First-Line Treatment of Advanced Non-Small-Cell Lung Cancer With Negative Driver Gene: a Multicenter, Single-Arm Trial

• Status: Recruiting
• Trial end date: 2024-04-01
• Target enrollment: 0
• Participant gender: All

Summary

To evaluate the efficacy and safety of recombinant human endostatin (Endostar) combined with platinum-based doublet chemotherapy as the first-line therapy for patients with driver-gene-negative advanced non-small cell lung cancer(NSCLC).

This study is an exploratory single-arm study. The specific treatment regimen is as follows:

Non-squamous NSCLC: Endostar (210 mg, continuous intravenous infusion (CIV) for 120 h) is started on the first day of each treatment cycle and administered every three weeks. Carboplatin AUC 5-6 mg/ml/min or cisplatin 75 mg/m2 (d4) +pemetrexed 500 mg/m2 (d4) Q3W is administered in this regimen for 4 cycles followed by Endostar plus pemetrexed until disease progression or intolerable toxicity.

Squamous NSCLC: Endostar (210 mg, continuous intravenous infusion (CIV) for 120 hours) is started on the first day of each treatment cycle and administered every three weeks. Carboplatin AUC 5-6 mg/ml/min or cisplatin 75 mg/m2 (d4) + paclitaxel 175 mg/m2 (d4) Q3W.Endostar is administered after 4 cycles of this treatment regimen until disease progression or intolerable toxicity developed.

Patients are assessed for measurable disease at baseline, 6 weeks, 12 weeks after starting treatment, and every 9 weeks thereafter according to RECIST 1.1 criteria during the treatment period until disease progression or intolerable toxicity withdrawal. Following discontinuation of treatment, subjects are followed for survival status every 3 months until death. Subject safety was assessed during treatment according to NCI CTCAE Version 4.0 criteria. Subjects who experience an AE should be followed until the AE returns to baseline. The primary endpoints is Progression-free survival (PFS) . Secondary endpoints include objective response rate (ORR), overall survival (OS) and safety (NCI CTCAE v 4.0).

Statistical methods: The PFS curve was estimated using the Kaplan-Meier method for the largest population to be analyzed. The confidence interval method was used as the criterion for the main analysis. OS was calculated in the same way as the secondary endpoint. Descriptive statistics will be used to analyze ORR, DCR, etc.

It is expected that continuous intravenous Endostar combined with platinum-based doublet chemotherapy as first-line treatment will prolong median PFS and OS in patients with driver gene-negative advanced NSCLC.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Qianfoshan Hospital
• Treatments: Carboplatin; Cisplatin; Endostar protein; Endostatins; Paclitaxel; Pemetrexed

Criteria

Inclusion Criteria:

1. Metastatic NSCLC is histologically or cytologically proven to be inoperable and cannot receive radical concurrent chemoradiotherapy. The conventional TNM stage was identified as stage IIIa-Ⅳb according to the International Association for the Study of Lung Cancer and the American Joint Committee on the Classification of Cancer 8th edition TNM Staging of Lung Cance.

2. The molecular testing for EGFR mutation,ALK and ROS1 is all negative.

3. Patients who had not previously received systemic radiotherapy and chemotherapy or who had relapsed for more than 6 months of follow-up after onset of adjuvant chemotherapy.

4. At least one measurable lesion as determined by RECIST criteria.

5. Male or female patients, age: 18-75 years of age.

6. Performance score 0-1 based on Eastern Cooperative Oncology Group (ECOG) test.

7. Expected survival period >= 12 weeks.

8. Serum absolute number of neutrophils >= 1.5 x 10^9/L, platelet >= 100 x 10^9/L,and hemoglobin >= 90g/L.

9. Serum bilirubin <= 1.5 times ULNL, aspartate aminotransferase (AST) and adenosine triphosphate(ALT) <= 2.5 times ULN, alkaline phosphatase <= 5 times ULN.

10. Serum creatinine <= the ULN or creatinine clearance >= 60 mL/min.

11. Patients who had previously undergone surgery have recovered for more than 4 weeks from the beginning of the project.

12. Women with an intact uterus must have a negative pregnancy test within 28 days prior to enrolement in the study (unless it was 24 months after amenorrhea). If the pregnancy test is more than 7 days prior to initial dosing, a urine pregnancy test is required for verification (within 7 days prior to initial dosing).

13. Sign the inform consent form with good compliance. Exclusion criteria：

1.Intolerance to platinum therapy or allergy to platinum drugs. 2.Allergic to recombinant human endostatin (endostar) and its any components. 3.Pregnancy or breastfeeding women or women who may be pregnant but are unwilling to take appropriate contraception.

4.Existing severe acute infections that are not under control; Or suppurative and chronic infections with delayed healing.

5.Pre-existing serious heart disease, including: congestive heart failure, uncontrolled high-risk arrhythmias, unstable angina pectoris, myocardial infarction, severe valvular heart disease, and refractory hypertension.

6.People suffering from uncontrollable neuropsychiatric diseases or mental disorders had poor compliance and were unable to cooperate and describe treatment responses; The conditions of patients with primary brain tumor or central nerve metastatic tumor were uncontrollable and the symptoms of cranial hypertension or neuropsychiatric were obvious.

7.People with tendency of bleeding. 8.Other conditions that the investigator considers to be inappropriate for the patient to participate in this trial.