Cachexia-Anorexia Syndrome, Lung Cancer
Conditions
Brief summary
Patients with advanced lung cancer are a high-risk population for cancer-related anorexia-cachexia syndrome (CACS). Meanwhile, the adverse reactions of chemotherapy and immunotherapy potentially exacerbate the occurrence and progression of CACS. CACS seriously affects the quality of life of patients with advanced lung cancer, significantly shortens the overall survival (OS) and progression-free survival (PFS), forming a vicious cycle. A number of previous studies have shown that combined supportive therapies such as megestrol acetate during chemotherapy or concurrent chemoradiotherapy for advanced tumor patients is a clinically meaningful and feasible treatment model in clinical practice. However, the efficacy and optimal treatment timing of combination with current first-line immunochemotherapy regimens remain unclear. Although mechanistic studies have shown that anti-cachexia therapy may synergistically enhance the efficacy of immunotherapy, relevant clinical research evidence is lacking. Therefore, this study hypothesizes that the combination of first-line immunochemotherapy regimen and nano-crystalline megestrol acetate can improve the clinical benefits of patients with advanced lung cancer. It is planned to enroll patients with advanced lung cancer who present with anorexia-cachexia, and administer nano-crystalline megestrol acetate intervention (nano-crystalline megestrol acetate or its placebo control) during first-line immunochemotherapy. The changes in body weight relative to the baseline, as well as the impact on survival benefits and quality of life of patients, will be detected. In China, megestrol acetate is mainly available in two dosage forms: oral suspension and dispersible tablets. The oral suspension of megestrol acetate adopts nano-crystal technology (referred to as nano-crystalline megestrol acetate), which reduces the particle size of megestrol acetate and improves bioavailability. Previous randomized controlled studies have shown that it is superior to non-nano-crystal dosage forms in improving body weight.
Interventions
Nano-crystalline Megestrol Acetate+PD-(L)1 inhibitor (Q3W, until PD) + chemotherapy (based on guidelines)
OTHERNano-crystalline Megestrol Acetate Oral Suspension placebo
Nano-crystalline Megestrol Acetate placebo+PD-(L)1 inhibitor (Q3W, until PD) + chemotherapy (based on guidelines)
Sponsors
Guangzhou Institute of Respiratory Disease
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Patients must meet all the following criteria to be eligible for study enrollment: 1. Inclusion criteria for advanced lung cancer: 1. Patients with histologically or cytologically confirmed locally advanced (Stage ⅢC) or metastatic (Stage IV) non-small cell lung cancer (NSCLC) that cannot be completely resected surgically or treated with radical chemoradiotherapy, according to the 8th edition of the TNM staging classification for lung cancer by the International Association for the Study of Lung Cancer and the American Joint Committee on Cancer Classification. 2. Patients with histologically or cytologically confirmed small cell lung cancer (SCLC) and diagnosed as extensive-stage SCLC based on the 8th edition of AJCC staging or the Veterans Administration Lung Group (VALG) criteria (excluding mixed small cell lung cancer). 3. Subjects who have not received prior systemic chemotherapy for metastatic disease. Subjects who received adjuvant/neoadjuvant chemotherapy or radical concurrent/sequential chemoradiotherapy with curative intent for non-metastatic disease are eligible if disease progression occurs \>6 months after the end of the last treatment. 4. At least one measurable tumor lesion according to RECIST v1.1. 2. Criteria for pre-cachexia or cachexia stage: 1. Pre-cachexia diagnostic criteria (all three must be met): * Unintentional weight loss ≤5% in the past 6 months; ② Systemic inflammation (CRP \>5 mg/L); ③ Decreased appetite (FAACT-A/CS 12 score ≤37). 2. Fearon diagnostic criteria for cachexia stage (any one of the following combined with decreased appetite \[FAACT-A/CS 12 score ≤37\] or systemic inflammation \[CRP \>5 mg/L\]): * Unintentional weight loss \>5% in the past 6 months; ② Weight loss \>2% when BMI \<18.5 kg/m². 3. General inclusion requirements: 1. Good compliance and signed informed consent form. 2. Age 18-75 years, regardless of gender. 3. ECOG performance status 0-2. 4. Life expectancy ≥6 months. 5. Good organ function: • Hematological: Neutrophils ≥1.5×10⁹/L, hemoglobin ≥9 g/dL, platelets ≥100×10⁹/L. • Liver function: Bilirubin ≤1.5×ULN (patients with known Gilbert disease and serum bilirubin ≤3×ULN are eligible); AST and ALT ≤2.5×ULN (if liver metastasis is present, AST and ALT ≤5×ULN); alkaline phosphatase ≤3×ULN (if liver or bone metastasis is present, ALP ≤5×ULN); albumin ≥3 g/dL. * Coagulation function: International normalized ratio (INR), prothrombin time (PT), or activated partial thromboplastin time (aPTT) ≤1.5×ULN. * Renal function: Creatinine clearance rate ≥60 mL/min (calculated by Cockcroft-Gault formula). * Urine protein ≤1+ or 24-hour urine protein \<1.0 g. * Cardiac function: Left ventricular ejection fraction (LVEF) ≥50%. 6. Female patients of childbearing potential must have a negative urine or serum pregnancy test within 3 days before the first drug administration (if the urine test is inconclusive, a serum test is required, with the serum result as the standard). If a female patient of childbearing potential has sexual activity with an unsterilized male partner, she must use an acceptable contraceptive method from screening and agree to continue contraception for 120 days after the last administration of the study drug. Whether to discontinue contraception after this period should be discussed with the investigator. Male patients who are not sterilized and have sexual activity with female partners of childbearing potential must use effective contraception from screening to 120 days after the last administration. Whether to discontinue contraception after this period should be discussed with the investigator.
Exclusion criteria
* (1) Cancer-specific
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of participants with a body weight increase of >5% relative to the baseline. | From enrollment to the end of treatment at 12 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| QOL | From enrollment to the end of treatment at 12 week | Participants report a score on a scale EORTC QLQ-C30. |
| Anxiety and depression | From enrollment to the end of treatment at 12 week | Participants report a score on a scale HADS |
| PFS in 6 months and 12 months | From enrollment to the end of treatment at 6 months and 12 months | — |
| Treatment compliance ( relative dose intensity, RDI) | From enrollment to the end of treatment at 12 weeks | Relative Dose Intensity (RDI): The ratio of the actual administered dose intensity to the standard planned dose intensity, usually expressed as a percentage (%). |
| appetite | From enrollment to the end of treatment at 12 week | The proportion of participants with a better appetite \>5% relative to the baseline. Participants report a score on a scale FAACT-A/CS 12，with 4 higher scores mean a better outcome. |
| Inflammatory indicators (CRP, IL-1, IL-6, TNF-α, etc.) | From enrollment to the end of treatment at 12 weeks | — |
| Nutritional indicators (prealbumin, albumin, hemoglobin) | From enrollment to the end of treatment at 12 weeks | — |
| ACTH、VIP、SSTR | From enrollment to the end of treatment at 12 weeks | — |
| L3-SMI | From enrollment to the end of treatment at 12 weeks | The Hounsfield unit (HU) limits used for assessing skeletal muscle mass ranged from -29 to +150 HU. The muscle area was normalised for height, resulting in a ratio (cm2/m2) known as the L3 skeletal mass index (L3 SMI). |
Contacts
Primary Contactxiaohong xie
Outcome results
None listed