Pemetrexed and Carboplatin With or Without Anlotinib Hydrochloride for Osimertinib-resistant Non-squamous NSCLC

NCT04136535 | Recruiting Phase 2

• 1 other identifier: ALTER-L031
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

Brief Summary

Evaluate the efficacy and safety of Anlotinib Hydrochloride in combination with Pemetrexed and Carboplatin versus Pemetrexed and Carboplatin for advanced or locally-advanced Osimertinib-resistant non-squamous non-small cell lung cancer.

Conditions

NSCLC Stage IV

Outcome Measures

Primary Outcomes (1)

• PFS

  Progress 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 18 months

Study Arms (2)

Pemetrexed and Carboplatin with Anlotinib

EXPERIMENTAL

Pemetrexed and Carboplatin with Anlotinib

Drug: Pemetrexed; Drug: Carboplatin; Drug: Anlotinib

Pemetrexed and Carboplatin without Anlotinib

ACTIVE COMPARATOR

Pemetrexed and Carboplatin without Anlotinib

Drug: Pemetrexed; Drug: Carboplatin

Interventions

Pemetrexed DRUG

Pemetrexed，500mg/m²，ivgtt ，d1，q3w

Pemetrexed and Carboplatin with Anlotinib; Pemetrexed and Carboplatin without Anlotinib

Carboplatin DRUG

Carboplatin，AUC 5.0，ivgtt，d1，q3w，

Pemetrexed and Carboplatin with Anlotinib; Pemetrexed and Carboplatin without Anlotinib

Anlotinib DRUG

Anlotinib ，12 mg，po，qd，d1-14，q3w；

Pemetrexed and Carboplatin with Anlotinib

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 Years to 75 Years patients voluntarily participate in this study, signed and dated informed consent with good compliance and follow-up; 2. Confirmed as locally advanced and / or metastatic non-squamous non-small cell lung cancer (NSCLC) by cytology or histology, the diagnosis should be completed at least 6 months after the end of chemotherapy if adjuvant chemotherapy and / or neoadjuvant chemotherapy received (diagnosis based on sputum smear is not accepted) ; 3. Presence of EGFR activating mutations and previously disease progression to Osimertinib (previously treated with 1st / 2nd generation EGFR-TKI or not)； 4. At least one target lesion that has accurate measurement by magnetic resonance imaging (MRI) or computed tomography (CT) (conventional CT≥20 mm or spiral CT≥10 mm) in at least 1 direction; 5. Life expectancy is at least 3 months; 6. ECOG PS Scoring: 0\~1 point; 8. The main organs function are normally, the following criteria are met:
• Blood routine examination criteria (no blood transfusion and blood products within 14 days, no correction by G-CSF and other hematopoietic stimuli):
• i) hemoglobin (HB) ≥90g/L ii) neutrophil absolute (ANC) ≥1.5×109/L iii) platelet (PLT) ≥80×109/L Biochemical tests meet the following criteria i) total bilirubin (TBIL) ≤1.5 times of upper limit of normal (ULN); ii) alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤2.5 ULN, if liver metastasis occurred, ALT and AST ≤5 ULN; iii) serum creatinine (Cr) ≤1.25 ULN or creatinine clearance (CCr)≥45mL/min (Cockcroft-Gault formula).
• Female patients of childbearing age agree that contraceptive measures must be used within the study period and within 8 weeks after the end of the study drug treatment. The serum or urine test indicates unpregnancy within 7 days prior to the study. Male patients agree to have contraceptive use during the study period and within 8 weeks after the end of the study period or have had surgical sterilization.

You may not qualify if:

• Patients with small cell lung cancer (including small cell carcinoma and non-small cell carcinoma mixed lung cancer) and lung adenosquamous carcinoma mixed with squamous carcinoma;
• Active brain metastases, cancerous meningitis, spinal cord compression, or imaging CT or MRI screening for brain or pia mater disease (a patient with brain metastases who have completed treatment and stable symptoms in 21 days before enrollment may be enrolled, but should be confirmed by brain MRI, CT or venography evaluation as no cerebral hemorrhage symptoms);
• Imaging (CT or MRI) shows that the distance between tumor lesion and the large blood vessel is ≤ 5 mm, or there is a central tumor that invades the local large blood vessel and the distance between tumor and bronchial tree is ≤ 2 cm; or there is a significant pulmonary cavity or necrotizing tumor;
• Uncontrollable hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg after optimal medical treatment);
• Suffering from severe cardiovascular disease: myocardial ischemia or myocardial infarction above grade II, poorly controlled arrhythmias (including men with QTc interval ≥ 450 ms, women ≥ 470 ms); according to NYHA criteria, grades III to IV Insufficient function, or cardiac color Doppler ultrasound examination indicates left ventricular ejection fraction (LVEF) \<50%;
• Abnormal blood coagulation (INR \> 1.5 or prothrombin time (PT) \> ULN + 4 seconds or APTT \> 1.5 ULN), with bleeding tendency or undergoing thrombolytic or anticoagulant therapy;
• Urine routine test protein ≥++, and confirmed 24 hours urine protein\> 1.0 g;
• There is currently a peripheral neuropathy of ≥CTCAE 2 degrees, except for trauma;
• Respiratory syndrome (≥CTC AE grade 2 dyspnea), serous effusion (including pleural effusion, ascites, pericardial effusion) requiring surgical treatment;
• Long-term unhealed wounds or fractures;
• Serious infection (≥CTC AE Level 2 infection) requiring systemic antibiotics;
• decompensated diabetes or other ailments treated with high doses of glucocorticoids;
• Active or chronic hepatitis C or/and hepatitis B infection;
• Factors that have a significant impact on oral drug absorption, such as inability to swallow, chronic diarrhea, and intestinal obstruction;
• Patients have undergone major surgery within 4 weeks before enrollment or have severe trauma, fracture and ulcer;

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Caner hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Uninon Medical college

Shenzhen, shenzhen, 518116, China

RECRUITING

Related Publications (1)

• Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. doi: 10.1056/NEJMoa1612674. Epub 2016 Dec 6.

  PMID: 27959700 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Pemetrexed; Carboplatin; anlotinib

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; Coordination Complexes; Organic Chemicals

Study Officials

• chang j hua, PD

  PI

  PRINCIPAL INVESTIGATOR

Central Study Contacts

chang J hua, PD

CONTACT

18017312689; changjianhua@163.com

xiang h wu, dorctor

CONTACT

13482888167; xhwu2011@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: primary care physician

Study Record Dates

• First Submitted: October 14, 2019
• First Posted: October 23, 2019
• Study Start: November 18, 2021
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: July 22, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)