Anlotinib Hydrochloride Combined With AP in Stage IIIB/IIIC/IV Non-squamous Non-small-cell Lung Cancer

NCT04012619 | Completed Phase 1 Results

• 1 other identifier: ALTER-L003
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Anlotinib is a novel oral multitarget tyrosine kinase inhibitor and primary targeted to VEGFR, FGFR, PDGFR and c-Kit. The ALTER-0303 trial showed that patients with advanced non-small cell lung cancer (NSCLC) who received anlotinib as third-line or further therapy had more survival benefit. Pemetrexed plus platinum-based chemotherapy (AP) was long considered as the first line treatment in non-squamous NSCLC patients with negative driver mutation. In this dose exploration study, the primary objective is to establish the safety profile of anlotinib combined with AP in non-squamous NSCLC patients by identifying dose limiting toxicity (DLT), maximum tolerance dose (MTD), the recommended phase II dose, and schedule. Secondary objective includes the assessment of preliminary antitumor effect.

Conditions

Non-squamous Non-small-cell Lung Cancer; Anlotinib

Outcome Measures

Primary Outcomes (1)

• the Maximum Tolerated Dose (MTD)

  The primary endpoint was the MTD of anlotinib, at which less than 33% of patients experienced a DLT in the frst treatment cycle. A DLT involving hematological toxicity was defned as grade 4 and above, non-hematological toxicity as grade 3 and above, and liver and kidney function injury as grade 2 and above.

  1 month

Study Arms (1)

Anlotinib Hydrochloride Combined With AP

EXPERIMENTAL

Patients receive pemetrexed (500mg/m2) with cisplatin (75mg/m2)/carboplatin (area under the curve 5) once every 3 weeks, and anlotinib (dose escalation) once daily on days 1-14 of a 21-day cycle. Anlotinib with AP will be administrated up to 4 cycles followed by maintenance treatment with anlotinib once daily (12mg/d) on days 1-14 of a 21-day cycle until disease progression or treatment intolerance.

Drug: Anlotinib Hydrochloride

Interventions

Anlotinib Hydrochloride DRUG

Patients receive pemetrexed with cisplatin/carboplatin once every 3 weeks, and anlotinib (dose escalation) once daily on days 1-14.

Also known as: Pemetrexed,cisplatin/carboplatin

Anlotinib Hydrochloride Combined With AP

Eligibility Criteria

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

You may qualify if:

• Years to 75 Years patients voluntarily participate in this study, signed and dated informed consent with good compliance and follow-up;
• Diagnosed as locally advanced and / or metastatic non-squamous non-small cell lung adenocarcinoma (NSCLC) by cytology or histology; Provide detectable specimens (tissue or blood) for genotyping before enrollment, and the patients should be with negative EGFR, ALK and ROS1 gene test results, and without prior systemic therapy;
• At least one target lesion that has not received radiotherapy, and 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;
• Life expectancy is at least 3 months;
• ECOG PS Scoring: 0\~1 point;
• 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;
• Severe weight loss (greater than 10%) within 6 weeks prior to enrollment;

Sponsors & Collaborators

• Sichuan University: lead
• Chia Tai Tianqing Pharmaceutical Group Co., Ltd.: collaborator

Study Sites (1)

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

MeSH Terms

Interventions

Pemetrexed

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

Results Point of Contact

• Title: Prof. You Lu
• Organization: West China Hospital, Sichuan University

radyoulu@hotmail.com

13398179653

Study Officials

• You Lu, MD

  West China Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair of Department of Thoracic Cancer

Model Details: The initial dose of anlotinib was set as 12 mg/day with a 2-week on/1-week of schedule. The dose was reduced to 10 mg/day and 8 mg/day in sequence depending on observed DLTs in cycle 1.

Study Record Dates

• First Submitted: July 5, 2019
• First Posted: July 9, 2019
• Study Start: April 30, 2019
• Primary Completion: November 5, 2019
• Study Completion: December 30, 2020
• Last Updated: August 3, 2023
• Results First Posted: August 3, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)