Non-squamous Non-small-cell Lung CancerPhase 1NCT04012619

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

A Phase 1 study testing Anlotinib Hydrochloride in people with Non-squamous Non-small-cell Lung Cancer and Anlotinib, run by Sichuan University at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Non-squamous Non-small-cell Lung Cancer, Anlotinib
What is being tested?: Anlotinib Hydrochloride
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 8 participants
Where: 1 siteChina
Study dates: 30 Apr 2019to 30 Dec 2020
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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:

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Blood routine examination criteria (no blood transfusion and blood products within 14 days, no correction by G-CSF and other hematopoietic stimuli):
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.

Who cannot join

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;

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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.

Trial locations and contacts

1 site in 1 country.

China1 site

West China Hospital, Sichuan University
Chengdu, Sichuan, 610041

Other trials in China

About this study

Official title: 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.

Read the 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.

Conditions: Non-squamous Non-small-cell Lung Cancer, Anlotinib
Being tested: Anlotinib Hydrochloride

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT04012619
Study group	Role	What they receive
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. Receives: Drug: Anlotinib Hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 1 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Apr 201930 Dec 2020

First posted9 Jul 2019
Study start30 Apr 2019
Primary completion5 Nov 2019
Study completion30 Dec 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Non-squamous Non-small-cell Lung CancerStudies of the same condition, open and under way.
More trials run by Sichuan UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Sequential
Model description: 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.
Masking: None (open label)
Enrolment: 8 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04012619
Sponsor's protocol ID: ALTER-L003
Status last verified: Aug 2023
First submitted: 5 Jul 2019
Last updated: 3 Aug 2023
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
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Patients With Locally Advanced or Metastatic Non-Squamous NSCLC Requiring First-Line Treatment and no Driver Gene Alterations Confirmed by Histology or Cytology
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Non-small Cell Lung Cancer
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A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors
Advanced/Metastatic Solid Tumors, Bladder Cancer

All Non-squamous Non-small-cell Lung Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT04012619
Acronym / sponsor ID: ALTER-L003
Conditions: Non-squamous Non-small-cell Lung Cancer, Anlotinib
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 8 participants (actual)
Lead sponsor: Sichuan UniversityUniversity, hospital or other
Collaborators: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Study start: 30 Apr 2019 (actual)
Primary completion: 5 Nov 2019 (actual)
Study completion: 30 Dec 2020 (actual)
First posted: 9 Jul 2019 (actual)
Results: Posted 3 Aug 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Sequential
Masking: None (open label)
Number of arms: 1
Model description: 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.

Arm	Type	Receives
Anlotinib Hydrochloride Combined With AP	Experimental	Drug: Anlotinib HydrochloridePatients 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.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

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;

Key exclusion criteria (22 listed)

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%;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Anlotinib HydrochlorideAlso: Pemetrexed,cisplatin/carboplatinPatients receive pemetrexed with cisplatin/carboplatin once every 3 weeks, and anlotinib (dose escalation) once daily on days 1-14.	Drug	Anlotinib Hydrochloride Combined With AP

Primary outcome

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.

Results and safety

Results posted to the registry on 3 Aug 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Anlotinib Hydrochloride (12mg) Combined With AP	4	4
Anlotinib Hydrochloride (10mg) Combined With AP	4	4

Primary outcome: the Maximum Tolerated Dose (MTD)

Time frame: 1 month. Number. Unit: mg

Measure	Anlotinib Hydrochloride Combined With AP n = 8
Value	10

Adverse events

Time frame: 12 months. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Anlotinib Hydrochloride (12mg) Combined With AP	2 of 4 (50%)	4 of 4 (100%)	0 of 4
Anlotinib Hydrochloride (10mg) Combined With AP	0 of 4 (0%)	4 of 4 (100%)	0 of 4

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Non-squamous Non-small-cell Lung Cancer

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
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RecruitingObservational study
A Prospective ,Multicenter ,Non-interventional ,Real-world Study Observing Changes in Molecular Markers Osimertinib Targeted Therapy in EGFRm NSCLC
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

You Lu, MD principal investigator

West China Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Anlotinib Hydrochloride in people with Non-squamous Non-small-cell Lung Cancer and Anlotinib, run by Sichuan University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

the Maximum Tolerated Dose (MTD) (time frame: 1 month). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04012619.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2023.