Efficacy and Safety of Anlotinib Plus Platinum Plus Pemetrexed in T790M-negative NSCLC

NCT03706287 | Unknown Phase 1

• 1 other identifier: ALTER-L022
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 6

Brief Summary

This study is conducted to explore the safety and efficacy of anlotinib, a tyrosine kinase inhibitors of vascular endothelial growth factor receptor 2（VEGFR）、FGFR（fibroblast growth factor receptor）, platelet-derived growth factor receptor（PDGFR） and tumor cell proliferation related kinase c-Kit, combined with platinum plus pemetrexed in T790M mutation negative metastatic non-squamous non-small cell lung cancer(NSCLC) after the failure of EGFR-TKI.

Conditions

Lung Cancer Metastatic

Keywords

non small cell lung cancer; anlotinib; pemetrexed; T790M negative

Outcome Measures

Primary Outcomes (3)

• Progression-free survival (PFS)

  PFS defined as the time from first dose of study treatment until the first date of either objective disease progression or death due to any cause.

  Up to 24 months

• Dose limiting toxicity (DLT)

  Dose Limiting Toxicity (DLT) is referred to grade 3 non-hematological toxicity or grade 4 hematological toxicity according to NCI CTCAE 4.03 criteria

  Estimated about 6 months

• Maximum tolerance dose (MTD)

  Maximum Tolerance Dose (MTD) is the dose of treatment in the cohort where there are 2 cases of DLT reported.

  Estimated about 6 months

Secondary Outcomes (4)

• Objective response rate(ORR)

  Up to 24months

• Disease Control Rate (DCR)

  Up to 24months

• Duration of Response (DOR)

  Up to 24months

• Safety (Number of Participants with Adverse Events as a Measure of Safety and Tolerability)

  Until 21 day safety follow-up visit

Study Arms (1)

Anlotinib + AP/PC

EXPERIMENTAL

Drug: anlotinib 8mg + AP/PC; Drug: anlotinib 10mg + AP/PC; Drug: anlotinib 12mg + AP/PC; Drug: anlotinib + AP/PC

Interventions

anlotinib 8mg + AP/PC DRUG

anlotinib 8mg/d, q.d., p.o. 1-14days every 21 days 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

Anlotinib + AP/PC

anlotinib 10mg + AP/PC DRUG

anlotinib 10mg/d, q.d., p.o. 1-14days every 21 days 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

Anlotinib + AP/PC

anlotinib 12mg + AP/PC DRUG

anlotinib 12mg/d, q.d., p.o. 1-14days every 21 days 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

Anlotinib + AP/PC

anlotinib + AP/PC DRUG

anlotinib doses to be determined following the completion of Phase I of the study, q.d., p.o. 1-14days every 21 days 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.

Anlotinib + AP/PC

Eligibility Criteria

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

You may qualify if:

• ≥ 18 and ≤ 75 years of age. Signed the informed consent form prior to patient entry
• Histologically or pathologically confirmed non-squamous non-small cell lung cancer(NSCLC) with stage IV .
• Epidermal Growth Factor Receptor(EGFR)mutations confirmed by molecular detection (including, but not limited to 19 exon deletion and L858R) external pathological examination was accepted (including pathological or blood test results)
• Patients have only be treated with EGFR -TKIs（Tyrosine kinase inhibitors）including gefitinib, elotinib or icotinib, and received a best response of PR for ≥4months or SD for 6 months; disease has progressed recently according to RECIST 1.1 and negative for T790M detection（detection methods including ddPCR、ARMS or NGS） (For recurrent patients, adjuvant chemotherapy, neoadjuvant chemotherapy or neoadjuvant chemotherapy plus adjuvant were assessed for eligibility, and the last treatment time must be more than 6 months before enrollment）
• Must have at least one measurable lesion as per RECIST 1.1 defined as a lesion that is 10mm in longest diameter imaged by CT scan or MRI；prior topical treatment, such as radiotherapy cryosurgery to the lesions is not allowed in less than 3 months;
• Life expectancy ≥3 months.
• Eastern Cooperative Oncology Group(ECOG) performance status 0 or 1.
• Toxicity caused by prior anti-cancer treatments was restored to ≤ level 1 in CTC AE (4.0) , except alopecia;
• The blood routine examination need to be standard (no blood transfusion and blood products within 14 days, no g-csf and other hematopoietic stimulating factor correction) Hemoglobin（HB）≥90 g/L A Neutrophil count of （ANC）≥1.5×109/L A Platelet count of （PLT）≥80×109/L A Total bilirubin (TBil) of ≤1.5 upper normal limitation (UNL) A alanine aminotransferase (ALT) and a aspartate aminotransferase (AST) of ≤2.5 UNL, in case of liver metastasis ALAT and ASAT≤5 UNL A creatinine (Cr) of ≤1.5 UNL; a creatinine clearance rate ≥ 60ml/min (Cockcroft-Gault)
• The woman patients of childbearing age who must agree to take contraceptive methods during the research and within another 8 weeks after it and examined as negative in blood serum test or urine pregnancy test within 7 days before the research; the man patients who must agree to take contraceptive methods during the research and within another 8 weeks;
• Voluntarily joined the study and signed informed consent, with good compliance and follow-up.

You may not qualify if:

• Small Cell Lung Cancer mixed or squamous mixed;
• No squamous NSCLC with hemoptysis (\>50ml/day);
• Symptomatic brain metastases after treatment;
• Tumor locate within a distance of less than 5 mm from the large vessels, less than 2 cm from the bronchial tree, or has invaded local large vessels; tumor with cavum or necrotic obviously;
• Uncontrolled hypertension (systolic ≥150mmHg and/or diastolic ≥100mmHg, 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;note: Note: under the premise of International Normalized ratio (INR) of prothrombin time (PT) Less than or equal to 1.5, allow to administrate low-dose heparin (adult daily dose is 06000 \~ 12000 U) or low-dose aspirin (100 mg daily dosage or less) , for prophylactic purposes
• Patients whose routine urine tests indicate that urine protein ≥ ++ or verifies that the 24-h urine protein quantitation ≥ 1.0 g.
• Patients whose has peripheral neuropathy over level 2 in CTC AE4.0, except trauma.
• Patients with respiratory syndrome (difficulty breathing of level 2 or higher ), serous cavity effusion need to surgical treatment ( including pleural of level 2 or higher with respiratory distress and anoxia
• Patients who have unhealed wounds or fractures for a long time.
• Patients with severe infections , and need to receive systemic antibiotic treatment
• Decompensated diabetes or other contraindication with high dose glucocorticoid therapy;
• Cirrhosis or decompensated liver disease; active or untreated hepatitis C and/or Hepatitis B virus (HBV) infection（prior hepatitis B history, HBsAg positive and HBV DNA≥500IU/mL; HCV RNA positive and hepatic Insufficiency
• History of immunodeficiency, HIV infection etc

Sponsors & Collaborators

• Sichuan Cancer Hospital and Research Institute: lead
• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: collaborator

Study Sites (6)

Sichuan Cancer Hospital

Chengdu, Sichuan, 610041, China

RECRUITING

Chengdu fifth people's hospital

Chengdu, China

NOT YET RECRUITING

People's hospital of deyang city

Deyang, China

NOT YET RECRUITING

The affiliated hospital of southwest medical university

Luzhou, China

NOT YET RECRUITING

Nanchong central hospital

Nanchong, China

NOT YET RECRUITING

Suining central hospital

Suining, China

NOT YET RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

anlotinib; Pemetrexed; Cisplatin

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)

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

Study Officials

• ping yu

  Sichuan Cancer Hospital and Research Institute

  PRINCIPAL INVESTIGATOR

• juan li, doctor

  Sichuan Cancer Hospital and Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

juan li

CONTACT

+86 13880276636; dr.lijuan@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of standard treatment department of medical oncology

Study Record Dates

• First Submitted: October 7, 2018
• First Posted: October 15, 2018
• Study Start: December 6, 2018
• Primary Completion: March 10, 2021
• Study Completion: March 10, 2021
• Last Updated: April 6, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)