Status:
ACTIVE_NOT_RECRUITING
Phase II Study of Chemotherapy and PD-1 Inhibitor Combination With Autologous CIK Cell Immunotherapy to Treat Lung Cancer
Lead Sponsor:
Tianjin Medical University Cancer Institute and Hospital
Conditions:
Non-small Cell Lung Cancer Metastatic
First-line Treatment
Eligibility:
All Genders
18-75 years
Phase:
PHASE2
Brief Summary
This prospective, multi-center, open-label, phase II, randomized controlled trial (CCICC-002b) is to evaluate the efficacy and safety of autologous cytokine-induced killer cell immunotherapy in combin...
Eligibility Criteria
Inclusion
- Signed written informed consent prior to any trial-related procedures.
- Age ≥18 and ≤75 years.
- Histologically or cytologically confirmed stage IV NSCLC (IASLC/UICC 8th edition TNM staging) with no prior systemic therapy for advanced disease.
- For enrolled adenocarcinoma patients: Absence of EGFR-sensitive mutations and ALK gene fusion alterations confirmed by histological specimens.
- At least one radiologically measurable lesion per RECIST v1.1. Lesions within prior radiotherapy fields may be considered measurable if progression is confirmed.
- No prior systemic antitumor therapy for advanced/metastatic disease. Subjects who received:
- Platinum-based adjuvant/neoadjuvant chemotherapy, or
- Definitive chemoradiotherapy for limited-stage disease are eligible if disease progression/recurrence occurred ≥6 months after last chemotherapy.
- Asymptomatic or stable brain metastases after local treatment are permitted if all criteria are met:
- Measurable extracranial lesions
- No CNS symptoms or symptom stability for ≥2 weeks
- No corticosteroids required, OR discontinued corticosteroids ≥7 days before first dose, OR stable corticosteroid dose ≤10 mg/day prednisone equivalent for ≥7 days.
- Palliative radiotherapy (including brain RT for symptomatic metastases) is allowed if completed ≥1 week before first dose and radiation-related toxicities have recovered to ≤Grade 1 (CTCAE v5.0, excluding alopecia).
- ECOG performance status 0-1.
- Life expectancy \>3 months.
- Adequate organ function meeting all laboratory criteria:
- Absolute neutrophil count (ANC) ≥1.5×10⁹/L without granulocyte colony-stimulating factor support within 14 days.
- Platelets ≥100×10⁹/L without transfusion within 14 days.
- Hemoglobin \>9 g/dL without transfusion or erythropoietin within 14 days.
- Total bilirubin ≤1.5×ULN.
- AST/ALT ≤2.5×ULN (≤5×ULN if liver metastases present).
- Serum creatinine ≤1.5×ULN AND creatinine clearance (Cockcroft-Gault formula) ≥60 mL/min.
- INR/PT ≤1.5×ULN.
- Normal thyroid function (TSH within normal range). Subjects with baseline TSH outside normal range may enroll if FT3/FT4 are normal.
- Normal myocardial enzyme profile.
- For women of childbearing potential: Negative urine/serum pregnancy test within 3 days prior to first dose (Cycle 1 Day 1). Non-childbearing potential is defined as ≥1 year post-menopause, surgically sterilized, or hysterectomy.
- All subjects (regardless of gender) at risk of conception must use highly effective contraception (failure rate \<1% annually) during treatment and for 120 days (or 180 days per protocol) after last dose.
Exclusion
- Pathologically confirmed small cell lung cancer (SCLC), including mixed SCLC-NSCLC histology.
- Prior radiotherapy meeting any of the following:
- Radiation to ≥30% of bone marrow within 14 days before first dose
- Lung radiation \>30 Gy within 6 weeks before treatment (subjects must have recovered to ≤Grade 1 toxicity, no corticosteroid requirement, and no history of radiation pneumonitis)
- Palliative radiotherapy completed ≤7 days before first dose
- Diagnosis of malignancies other than NSCLC within 5 years before first dose (except cured basal cell carcinoma, squamous cell carcinoma, or resected carcinoma in situ).
- Current participation in interventional clinical trials or receipt of investigational drugs/devices within 4 weeks before first dose.
- Prior therapy with anti-PD-1/PD-L1/PD-L2 agents or drugs targeting other T-cell co-stimulatory/checkpoint pathways (e.g., CTLA-4, OX-40, CD137).
- Systemic treatment with Chinese herbal medicines (for lung cancer indications) or immunomodulatory agents (e.g., thymosin, interferon, interleukin) within 14 days before first dose (except local pleural control).
- Active autoimmune disease requiring systemic treatment (e.g., disease-modifying agents, corticosteroids, immunosuppressants) within 2 years before first dose. Replacement therapies (e.g., thyroid hormone, insulin, physiologic corticosteroids) are permitted.
- Systemic corticosteroids (\>10 mg/day prednisone equivalent) or immunosuppressive therapy within 7 days before first dose (excluding topical/nasal/inhaled corticosteroids).
- \*Note: Physiologic corticosteroid doses (≤10 mg/day prednisone equivalent) are allowed.\*
- Clinically uncontrolled pleural/peritoneal effusion (subjects with stable effusion not requiring drainage or ≥3 days post-drainage may enroll).
- History of allogeneic organ transplantation (except corneal transplants) or hematopoietic stem cell transplantation.
- Known hypersensitivity to sintilimab, pemetrexed, nab-paclitaxel, carboplatin, or their excipients.
- Failure to recover from prior intervention-related toxicities (≤Grade 1 or baseline, excluding alopecia/fatigue) before treatment initiation.
- Known HIV infection (HIV 1/2 antibody positive).
- Untreated active hepatitis B (HBsAg-positive with HBV-DNA \> upper limit of normal \[ULN\] at local laboratory).
- \*Exceptions:\*
- HBV-DNA \<1000 copies/ml (200 IU/ml) before first dose with ongoing antiviral prophylaxis during chemotherapy
- Anti-HBc(+) subjects with HBsAg(-), anti-HBs(-), and undetectable HBV-DNA may enroll without prophylaxis but require close monitoring
- Active HCV infection (HCV antibody-positive with detectable HCV-RNA).
- Live vaccination within 30 days before Cycle 1 Day 1. \*Note: Inactivated vaccines (e.g., seasonal influenza) are permitted; live attenuated vaccines (e.g., nasal flu vaccine) are prohibited.\*
- Pregnancy or lactation.
- Severe uncontrolled systemic diseases including:
- Symptomatic ECG abnormalities (e.g., complete left bundle branch block, ≥Grade 2 AV block, ventricular arrhythmias, atrial fibrillation)
- Unstable angina, congestive heart failure (NYHA class ≥2)
- Myocardial infarction within 6 months
- Poorly controlled hypertension (SBP \>140 mmHg/DBP \>90 mmHg)
- Non-infectious pneumonitis requiring steroids within 1 year or active interstitial lung disease
- Active tuberculosis
- Uncontrolled active infection requiring systemic therapy
- Clinically active diverticulitis, abdominal abscess, gastrointestinal obstruction
- Decompensated liver disease (e.g., cirrhosis, active hepatitis)
- Poorly controlled diabetes (fasting glucose \>10 mmol/L)
- Urine protein ≥++ with 24-hour protein \>1.0 g
- Uncontrolled hypercalcemia (\>1.5 mmol/L ionized calcium or corrected serum calcium \>ULN)
- Non-healing wounds/fractures
- Psychiatric disorders impairing protocol compliance
- Any condition that may interfere with study results, compromise subject safety, or preclude full participation as judged by the investigator.
Key Trial Info
Start Date :
March 31 2021
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 31 2026
Estimated Enrollment :
156 Patients enrolled
Trial Details
Trial ID
NCT04836728
Start Date
March 31 2021
End Date
December 31 2026
Last Update
March 13 2025
Active Locations (1)
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1
Tianjin Medical University Cancer Institute and Hospital
Tianjin, Tianjin Municipality, China, 300060