- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04012619
Anlotinib Hydrochloride Combined With AP in Stage IIIB/IIIC/IV Non-squamous Non-small-cell Lung Cancer
August 2, 2023 updated by: You Lu, Sichuan University
Safety and Efficacy of Anlotinib Hydrochloride Combined With Pemetrexed Plus Cisplatin/Carboplatin (AP) as First Line Treatment for Stage IIIB/IIIC/IV Non-squamous Non-small-cell Lung Cancer
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Anlotinib, a new small molecule inhibitor of multiple receptor tyrosine kinases targeting the vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit,8,9 has been approved as a third-line treatment for refractory advanced NSCLC by the China Food and Drug Administration (CFDA) on May 9, 2018.10
Previous study in phase II (ALTER0302) trial has shown a better progression-free survival (PFS) in advanced NSCLC patients treated with anlotinib compared those with the placebo (4.8 vs 1.2 months, P<0.0001).11
In phase III (ALTER0303) trial, both the overall survival (OS) and PFS of advanced NSCLC patients were observed to be significantly longer in the anlotinib group (median, 9.6 and 5.4 months) than the placebo group (median, 6.3 and 1.4 months).12
Moreover, anlotinib also displayed manageable toxicity, long circulation, and broad-spectrum antitumor potential.13,14
For the lack of recommended drugs with exactly therapeutic effect in the third-line treatment of SCC patients, it is worth to further analyze the efficacy and specifically clinical observation indicator of anlotinib in this subtype of NSCLC patients.
In this dose exploration study, the primary objective is to establish the safety profile of anlotinib combined with AP in treatment-naive 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.
Study Type
Interventional
Enrollment (Actual)
8
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Sichuan
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Chendu, Sichuan, China, 610041
- West China Hospital, Sichuan University
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- 18 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.
Exclusion Criteria:
- 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;
- Clinically significant hemoptysis (daily hemoptysis greater than 50ml) within 3 months prior to enrollment; or significant clinically significant bleeding symptoms or defined bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood ++ and above, or suffering from vasculitis;
- Events of venous/ arterious thrombosis occurring within the first 12 months prior to enrollment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
- Patients have contraindication to platinum drugs (cisplatin/carboplatin) and cytotoxic drug (Pemetrexed);
- Patients have anaphylactic reaction due to anlotinib Hydrochloride or the excipient in investigational drug.
- Patients have anaphylactic reaction due to contrast agent;
- Planned for systemic anti-tumor therapy during the study period or within 4 weeks prior to enrollment, including cytotoxic therapy, signal transduction inhibitors, immunotherapy (or use mitomycin C within 6 weeks prior to receiving investigational drug). Radiation-rehabilitation radiotherapy (EF-RT) was performed within 4 weeks before enrollment or limited-field radiotherapy was performed for planned tumor lesions within 2 weeks before enrollment.
- Patients were diagnosed with disease which will severely endanger the security of patients or influence the completion of this research, or patients with other situations are not suitable for the study according to the researchers.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Anlotinib Hydrochloride Combined With AP
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.
|
Patients receive pemetrexed with cisplatin/carboplatin once every 3 weeks, and anlotinib (dose escalation) once daily on days 1-14.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
the Maximum Tolerated Dose (MTD)
Time Frame: 1 month
|
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
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: You Lu, MD, West China Hospital
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
April 30, 2019
Primary Completion (Actual)
November 5, 2019
Study Completion (Actual)
December 30, 2020
Study Registration Dates
First Submitted
July 5, 2019
First Submitted That Met QC Criteria
July 5, 2019
First Posted (Actual)
July 9, 2019
Study Record Updates
Last Update Posted (Actual)
August 3, 2023
Last Update Submitted That Met QC Criteria
August 2, 2023
Last Verified
August 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antineoplastic Agents
- Folic Acid Antagonists
- Carboplatin
- Cisplatin
- Pemetrexed
Other Study ID Numbers
- ALTER-L003
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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