SCLC, Extensive Stage
Conditions
Keywords
ES-SCLC
Brief summary
This study hypothesizes that nanocrystalline megestrol acetate can improve the cachexia condition in patients and enhance the efficacy of immunochemotherapy regimens. It plans to enroll patients newly diagnosed with extensive-stage small-cell lung cancer (ES-SCLC) who are in the pre-cachexia or cachexia stage of the cachexia trajectory. These patients will receive first-line standard immunochemotherapy combined with nanocrystalline megestrol acetate intervention. Compared to the use of the first-line standard immunochemotherapy regimen alone, the study will monitor changes in body weight and body composition, which are nutritional status indicators relative to baseline, to assess whether these changes can translate into improved survival benefits and enhanced quality of life for patients. The objective of this clinical study are：1.To assess the change in body weight relative to baseline in malignant patients with ES-SCLC treated with a first-line standard immunochemotherapy regimen during treatment with a simultaneous co-administration of nanocrystalline megestrol supportive intervention, compared to standard treatment. 2.To assess the impact of simultaneous co-administration of nanocrystalline megestrol supportive intervention during treatment with a first-line standard immunochemotherapy regimen, compared to standard treatment, on survival benefit and quality of life in patients with ES-SCLC malignancy. 3.To explore the improvement in inflammatory and nutritional markers and changes in lymphocyte subpopulations in patients with ES-SCLC malignant disease with simultaneous co-administration of nanocrystalline megestrol supportive intervention during treatment with a first-line standard immunochemotherapy regimen, compared to standard treatment.
Detailed description
This study employed a Phase II adaptive umbrella trial , aiming to enrich patients with ES - SCLC in the pre - cachexia or cachexia stage and provide them with the opportunity to receive potentially effective megestrol acetate treatment. To expand the scope of patients receiving treatment and enhance the understanding of the benefit - risk profile in a broader population, we established two cohorts: the criteria - fulfilled (CF) cohort, where patients need to meet all inclusion and exclusion criteria; and the compassionate use (CU) cohort, where patients meet the inclusion criteria and major exclusion criteria but may not meet the minor exclusion criteria. Concurrently, a prospective real - world study (RWS) was initiated to observe the clinical outcomes of patients in the pre - cachexia/cachexia stage receiving physician - selected treatment (PTOC). The CF cohort plans to enroll 200 subjects, with liver metastasis (yes vs no), cachexia stage (pre - cachexia vs cachexia), and ECOG PS (0 - 1 vs 2) as stratification factors. These subjects will be randomly assigned to 2 treatment groups at a 1:1 ratio: 1. Nano - Megestrol Group: Nanocrystalline megestrol (QD, up to 12 weeks) + tislelizumab (Q3W, 4 cycles) + chemotherapy (carboplatin + etoposide, Q3W, 4 cycles); 2. Standard Control Group: Tislelizumab (Q3W, 4 cycles) + chemotherapy (carboplatin + etoposide, Q3W, 4 cycles). In the CU cohort, the treatment plan and visits are consistent with the nanocrystalline megestrol group in the criteria - fulfilled (CF) cohort.In the RWS cohort, immunotherapy can use PD - 1/PD - L1 inhibitors other than tislelizumab, and other drugs are consistent with the nanocrystalline megestrol group in the criteria - fulfilled (CF) cohort. CU and RWS groups do not set a specific number of subjects to be enrolled.
Interventions
Nanocrystalline Megestrol Acetate + Tislelizumab+ Chemotherapy (Carboplatin + Etoposide)
DRUGTislelizumab
Tislelizumab combined with chemotherapy (Carboplatin + Etoposide)
DRUGPTOC
Nanocrystalline Megestrol Acetate+PD-(L)1 inhibitors+chemotherapy
Sponsors
Henan Cancer Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Good compliance and voluntary signing of a written informed consent form (ICF). 2. Age at enrolment ≥18 years, ≤75 years, and gender-neutral (patients \>75 years old will be enrolled in the RWS cohort). 3. Eastern Cooperative Oncology Group (ECOG) physical status score of 0-2 (patients with PS 3 and above due to oncological factors can be enrolled in the CU cohort or RWS cohort). 4. Expected survival ≥ 6 months. 5. Patients with histologically or cytologically confirmed small cell lung cancer (SCLC) and confirmed extensive stage small cell lung cancer based on AJCC 8th edition staging or the American Legion Lung Cancer Association (VALG) Stage II staging method (excluding mixed small cell lung cancer). 6. Subjects have not received prior systemic systemic chemotherapy for metastatic disease. Subjects with prior adjuvant/neoadjuvant chemotherapy or radical synchronous or sequential radiotherapy for non-metastatic disease with curative intent are eligible for this study if disease progression occurred \>6 months after the end of the last treatment. 7. Have at least one measurable tumour lesion according to RECIST v1.1. 8. Meet the diagnostic criteria for premalignant or malignant stage. Diagnostic criteria for pre-Cachexia stage Referring to the 2016 ESPEN consensus on terminology, the following conditions are also met: * Maximum weight loss \<5% relative to baseline 6 months ago; * Anorexia (presence of anorexia complaints or anorexia/malignant condition subscale FAACT-A/CS score ≤37); (iii) Serum C-reactive protein CRP ≥ 5 mg/L. Diagnostic criteria for cachexia Any one of the following conditions combined with loss of appetite or systemic inflammatory response. Involuntary weight loss \>5% in the last 6 months. ② Weight loss \>2% when BMI \<18.5kg ③ Weight loss \>2% with muscle loss. 9. Determine good organ function by the following requirements: a) Routine haematology (no supportive therapy with any blood components and cell growth factors within 7 days prior to initiation of study treatment): i. Absolute neutrophil ANC ≥ 1.5 × 10\^9/L (1,500/mm3); ii. Platelet count ≥ 100 × 10\^9/L (100,000/mm3); and iii. Haemoglobin ≥ 90 g/L. b) Renal function: i. Creatinine clearance\* (CrCl) calculated ≥ 50 mL/min \* The Cockcroft-Gault formula will be used to calculate CrCl (Cockcroft-Gault formula) CrCl (mL/min) = (140 - age) × weight (kg) × F}/ (SCr (mg/dL) × 72) F = 1 for males; F = 0.85 for females; SCr = serum creatinine. ii. urine protein ≤ 1+ or 24-hour (h) urine protein quantitatively \< 1.0 g. c) Liver function: i. serum total bilirubin (TBil) ≤ 1.5 × upper limit of normal (ULN); TBil ≤ 3 × ULN for patients with liver metastases or evidence of confirmed/suspected Gilbert's disease. ii. AST and ALT ≤ 2.5 × ULN; for patients with liver metastases, AST and ALT ≤ 5 × ULN iii. serum albumin (ALB) ≥ 28 g/L d) Coagulation: International Normalised Ratio and Activated Partial Thromboplastin Time ≤ 1.5 × ULN (unless the patient is on anticoagulant therapy and the coagulation parameters (PT/INR and APTT) are in the expected range for treatment with anticoagulants at screening). e) Cardiac function: left ventricular ejection fraction (LVEF) ≥50%. 10. Lung function indices 1st second forced expiratory volume (FEV1) \>1L or \>30% of predicted value, and lung carbon monoxide diffusion function (DLCO) \>30% of predicted value; 11. Female patients of childbearing potential must have a urine or serum pregnancy test (if the urine pregnancy test result is not confirmed negative, a serum pregnancy test is required, and the serum pregnancy result will be used as the basis for the negative result) performed within 3 days prior to the first dose of the drug, and the result is negative. If a female patient of childbearing potential engages in sexual intercourse with an unsterilised male partner, the patient must be using an acceptable method of contraception from the start of screening and must agree to continue to use the adopted method of contraception for a period of 120 days after the last dose of study drug; the decision on whether or not to discontinue contraception after this time point should be discussed with the investigator. If an unsterilised male patient has sexual intercourse with a female partner of childbearing potential, the patient must use an effective method of contraception from the start of screening until the 120th day after the last dose of study medication; discontinuation of contraception after this time point should be discussed with the investigator. 12. The patient is willing and able to comply with the schedule of visits, treatment regimens, laboratory tests, and other requirements of the study.
Exclusion criteria
Subjects meeting any of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The proportion of weight increase relative to baseline > 5% (Week 12) | after 12 weeks of treatment | The proportion of weight increase relative to baseline \> 5% (Week 12) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | From date of randomization until the date of first documented date of death from any cause, assessed up to 60 months | Proportion of patients with reduction in stable in tumor burden of a predefined amount，Baseline until partial response (PR) or complete response (CR), whichever occurs first，assessed up to 12 months |
| Progression Free Survival (PFS) | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months | Time from random to either radiological progression or death |
| overall survival (OS ) | From date of randomization until the date of first documented date of death from any cause, assessed up to 60 months | Time from the first treatment to death from any cause or the end of the study |
Countries
China
Contacts
Primary ContactQiming Wang
Backup ContactShuxiang Ma
Outcome results
None listed