Apatinib Combine With Platinum-Based Doublet Chemotherapy for First-line Treatment of Advanced NSCLC

NCT03201146 | Unknown Phase 1

• 1 other identifier: 2009L03464
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and clinical activity of Apatinib in combination with AP(Pemetrexed/Carboplatin) or AC(Pemetrexed/Carboplatin) as first-line chemotherapy in subjects with advanced EGFR wild type non-squamous non-small cell lung cancer(NSCLC).

Conditions

Lung Cancer; Non Small Cell Lung Cancer; Combination Chemotherapy; Apatinib

Outcome Measures

Primary Outcomes (1)

• Objective response rate(ORR)

  To determine ORR of Apatinib in combination with AP or AC in subjects with advanced EGFR wild type non-squamous non-small cell lung cancer. ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1

  Up to 36 months

Secondary Outcomes (4)

• Progression-free survival (PFS)

  Up to 36 months

• Disease Control Rate (DCR)

  Up to 36 months

• median Overall Survival

  Up to 36 months

• One-year Overall Survival Rate

  Up to 36 months

Study Arms (5)

Apatinib 750mg + AP or AC

EXPERIMENTAL

Phase 1 study of Apatinib in combination with platinum-based doublet chemotherapy.

Drug: AP or AC; Drug: Apatinib 750mg

Apatinib 500mg + AP or AC

EXPERIMENTAL

Phase 1 study of Apatinib in combination with platinum-based doublet chemotherapy.

Drug: AP or AC; Drug: Apatinib 500mg

Apatinib 250mg + AP or AC

EXPERIMENTAL

Phase 1 study of Apatinib in combination with platinum-based doublet chemotherapy(PBDC).

Drug: AP or AC; Drug: Apatinib 250mg

Apatinib

EXPERIMENTAL

Phase 2 study of Apatinib in combination with platinum-based doublet chemotherapy(PBDC).

Drug: Apatinib; Drug: AP or AC

AP or AC

ACTIVE COMPARATOR

Pemetrexed/Cisplatin(AP) or Pemetrexed/Carboplatin(AC), The platinum-based doublet chemotherapy, as the control group in the phase 2 study.

Drug: AP or AC

Interventions

Apatinib DRUG

Doses to be determined following the completion of Phase I of the study.

Also known as: YN968D1

Apatinib

AP or AC DRUG

Pemetrexed(A) 500mg/m2, IV, Day 1; Cisplatin(P) 25mg/m2,IV,Day 1-3 or Carboplatin(C) area under curve(AUC)=5, IV, Day 1; AP or AC will be administered every 21 days starting on Day 1.

Also known as: Pemetrexed/Cisplatin or Pemetrexed/Carboplatin

AP or AC; Apatinib; Apatinib 250mg + AP or AC; Apatinib 500mg + AP or AC; Apatinib 750mg + AP or AC

Apatinib 250mg DRUG

250mg/d,q.d.,p.o.every 21 days.

Also known as: YN968D1

Apatinib 250mg + AP or AC

Apatinib 500mg DRUG

500mg/d,q.d.,p.o.every 21 days.

Also known as: YN968D1

Apatinib 500mg + AP or AC

Apatinib 750mg DRUG

750mg/d,q.d.,p.o.every 21 days.

Also known as: YN968D1

Apatinib 750mg + AP or AC

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Signed the informed consent form prior to patient entry.
• \. ≥ 18 and ≤ 70 years of age.
• \. Histologically or pathologically confirmed non-squamous EGFR wild-type, ALK-rearrangement negative, stage IV non-small cell lung cancer(NSCLC).
• \. Must have at least one measurable lesion as per RECIST 1.1 defined as a lesion that is 10mm in longest diameter or lymph node that is 15mm in short axis imaged by CT scan, prior topical treatment, such as radiotherapy or cryosurgery to the lesions is not allowed.
• \. No prior systemic chemotherapy for advanced or metastatic NSCLC.
• \. Eastern Cooperative Oncology Group(ECOG) performance status 0 or 1.
• \. Life expectancy of more than 3 months.
• \. Adequate bone marrow function : WBC ≥ 3.0 ×10 E+9/L, neutrophil ≥ 1.5 × 10 E+9/L, platelets ≥ 80 × 10E+9/L,Hb ≥ 10.0g/dL.
• \. Adequate hepatic and renal functions: a total bilirubin (TBil) of ≤1.5 upper normal limitation (UNL), a alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) of ≤2.5 UNL or ≤5 UNL in case of liver metastasis, a creatinine (Cr) of ≤ 1.5 UNL; a creatinine clearance rate ≥ 50ml/min (Cockcroft-Gault).
• \. With normal coagulation function: INR and PTT, each ≤ 1.5 x ULN.
• \. Adequate cardiovascular function: left ventricular ejection fraction (LVEF) ≥ 50%, QTcF ≤ 450 msec.
• \. Alkaline phosphatase ≤ 2.5 x ULN.
• \. The subjects are willing to coordinate with the follow-up with good compliance.
• \. Female subjects of child-bearing potential must agree to use contraceptive measures starting 1 week before the administration of the first dose of apatinib until 8 weeks after discontinuing study drug. Male subjects must agree to use contraceptive measures during the study and 8 weeks after last dose of study drug.

You may not qualify if:

• \. Patients with active brain metastasis, carcinomatous meningitis, or spinal compression, or disease of brain or pia mater according to the screening test, imaging, CT or MRI tests (patients who have completed the treatment and in a stable condition 21 days before screening could be included, but brain MRI, CT or venography is required to confirm that there are no brain hemorrhage symptoms).
• \. Patients with uncontrollable hypertension (systolic blood pressure\> 140 mmHg, diastolic blood pressure\> 90 mmHg, despite optimal drug therapy).
• \. Patients with with grade Ⅱ myocardial ischemia or myocardial infarction, poor control of arrhythmias (including QTc interval male ≥ 450 ms, female ≥470 ms).
• \. According to NYHA standard, grade Ⅲ \~ Ⅳ heart failure, or cardiac color Doppler ultrasound examination showed left ventricular ejection fraction (LVEF) \<50%.
• \. Coagulation dysfunction (INR\> 1.5, PT\> ULN +4s or APTT\> 1.5 ULN), with bleeding tendency or ongoing thrombolysis or anti-blood coagulation treatment.
• \. Patients treated with anticoagulation agents or Vitamin K antagonist such as Warfarin, heparin, or other similar drugs.
• \. Patients who had obvious hemoptysis within 2 months before screening, or experienced daily hemoptysis with a volume more than half a tea spoon (2.5ml) or above.
• \. Patients who experienced bleeding symptoms of clinical significance within 3 months before screening, or with confirmed bleeding tendency such as hemorrhage of digestive tract, hemorrhagic gastric ulcer, baseline occult blood in stool ++ and above, or vasculitis, etc.
• \. Patients who manifested arterial/venous thrombus events, e.g. cerebrovascular accident (including transient ischemic attack), deep venous thrombosis and pulmonary embolism, etc., within 12 months before screening.
• \. Known genetic or acquired bleeding or bleeding tendency (such as hemophilia, blood coagulation dysfunction, thrombocytopenia, and hypersplenism, etc.).
• \. Patients who have unhealed wounds or fractures for a long time.
• \. Patients who received major surgical operations or experienced severe traumatic injuries, bone fracture, or ulcers within 4 weeks before screening.
• \. Patients with obvious factors affecting absorption of oral drugs, such as difficulties in swallowing, chronic diarrhea and intestinal obstruction, etc.
• \. Occurrence of abdominal fistula, gastrointestinal perforation, or intraperitoneal abscess within 6 months before screening.
• \. Patients whose routine urine tests indicate that urine protein ≥ ++ or verifies that the 24-h urine protein quantitation ≥ 1.0 g.

Sponsors & Collaborators

• West China Hospital: lead
• Jiangsu HengRui Medicine Co., Ltd.: collaborator

Study Sites (1)

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

Related Publications (1)

• Li J, Zhao X, Chen L, Guo H, Lv F, Jia K, Yv K, Wang F, Li C, Qian J, Zheng C, Zuo Y. Safety and pharmacokinetics of novel selective vascular endothelial growth factor receptor-2 inhibitor YN968D1 in patients with advanced malignancies. BMC Cancer. 2010 Oct 5;10:529. doi: 10.1186/1471-2407-10-529.

  PMID: 20923544 RESULT

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

apatinib; Pemetrexed; Cisplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Central Study Contacts

You Lu, MD

CONTACT

86-028-85422114; radyoulu@hotmail.com

Meijuan Huang, MD

CONTACT

86-028-85422114; hmj107@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: June 25, 2017
• First Posted: June 28, 2017
• Study Start: June 27, 2017
• Primary Completion: July 1, 2020
• Study Completion: August 1, 2020
• Last Updated: November 17, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)