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

NCT05574998 | Unknown Phase 2

• 2 other identifiers: YXLL-KY-2020(073)ChiCTR2100042088
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Non-Small-Cell Lung Cancer

Keywords

Non-Small-Cell Lung Cancer; Recombinant human endostatin

Outcome Measures

Primary Outcomes (1)

• PFS

  Progression-free survival

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months

Secondary Outcomes (2)

• OS

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months

• ORR

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months

Study Arms (1)

Recombinant Human Endostatin(Endostar) in Combination With Platinum-Based Doublet Chemotherapy

EXPERIMENTAL

The specific treatment regimen is as follows: Non-squamous NSCLC: Endostar (210 mg, 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, 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.

Drug: Recombinant human endostatin (Endostar)

Interventions

Recombinant human endostatin (Endostar) DRUG

The specific treatment regimen is as follows: Non-squamous NSCLC: Endostar (210 mg, 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, 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.

Also known as: Carboplatin, Cisplatin, Pemetrexed, Paclitaxel

Recombinant Human Endostatin(Endostar) in Combination With Platinum-Based Doublet Chemotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• The molecular testing for EGFR mutation,ALK and ROS1 is all negative.
• 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.
• At least one measurable lesion as determined by RECIST criteria.
• Male or female patients, age: 18-75 years of age.
• Performance score 0-1 based on Eastern Cooperative Oncology Group (ECOG) test.
• Expected survival period \>= 12 weeks.
• Serum absolute number of neutrophils \>= 1.5 x 10\^9/L, platelet \>= 100 x 10\^9/L,and hemoglobin \>= 90g/L.
• Serum bilirubin \<= 1.5 times ULNL, aspartate aminotransferase (AST) and adenosine triphosphate(ALT) \<= 2.5 times ULN, alkaline phosphatase \<= 5 times ULN.
• Serum creatinine \<= the ULN or creatinine clearance \>= 60 mL/min.
• Patients who had previously undergone surgery have recovered for more than 4 weeks from the beginning of the project.
• 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).

You may not qualify if:

• 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.
• Existing severe acute infections that are not under control; Or suppurative and chronic infections with delayed healing.
• 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.
• 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.
• People with tendency of bleeding. 8.Other conditions that the investigator considers to be inappropriate for the patient to participate in this trial.

Sponsors & Collaborators

• Qianfoshan Hospital: lead

Study Sites (1)

The First Affiliated Hospital of Shandong First Medical University

Jinan, Shandong, 250014, China

RECRUITING

Related Publications (6)

• Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947-57. doi: 10.1056/NEJMoa0810699. Epub 2009 Aug 19.

  PMID: 19692680 RESULT

• Rinaldi M, Cauchi C, Gridelli C. First line chemotherapy in advanced or metastatic NSCLC. Ann Oncol. 2006 May;17 Suppl 5:v64-7. doi: 10.1093/annonc/mdj953.

  PMID: 16807466 RESULT

• Wang J, Sun Y, Liu Y, Yu Q, Zhang Y, Li K, Zhu Y, Zhou Q, Hou M, Guan Z, Li W, Zhuang W, Wang D, Liang H, Qin F, Lu H, Liu X, Sun H, Zhang Y, Wang J, Luo S, Yang R, Tu Y, Wang X, Song S, Zhou J, You L, Wang J, Yao C. [Results of randomized, multicenter, double-blind phase III trial of rh-endostatin (YH-16) in treatment of advanced non-small cell lung cancer patients]. Zhongguo Fei Ai Za Zhi. 2005 Aug 20;8(4):283-90. doi: 10.3779/j.issn.1009-3419.2005.04.07. Chinese.

  PMID: 21108883 RESULT

• Zhai Y, Ma H, Hui Z, Zhao L, Li D, Liang J, Wang X, Xu L, Chen B, Tang Y, Wu R, Xu Y, Pang Q, Chen M, Wang L. HELPER study: A phase II trial of continuous infusion of endostar combined with concurrent etoposide plus cisplatin and radiotherapy for treatment of unresectable stage III non-small-cell lung cancer. Radiother Oncol. 2019 Feb;131:27-34. doi: 10.1016/j.radonc.2018.10.032. Epub 2018 Dec 17.

  PMID: 30773184 RESULT

• Hansma AH, Broxterman HJ, van der Horst I, Yuana Y, Boven E, Giaccone G, Pinedo HM, Hoekman K. Recombinant human endostatin administered as a 28-day continuous intravenous infusion, followed by daily subcutaneous injections: a phase I and pharmacokinetic study in patients with advanced cancer. Ann Oncol. 2005 Oct;16(10):1695-701. doi: 10.1093/annonc/mdi318. Epub 2005 Jul 12.

  PMID: 16012180 RESULT

• Liu X, Guo Z, Su L, Zuo A, Gao M, Ji X, Lu J, Yang S, Jiang Y, Lu D. The efficacy and safety of continuous intravenous infusion of rh-endostatin combined with platinum-based doublet chemotherapy for advanced non-small-cell lung cancer. Invest New Drugs. 2024 Jun;42(3):309-317. doi: 10.1007/s10637-024-01439-x. Epub 2024 May 3.

  PMID: 38700579 DERIVED

Related Links

• N Engl J Med. 2009 Sep 3;361(10):947-57. doi: 10.1056/NEJMoa0810699. Epub 2009 Aug 19.
• Ann Oncol. 2006 May;17 Suppl 5:v64-7. Review.
• Zhongguo Fei Ai Za Zhi. 2005 Aug 20;8(4):283-90.
• Radiother Oncol. 2019 Feb;131:27-34
• Ann Oncol. 2005 Oct;16(10):1695-701. Epub 2005 Jul 12.

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Endostatins; endostar protein; Carboplatin; Cisplatin; Pemetrexed; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Angiostatic Proteins; Angiogenic Proteins; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Collagen Type XVIII; Non-Fibrillar Collagens; Collagen; Extracellular Matrix Proteins; Scleroproteins; Biological Factors; Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Degan Lu, professor

  Shandong First Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Degan Lu, professor

CONTACT

18753157623; deganlu@126.com

Study Design

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

Study Record Dates

• First Submitted: October 6, 2022
• First Posted: October 12, 2022
• Study Start: February 1, 2021
• Primary Completion: February 1, 2024
• Study Completion: April 1, 2024
• Last Updated: October 12, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)