Nanocrystalline Megestrol + Immunochemo As 1st-Line for ES-SCLC Cachexia

NCT06793228 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 2024-542
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 4

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.

Conditions

SCLC, Extensive Stage

Keywords

ES-SCLC

Outcome Measures

Primary Outcomes (1)

• The proportion of weight increase relative to baseline > 5% (Week 12)

  The proportion of weight increase relative to baseline \> 5% (Week 12)

  after 12 weeks of treatment

Secondary Outcomes (3)

• Objective Response Rate

  From date of randomization until the date of first documented date of death from any cause, assessed up to 60 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

• overall survival (OS )

  From date of randomization until the date of first documented date of death from any cause, assessed up to 60 months

Study Arms (4)

criteria-fulfilled (CF) cohort

EXPERIMENTAL

Patients must meet all inclusion and exclusion criteria. Erolled patients will be randomly assigned to receive Nanocrystalline Megestrol Acetate (5ml once a day, up to 12 weeks) +Tislelizumab (200mg on day 1, once every 3 weeks) combined with chemotherapy (Carboplatin, AUC=5 on day 1+ Etoposide, 100mg/m2 on day 1 to day 3, once every 3 weeks). Megestrol will be discontinued after the completion of 4 cycles. Tislelizumab 200 mg will be used as maintenance therapy, repeated every 3 weeks until disease progression or intolerable toxicity.

Drug: Tislelizumab

Criteria-fulfilled(CF) cohort

ACTIVE COMPARATOR

Patients must meet all inclusion and exclusion criteria. Erolled patients will be randomly assigned to receive Tislelizumab (200mg on day 1, once every 3 weeks) combined with chemotherapy (Carboplatin, AUC=5 on day 1+ Etoposide, 100mg/m2 on day 1 to day 3, once every 3 weeks). After 4 cycles of treatment, Tislelizumab 200 mg will be used as maintenance therapy, repeated every 3 weeks until disease progression or intolerable toxicity.

Drug: Nanocrystalline Megestrol Acetate

compassionate use (CU) cohort

OTHER

Patients meet the inclusion criteria and main exclusion criteria, but may not meet the secondary exclusion criteria. Erolled patients will receive Nanocrystalline Megestrol Acetate (5ml once a day, up to 12 weeks) +Tislelizumab (200mg on day 1, once every 3 weeks) combined with chemotherapy (Carboplatin, AUC=5 on day 1+ Etoposide, 100mg/m2 on day 1 to day 3, once every 3 weeks). Megestrol will be discontinued after the completion of 4 cycles. Tislelizumab 200 mg will be used as maintenance therapy, repeated every 3 weeks until disease progression or intolerable toxicity.

Drug: Nanocrystalline Megestrol Acetate

prospective real-world study (RWS) cohort

OTHER

Observe the clinical outcomes of ES-SCLC patients with pre-cachexia/cachexia receiving physician-targeted treatment (PTOC). Patients diagnozed with ES-SCLC, complicated pre-cachexia/cachexia, and are scheduled to receive chemo-immunotherapy will be included in this cohort. Erolled patients will receive Nanocrystalline Megestrol Acetate (5ml once a day, up to 12 weeks) + PD-1/L1 inhibitors + chemotherapy (Carboplatin, AUC=5 on day 1+ Etoposide, 100mg/m2 on day 1 to day 3, once every 3 weeks). Megestrol will be discontinued after the completion of 4 cycles. PD-1/L1 inhibitors will be used as maintenance therapy, repeated every 3 weeks until disease progression or intolerable toxicity.

Drug: PTOC

Interventions

Nanocrystalline Megestrol Acetate DRUG

Nanocrystalline Megestrol Acetate + Tislelizumab+ Chemotherapy (Carboplatin + Etoposide)

Criteria-fulfilled(CF) cohort; compassionate use (CU) cohort

Tislelizumab DRUG

Tislelizumab combined with chemotherapy (Carboplatin + Etoposide)

criteria-fulfilled (CF) cohort

PTOC DRUG

Nanocrystalline Megestrol Acetate+PD-(L)1 inhibitors+chemotherapy

prospective real-world study (RWS) cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Good compliance and voluntary signing of a written informed consent form (ICF).
• Age at enrolment ≥18 years, ≤75 years, and gender-neutral (patients \>75 years old will be enrolled in the RWS cohort).
• 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).
• Expected survival ≥ 6 months.
• 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).
• 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.
• Have at least one measurable tumour lesion according to RECIST v1.1.
• 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.
• 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

You may not qualify if:

• Presence of malignant conditions other than those caused by oncological etiology such as chronic respiratory failure requiring home oxygen support, chronic obstructive pulmonary disease, chronic and persistent congestive heart failure, acquired immunodeficiency syndrome, uncontrollable thyroid disease.
• Presence of any condition that interferes with gastrointestinal absorption such as dysphagia, malabsorption, previous history of gastrectomy, or uncontrollable vomiting; being on tube feeding or parenteral nutrition; presence of anorexia nervosa, anorexia due to psychiatric disorders, or pain that makes it difficult to eat.
• Being on other appetite or weight-increasing medications such as: adrenocortical steroids (except for short-term use of dexamethasone during chemotherapy), androgens, progesterone analogues, thalidomide, and anamorelin or other appetite stimulants.
• Use of any proprietary or herbal medicine used for cancer control within 14 days prior to the first dose of study drug.
• Pre-existing (within 3 years) or current other malignancies, except cured localised tumours (e.g. basal cell skin cancer, squamous cell skin cancer, superficial bladder cancer, cervical carcinoma in situ, etc.).
• Concurrent enrolment in another clinical study, unless it is an observational, non-interventional clinical study or a follow-up period of an interventional study.
• Previous treatment with any other antibody or drug specifically targeting the T-cell co-stimulatory or checkpoint pathway such as anti-PD-1, PD-L1 or CTLA-4 therapy.
• Presence of esophagogastric fundal varices, severe ulcers, history of gastrointestinal perforation and/or fistulae, history of gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), history of intra-abdominal abscess or acute gastrointestinal bleeding, thromboembolic disease, ascites, or lower extremity oedema in the 6 months prior to the first dose.
• Current uncontrolled co-morbidities including, but not limited to, decompensated cirrhosis, renal failure, uncontrolled metabolic disorders, severe active peptic ulcer disease or gastritis, or psychiatric/social conditions that would limit the patient's ability to comply with the requirements of the study or affect the patient's ability to provide written informed consent.
• Pre-existing history of myocarditis, cardiomyopathy, or malignant arrhythmia. Unstable angina requiring hospitalisation, myocardial infarction, congestive heart failure (aortic aneurysm of grade 2 and at risk of rupture as determined by the New York Heart Association functional class), or other cardiac impairment (e.g., poorly controlled arrhythmia, myocardial ischaemia) that may interfere with the evaluation of the safety of the investigational drug, within 6 months prior to the first dose of study drug.
• Severe chronic or active infection (including tuberculosis infection, etc.) requiring systemic antibacterial, antifungal, or antiviral therapy ≤ 14 days prior to the first dose of study drug.
• Patients with active molluscum contagiosum metastases, or brain metastases that are not well controlled; Patients with stable treated brain metastases may be enrolled at the discretion of the investigator; Patients with untreated, asymptomatic brain metastases may be enrolled at the judgement of the investigator, but will require regular brain imaging of the disease site.
• Major surgical procedure or serious trauma within 30 days prior to the first dose of the drug or major surgical procedure planned within 30 days of the first dose of the drug.
• Live or live attenuated vaccine administered within 30 days prior to the first dose or planned to be administered during the study period; inactivated vaccines are permitted.
• Known hypersensitivity to any component of the study drug.

Sponsors & Collaborators

• Henan Cancer Hospital: lead

Study Sites (4)

The First Affiliated Hospital of Henan University of Science and Technolog

Luoyang, Henan, China

Location

Xinxiang Central Hospital

Xinxiang, Henan, 450052, China

Location

Henan cancer hospital,

Zhengzhou, Henan, 450052, China

Location

Zhengzhou Third People's Hospital"

Zhengzhou, Henan, 450052, China

Location

MeSH Terms

Interventions

tislelizumab

Study Officials

• Qiming Wang

  Henan Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qiming Wang

CONTACT

+86-0371-65588421; qimingwang1006@126.com

Shuxiang Ma

CONTACT

+86-0371-65588421; zlyymashuxiang4175@zzu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: January 7, 2025
• First Posted: January 27, 2025
• Study Start: January 15, 2025
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): December 15, 2027
• Last Updated: January 27, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)