within 1 year; trial participants with a history of active tuberculosis may be eligible for enrollment if, in the investigator's judgment, there has been no evidence of active tuberculosis for more than 1 year prior to the first dose. * 10\. Active or chronic hepatitis B or hepatitis C infection; * 11\. Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). * 12\. With clinically significant cardiovascular disease within 6 months prior to the first dose * 13\. History of interstitial lung disease/non-infectious pneumonitis requiring steroid treatment, or current interstitial lung disease/non-infectious pneumonitis requiring steroid treatment; * 14\. Prior allogeneic or autologous hematopoietic stem cell transplantation or history of graft-versus-host disease; * 15\. Pregnant or breastfeeding female trial participants, or female trial participants of childbearing potential. Female participants of childbearing potential may be enrolled if they have a negative blood pregnancy test within 7 days prior to the first dose and agree to use effective contraception from the time of signing the informed consent form until 6 months after the last dose of study medication or the last radiotherapy, whichever is longer. * 16\. Any other conditions that, in the investigator's opinion, make the participant unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The duration of severe neutropenia (DSN) in cycle 1 | During the first cycle (each cycle is 21 days) | The time duration of absolute neutrophil count (ANC) decrease meeting Grade 4 per NCI CTCAE 5.0 (i.e., ANC \< 0.5 × 10⁹/L). |
| The incidence of severe neutropenia (SN) | From the time of first dosing until 30 days after the end of study treatment, up to about 3.5 months | The incidence of absolute neutrophil count (ANC) decrease meeting Grade 4 per NCI CTCAE 5.0 (i.e., ANC \< 0.5 × 10⁹/L). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Granulocyte colony-stimulating factor (G-CSF) utilization rate | From the time of first dosing until 30 days after the end of study treatment, up to about 3.5 months | — |
| Incidence of febrile neutropenia | From the time of first dosing until 30 days after the end of study treatment, up to about 3.5 months | — |
| The lowest absolute neutrophil count in each cycle | From the time of first dosing until 30 days after the end of study treatment, up to about 3.5 months] | — |
| Incidence of grade ≥3 hemoglobin decrease | From the time of first dosing until 30 days after the end of study treatment, up to about 3.5 month | — |
| Incidence of red blood cell transfusions (from Week 5 onward) | From Week 5 until 30 days after the end of study treatment, up to about 3 months | — |
| Erythropoiesis-stimulating agent (ESA) utilization rate | From the time of first dosing until 30 days after the end of study treatment, up to about 3.5 months | — |
| Incidence of grade ≥3 platelet count decrease | From the time of first dosing until 30 days after the end of study treatment, up to about 3.5 months | — |
| Incidence of platelet transfusions | From the time of first dosing until 30 days after the end of study treatment, up to about 3.5 months. | — |
| Rate of thrombopoiesis-stimulating agent use. | From the time of first dosing until 30 days after the end of study treatment, up to about 3.5 months | — |
| Incidence of grade 3 and 4 hematologic toxicities | From the time of first dosing until 30 days after the end of study treatment, up to about 3.5 months | — |
| Changes over time in absolute neutrophil count, platelet count, absolute lymphocyte count, and hemoglobin | From the time of first dosing until 30 days after the end of study treatment, up to about 3.5 months | — |
| Composite endpoint: Incidence of important hematologic adverse events. | From the time of first dosing until 30 days after the end of study treatment, up to about 3.5 months | The proportion of patients who experience any of the following: hematologic adverse event that leads to hospitalization or prolongation of hospitalization, dose adjustment of chemotherapy, febrile neutropenia, prolongation of severe neutropenia(SN) (more than 5 days),or red blood cell (RBC) transfusions administered at or after Week 5. |
Countries
China
Outcome results
None listed