Trial Title:
Auto-HSCT-Supported Dose-Dense Chemotherapy with Adebrelimab As First-Line Treatment for ES-SCLC
NCT ID:
NCT06597513
Condition:
Extensive Stage Small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Conditions: Keywords:
Auto-HSCT
Adebrelimab
Dose-Dense Chemotherapy
Etoposide
Carboplatin
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
auto-HSCT-Supported Dose-Dense Chemotherapy With Adebrelimab
Description:
Induction:
Two 21-day cycles of standard-dose etoposide 80-100 mg/m² on days 1-3 and carboplatin AUC
5-6 on day 1.
Those without disease progression will advance to consolidation treatment.
Consolidation:
Stem cell mobilization with G-CSF will be start when white blood cell count is at its
nadir post-chemotherapy.
After recovery, peripheral blood stem cells will be collected via apheresis, evaluated,
and cryopreserved if adequate.
Dose-dense etoposide 160-200 mg/m² on days 1-3 and carboplatin AUC 10-12 on day 1 for two
21-day cycles.
Within 48-72 hours after the first cycle, autologous peripheral blood stem cells will be
reinfused with G-CSF.
Further consolidation will depend on hematopoietic recovery with standard-dose EC plus
adebrelimab 1200 mg on day 1 for four 21-day cycles.
Maintenance:
Adebrelimab 1200 mg every 21 days will be given until disease progression, intolerable
toxicity, death, patient withdrawal, or investigator decision.
Arm group label:
auto-HSCT-Supported Dose-Dense Chemotherapy With Adebrelimab
Other name:
auto-HSCT, Dose-Dense Chemotherapy, Adebrelimab
Summary:
The goal of this clinical trial is to learn if hematopoietic stem cell
transplantation-supported dose-dense chemotherepy with adebrelimb works to treat
extensive-stage small-cell lung cancer in adults. It will also assess the safety of this
treatment approach.
The main questions it aims to answer are:
Does hematopoietic stem cell transplantation-supported dose-dense chemotherepy with
adebrelimb improve the median progression free survival and 12-months overall survival
rates? What medical problems do participants experience whild undergoing this treatment?
Participants will:
Complete two 21-days cycles of standard-dose etoposide and carboplatin, followed by G-CSF
for stem cell mobilization.
Receive dose-dense chemotherapy followed by autologous stem cell reinfusion for two
21-day cycles.
If eligible, participants will receive etoposide and carboplatin plus adebrelimab for
four cycles.
Finally, participants may enter a maintenance phase with adebrelimab.
Throughout the trial, participants will:
Visit the clinic every 21 days for check-ups and tests. Imaging examination every 6
weeks. Followed up by telephone every 2 months
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Pathologically confirmed small cell lung cancer (SCLC) staged as extensive-stage
(ES-SCLC) according to the Veterans Administration Lung Study Group (VALG)
classification.
2. ES-SCLC dose not received prior systemic treatment.
3. History of localized-stage SCLC with prior radiotherapy and chemotherapy, with the
requirement for definitive treatment, and a minimum of 6 months interval from the
last treatment to diagnosis of ES-SCLC.
4. CT or MRI scan ≤28 days prior to the first dose of study medication, with at least
one target lesion that has not been irradiated (RECIST v1.1 criteria).
5. Male or female patients aged ≥18 and ≤70 years.
6. ECOG Performance Status of 0 or 1.
7. Life expectancy ≥12 weeks.
8. Adequate organ system function (excluding use of any blood components or growth
factors during screening).
9. Male or female participants must agree to use appropriate contraception (e.g.,
intrauterine device, contraceptive pills, or condoms) from the start of the study
treatment until 6 months after the last study treatment; women of childbearing
potential must have a negative pregnancy test within 7 days prior to enrollment.
10. Subjects voluntarily participate in this study and sign the informed consent form
(ICF).
Exclusion Criteria:
1. Histologically or cytologically confirmed mixed SCLC and NSCLC.
2. Prior treatment with any T-cell co-stimulatory or immune checkpoint inhibitors,
including but not limited to cytotoxic T lymphocyte-associated antigen-4 (CTLA-4)
inhibitors, PD-1 inhibitors, PD-L1/2 inhibitors, or other T-cell targeted agents.
3. Prior treatment with vascular endothelial growth factor (VEGF) or vascular
endothelial growth factor receptor (VEGFR) inhibitors.
4. Symptomatic brain metastases, leptomeningeal disease, or spinal cord compression.
For treated brain metastases, the following criteria must be met: no progression on
MRI ≥4 weeks post-treatment, completion of treatment ≥28 days before the first dose
of study drug, and no need for systemic corticosteroids (>10 mg/day prednisone or
equivalent) ≤14 days before the first dose.
5. Hematologic disorders including, but not limited to, lymphoma, acute or chronic
leukemia, multiple myeloma, aplastic anemia, or myelodysplastic syndromes.
6. Symptomatic third-space fluid accumulation, such as uncontrolled pericardial
effusion, pleural effusion, or ascites despite drainage or other treatments.
7. Active, known, or suspected autoimmune diseases. Exceptions include vitiligo, type 1
diabetes, autoimmune thyroiditis with only hormone replacement therapy, or
conditions unlikely to relapse without external stimuli.
8. Use of systemic corticosteroids (>10 mg/day prednisone or equivalent) or other
immunosuppressants ≤14 days before the first dose of study drug. Inhaled or topical
corticosteroids and adrenal replacement therapy are allowed if no active autoimmune
disease.
9. Receipt of or planned vaccination with live vaccines ≤4 weeks before the first dose
of study drug.
10. Interstitial lung disease, drug-induced pneumonitis, radiation pneumonitis requiring
corticosteroids, active pneumonia, or severe pulmonary dysfunction.
11. Active tuberculosis or history of active tuberculosis ≤48 weeks before screening,
regardless of treatment status.
12. Toxicities from prior anticancer treatment other than alopecia and fatigue must have
resolved to CTCAE v4.03 ≤ Grade 1 before the first dose. Long-term sequelae such as
platinum-based neurotoxicity are allowed if anticipated to be stable.
13. Imaging (CT or MRI) showing tumor invasion of major vessels, hemoptysis symptoms
within 3 months before screening, or daily hemoptysis ≥2.5 mL.
14. Minor surgery (including catheter placement) ≤48 hours before the first dose of
study drug.
15. Current or recent use of aspirin (>325 mg/day) or other nonsteroidal
anti-inflammatory drugs known to inhibit platelet function ≤10 days before the first
dose.
16. Current or recent use of full-dose oral or parenteral anticoagulants or
thrombolytics ≤10 days before the first dose. Preventive anticoagulation is allowed.
17. Known hereditary bleeding disorders or coagulation dysfunction. Significant bleeding
symptoms or clear bleeding tendencies (e.g., gastrointestinal bleeding, bleeding
ulcers, baseline stool occult blood ++ or more) within 12 weeks before screening.
18. History of thromboembolic events within 24 weeks before signing the ICF, including
stroke (including transient ischemic attack, hemorrhagic stroke, or infarction),
deep vein thrombosis, or pulmonary embolism.
19. Uncontrolled hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood
pressure ≥90 mmHg), hypertensive crises, or history of hypertensive encephalopathy.
20. History of gastrointestinal ulcers, perforation, corrosive esophagitis or gastritis,
inflammatory bowel disease, diverticulitis, abdominal fistula, tracheoesophageal
fistula, or intra-abdominal abscess within 24 weeks before signing the ICF.
21. Uncontrolled cardiac symptoms or diseases, including: (1) NYHA Class ≥II heart
failure; (2) unstable angina; (3) myocardial infarction within 24 weeks; (4)
clinically significant supraventricular or ventricular arrhythmias requiring
treatment or intervention.
22. Known allergy to study drug or excipients, or a history of severe allergic reactions
to any monoclonal antibody.
23. Other malignancies within 5 years before the first dose, except for adequately
treated cervical carcinoma in situ, basal cell carcinoma, squamous cell carcinoma of
the skin, locally excised prostate cancer, or ductal carcinoma in situ with minimal
risk of metastasis and expected cure.
24. Known psychiatric disorders, alcohol abuse, drug abuse, or substance misuse.
25. Positive HBsAg with HBV DNA levels exceeding normal limits (1000 copies/ml or 500
IU/ml), or positive HCV (HCV RNA or HCV Ab indicating acute or chronic infection);
known HIV positive or acquired immunodeficiency syndrome (AIDS).
26. Uncontrolled or symptomatic hypercalcemia.
27. Receipt of any investigational drug or participation in another interventional
clinical trial ≤4 weeks before signing the ICF.
28. History of allogeneic bone marrow transplantation or solid organ transplantation.
29. Use of systemic immunosuppressive drugs ≤2 weeks before randomization.
30. History of hypersensitivity reactions to chimeric or humanized antibodies or fusion
proteins, carboplatin, or etoposide.
31. Any other factors that, in the investigator's judgment, may lead to premature
discontinuation of the study, including non-compliance, severe concurrent illness
(including psychiatric illness), significant laboratory abnormalities, or factors
affecting the safety or data collection.
Gender:
All
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Start date:
December 2024
Completion date:
December 2026
Lead sponsor:
Agency:
Zhou Chengzhi
Agency class:
Other
Source:
Guangzhou Institute of Respiratory Disease
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06597513
