Non-squamous Cell Non-Small Cell Lung CancerPhase 2ALTER-L025NCT03778138
Study of Anlotinib Combined With Pemetrexed in Patients With Advanced Nonsquamous NSCLC
A Phase 2 study testing Anlotinib plus Pemetrexed in people with Non-squamous Cell Non-Small Cell Lung Cancer, run by Henan Provincial People's Hospital at 1 site in China.
Trial summary
In recent years, with the progress in the treatment field, NSCLC has become the most successful cancer species in precision medicine. Patients with positive driving genes such as EGFR, ALK, ROS1, BRAF and so on have clearly targeted drugs, which bring survival benefits to patients.However, about 50% of patients still… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non-squamous Cell Non-Small Cell Lung Cancer
- What is being tested?
- Anlotinib plus Pemetrexed
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2019to 31 Dec 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed the informed consent form prior to patient entry;
- Male or female patients aged 18-75 years old;
- Diagnosed with advanced NSCLC (phase IIIB/IV) through pathology, Neoadjuvant chemotherapy, or postoperative adjuvant chemotherapy or neoadjuvant chemotherapy combined with postoperative adjuvant chemotherapy or targeted chemoradiotherapy for local advanced disease recurrence within 6 months after completion;
- Patients with negative driver genes who had previously only received first-line platinum double-drug therapy progression or intolerance;
- In the past 3 months at least one target lesion that had not previously been irradiated,and at least one direction with the longest diameter at baseline greater than 10 mm (shorter diameter required not less than 15 mm if lymph nodes are involved)could be imaged by CT scan or MRI;
- Expected Survival Time: Over 6 months;
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- had an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1 (on a 5-point scale, with higher scores indicating increasing disability);
- If there is central nervous system metastases,they must be asymptomatic central nervous system metastases;
- The main organs function are normally, the following criteria are met:(1)Blood routine examination criteria should be met (no blood transfusion and blood products within 14 days, no correction by G-CSF and other hematopoietic stimuli): HB≥90 g/L; ANC ≥ 1.5×10^9/L; PLT ≥80×10^9/L;(2)Biochemical examinations must meet the following criteria: TBIL<1.5×ULN; ALT and AST < 2.5×ULN, and for patients with liver metastases < 5×ULN; Serum Cr ≤ 1.25×ULN or endogenous creatinine clearance > 60 ml/min (Cockcroft-Gault formula);
- Women of child-bearing age should take appropriate contraceptive measures and should not breastfeed from screening to 3 months after stopping the study and treatment.Before starting administration, the pregnancy test was negative, or one of the following criteria was met to prove that there was no risk of pregnancy:
- Postmenopause is defined as amenorrhea at least 12 months after age 50 and cessation of all exogenous hormone replacement therapy;
- Postmenopausal women under the age of 50 May also be considered postmenopausal if their amenorrhea is 12 months or more after the cessation of all exogenous hormone therapy and their luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels are within the reference value range of laboratory postmenopausal;
- has undergone irreversible sterilization surgery, including hysterectomy, bilateral ovectomy or bilateral salpingectomy, except for bilateral tubal ligation. For men, consent is required to use appropriate methods of contraception or to be surgically sterilized during the trial and 8 weeks after the last administration of the trial drug.
Who cannot join
- Small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer),Lung sarcomatoid carcinoma;
- Had histologically confirmed lung squamous cell carcinoma, or adenosquamous carcinoma;
- EGFR、ALK mutation-positive by genetic testing technology (pathological examination results of other hospitals are acceptable) and who receive EGFR-TKI and ALK-TKI targeted drug therapy,except EGFR/ALK status cannot be determined for various reasons;
- 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; or there is a significant pulmonary cavity or necrotizing tumor;
- have used Pemetrexed before and progressed;
- Patients with uncontrolled pleural effusion need to be treated with other chemotherapy drugs;
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- Significant weight loss (more than 10% weight loss in the previous 6 weeks);
- Medical history and combined history:
- Had clinically symptomatic central nervous system metastasis(a patient with brain metastases who have completed treatment and stable symptoms in 28 days before enrollment may be enrolled, but should be confirmed by brain MRI, CT or venography evaluation as no cerebral hemorrhage symptoms or metastases in midbrain, pons, cerebellum, medulla oblongata, or spinal cord);
- The patient is participating in other clinical studies or completing the previous clinical study in less than 4 weeks;
- Had malignant tumors except NSCLC within 5 years before enrollment(except for patients with cervical carcinoma in situ , basal cell or squamous cell skin cancer who have undergone a curative treatment, local prostate cancer after radical resection, ductal carcinoma in situ or papillary thyroid cancer after radical resection);
- Patients with previous anti-tumor treatment-related adverse reactions (excluding hair loss) who have not recovered to NCI-CTCAE ≤1;
- 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;Note: Under the premise of prothrombin time international normalized ratio (INR) ≤ 1.5, low-dose heparin (adult daily dose of 0.6 million to 12,000 U) or low-dose aspirin (daily dosage ≤ 100 mg) is allowed for preventive purposes;
- Renal insufficiency: urine routine indicates urinary protein ≥ ++, or confirmed 24-hour urine protein ≥ 1.0g;
- The effects of surgery or trauma have been eliminated for less than 14 days before enrollment in subjects who have undergone major surgery or have severe trauma;
- Severe acute or chronic infections requiring systemic 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%;
- 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;
- Decompensated diabetes or other ailments treated with high doses of glucocorticoids;
- Factors that have a significant impact on oral drug absorption, such as inability to swallow, chronic diarrhea, and intestinal obstruction;
- Clinically significant hemoptysis (daily hemoptysis greater than 2.5ml) 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/venous 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;
- Participated in clinical trials of other antitumor drugs within 4 weeks before enrollment or planned systemic antitumor treatment within 4 weeks before grouping or prior to receiving the test drug including cytotoxic therapy, signal transduction inhibitors, immunotherapy( or use mitomycin C within 6 weeks prior to receiving the test drug).Radiation-rehabilitation radiotherapy (EF-RT) was performed within 4 weeks before grouping or limited-field radiotherapy to be evaluated for tumor lesions within 2 weeks before grouping.
- Physical examination and laboratory findings
- a known history of HIV testing positive or acquired immunodeficiency syndrome (AIDS);
- untreated active hepatitis (hepatitis b: HBsAg positive and HBV DNA more than 1 x 103 copy /ml; Hepatitis c: HCV RNA is positive and liver function is abnormal); Combined with hepatitis b and hepatitis c infection;
- serious diseases that endanger patients' safety or affect patients' completion of research,according to the researchers' judgment.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Henan Provincial People's Hospital
Zhengzhou, Henan, 450000
Cang Shundong, doctor, 0086-13592675836, cangshundong@163.com
About this study
Official title: Study of Anlotinib Combined With Pemetrexed as the Second-line Treatment in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer (ALTER-L025)
In recent years, with the progress in the treatment field, NSCLC has become the most successful cancer species in precision medicine. Patients with positive driving genes such as EGFR, ALK, ROS1, BRAF and so on have clearly targeted drugs, which bring survival benefits to patients.However, about 50% of patients still lack a clear driving gene target, which has become the focus of current research.In the field of wild-type NSCLC with negative driver genes, the classic first-line treatment regimen is the two-drug regimen containing platinum.he phase II clinical study of pemetrexed in the second-line treatment of advanced non-small cell lung cancer patients with pemetrexed versus carboplatin pemetrexed showed that the median PFS time in the pemetrexed group was 3.5 months.
Anlotinib is a multi-target receptor tyrosine kinase inhibitor in domestic research and development.In the phase Ⅲ study, patients who failed at least two kinds of systemic chemotherapy (third line or beyond) or drug intolerance were treated with anlotinib or placebo, the anlotinib group PFS and OS were 5.37 months and 9.63 months, the placebo group PFS and OS were 1.4 months and 6.3 months.
The efficacy and safety of anrotinib combined with pemetrexed in the second-line treatment of advanced non-squamous and non-small cell patients deserve further exploration.
Read the detailed description
This is a multicentre single arm clinical trial conducted in China,the purpose of this study is to evaluate and observe Anlotinib (12mg QD PO d1-14, 21 days per cycle) Combined With Pemetrexed(500mg/m2,IV,d1,21 days per cycle) as the second-line Treatment in Patients With Advanced nonsquamous Non-Small-Cell Lung Cancer.As the report,The median PFS of advanced NSCLC treated by Pemetrexed as second-line was 3-3.5 months.We expect the median PFS of Anlotinib combined with Pemetrexed as the second-line Treatment in Patients With Advanced nonsquamous NSCLC was 6 months.Using PASS15, we calculated the sample size of this study was 46(α=0.025、β=0.1), according to 10% censoring,the expected sample size is 51.
- Being tested
- Anlotinib plus Pemetrexed
- Keywords
- Advanced nonsquamous Non-Small Cell Lung Cancer, Anlotinib Combined With Pemetrexed
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anlotinib plus PemetrexedDrug
Anlotinib(12mg QD PO d1-14, 21 days per cycle) plus Pemetrexed (500mg/m2 IV d1)
| Study group | Role | What they receive |
|---|---|---|
| Anlotinib plus Pemetrexed | Experimental | Anlotinib(12mg QD PO d1-14, 21 days per cycle) plus Pemetrexed (500mg/m2 IV d1) Receives: Drug: Anlotinib plus Pemetrexed |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progress free survival (PFS) based on investigator assessment
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.
Measured: each 42 days up to PD or death(up to 24 months)
Secondary outcomes (4)
Objective Response Rate based on investigator assessment
ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.prior to progression or any further therapy.
Measured: each 42 days up to intolerance the toxicity or PD (up to 24 months)
Disease Control Rate(DCR)
Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.
Measured: each 42 days up to intolerance the toxicity or PD (up to 24 months)
Overall Survival(OS)
Defined as the time until death due to any cause.
Measured: each 42 days up to intolerance the toxicity or PD (up to 24 months) .
Safety(Number of Participants with Adverse Events and Clinical laboratory numerical evaluation as a Measure of Safety)
Number of Participants with Adverse Events and Clinical laboratory numerical evaluation as a Measure of Safety
Measured: each 42 days up to intolerance the toxicity or PD (up to 24 months) .
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2018
- Study start1 Jan 2019 (estimated)
- Primary completion31 Dec 2019 (estimated)
- Study completion31 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-squamous Cell Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Anlotinib and Pemetrexed
- Masking
- None (open label)
- Enrolment
- 51 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Henan Provincial People's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- Cang Shundong, doctor, Principal investigator, Henan Provincial People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03778138
- Sponsor's protocol ID
- ALTER-L025
- Acronym
- ALTER-L025
- Status last verified
- Dec 2018
- First submitted
- 14 Dec 2018
- Last updated
- 19 Dec 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Anlotinib Combined With Pemetrexed as the Second-line Treatment in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer (ALTER-L025)
- ClinicalTrials.gov ID
- NCT03778138
- Acronym / sponsor ID
- ALTER-L025 / ALTER-L025
- Keywords
- Advanced nonsquamous Non-Small Cell Lung Cancer, Anlotinib Combined With Pemetrexed
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 51 participants (estimated)
- Lead sponsor
- Henan Provincial People's HospitalUniversity, hospital or other
- Collaborators
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Study start
- 1 Jan 2019 (estimated)
- Primary completion
- 31 Dec 2019 (estimated)
- Study completion
- 31 Dec 2020 (estimated)
- First posted
- 19 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In recent years, with the progress in the treatment field, NSCLC has become the most successful cancer species in precision medicine. Patients with positive driving genes such as EGFR, ALK, ROS1, BRAF and so on have clearly targeted drugs, which bring survival benefits to patients.However, about 50% of patients still lack a clear driving gene target, which has become the focus of current research.In the field of wild-type NSCLC with negative driver genes, the classic first-line treatment regimen is the two-drug regimen containing platinum.he phase II clinical study of pemetrexed in the second-line treatment of advanced non-small cell lung cancer patients with pemetrexed versus carboplatin pemetrexed showed that the median PFS time in the pemetrexed group was 3.5 months.
Anlotinib is a multi-target receptor tyrosine kinase inhibitor in domestic research and development.In the phase Ⅲ study, patients who failed at least two kinds of systemic chemotherapy (third line or beyond) or drug intolerance were treated with anlotinib or placebo, the anlotinib group PFS and OS were 5.37 months and 9.63 months, the placebo group PFS and OS were 1.4 months and 6.3 months.
The efficacy and safety of anrotinib combined with pemetrexed in the second-line treatment of advanced non-squamous and non-small cell patients deserve further exploration.
Detailed description
This is a multicentre single arm clinical trial conducted in China,the purpose of this study is to evaluate and observe Anlotinib (12mg QD PO d1-14, 21 days per cycle) Combined With Pemetrexed(500mg/m2,IV,d1,21 days per cycle) as the second-line Treatment in Patients With Advanced nonsquamous Non-Small-Cell Lung Cancer.As the report,The median PFS of advanced NSCLC treated by Pemetrexed as second-line was 3-3.5 months.We expect the median PFS of Anlotinib combined with Pemetrexed as the second-line Treatment in Patients With Advanced nonsquamous NSCLC was 6 months.Using PASS15, we calculated the sample size of this study was 46(α=0.025、β=0.1), according to 10% censoring,the expected sample size is 51.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Anlotinib and Pemetrexed
| Arm | Type | Receives |
|---|---|---|
| Anlotinib plus Pemetrexed | Experimental | Drug: Anlotinib plus PemetrexedAnlotinib(12mg QD PO d1-14, 21 days per cycle) plus Pemetrexed (500mg/m2 IV d1) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Signed the informed consent form prior to patient entry;
- Male or female patients aged 18-75 years old;
- Diagnosed with advanced NSCLC (phase IIIB/IV) through pathology, Neoadjuvant chemotherapy, or postoperative adjuvant chemotherapy or neoadjuvant chemotherapy combined with postoperative adjuvant chemotherapy or targeted chemoradiotherapy for local advanced disease recurrence within 6 months after completion;
- Patients with negative driver genes who had previously only received first-line platinum double-drug therapy progression or intolerance;
- In the past 3 months at least one target lesion that had not previously been irradiated,and at least one direction with the longest diameter at baseline greater than 10 mm (shorter diameter required not less than 15 mm if lymph nodes are involved)could be imaged by CT scan or MRI;
Key exclusion criteria (29 listed)
- Small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer),Lung sarcomatoid carcinoma;
- Had histologically confirmed lung squamous cell carcinoma, or adenosquamous carcinoma;
- EGFR、ALK mutation-positive by genetic testing technology (pathological examination results of other hospitals are acceptable) and who receive EGFR-TKI and ALK-TKI targeted drug therapy,except EGFR/ALK status cannot be determined for various reasons;
- 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; or there is a significant pulmonary cavity or necrotizing tumor;
- have used Pemetrexed before and progressed;
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 plus PemetrexedAnlotinib(12mg QD PO d1-14, 21 days per cycle) plus Pemetrexed (500mg/m2 IV d1) | Drug | Anlotinib plus Pemetrexed |
Primary outcome
Progress free survival (PFS) based on investigator assessment
Time frame: each 42 days up to PD or death(up to 24 months)
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.
4 secondary outcomes
Objective Response Rate based on investigator assessment
Time frame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
Disease Control Rate(DCR)
Time frame: each 42 days up to intolerance the toxicity or PD (up to 24 months)
Overall Survival(OS)
Time frame: each 42 days up to intolerance the toxicity or PD (up to 24 months) .
Safety(Number of Participants with Adverse Events and Clinical laboratory numerical evaluation as a Measure of Safety)
Time frame: each 42 days up to intolerance the toxicity or PD (up to 24 months) .
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2018.
- Individual participant dataSharing planned: No
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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.
Cang Shundong, doctor principal investigator
Henan Provincial People's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Anlotinib plus Pemetrexed in people with Non-squamous Cell Non-Small Cell Lung Cancer, run by Henan Provincial People's Hospital 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 13 inclusion and 29 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: status not confirmed, as of the sponsor's last update on 19 Dec 2018. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Cang Shundong, doctor (0086-13592675836, cangshundong@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progress free survival (PFS) based on investigator assessment (time frame: each 42 days up to PD or death(up to 24 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Dec 2018.