Non-squamous Non-small Cell Lung CancerNCT03566576
Phase I Study of the Combination of Anlotinib With Pemetrexed or Docetaxel
A study testing Anlotinib, Pemetrexed and Docetaxel in people with Non-squamous Non-small Cell Lung Cancer, run by Fujian Cancer Hospital.
Trial summary
The purpose of this clinical study is to evaluate the tolerability and toxicity of different dose of Anlotinib puls Pemetrexed/Docetaxel in Second-line Treatment of Advanced Gene Negative Non-squamous Non-small Cell Lung Cancer , to provide a reference of dosage for Phase II clinical trials Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Non-squamous Non-small Cell Lung Cancer
- What is being tested?
- Anlotinib, Pemetrexed and Docetaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- No sites listed yet
- Study dates
- 1 Jul 2018to 1 Oct 2018
- Phase
- Interventional
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be≥18 years of age on the day of signing informed consent.
- Patients with histologic or cytologic confirmation of advanced or metastatic NSCLC with stage III or IV disease amenable to platinum-based chemotherapy were assessed for eligibility.
- Patients with EGFR、ALK、ROS1 Mutation-negative were eligible.
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status.
- Life expectancy ≥3 months.
- Without serious system dysfunction and could tolerate chemotherapy.
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- With normal marrow, liver ,renal and coagulation function:
- a leucopenia count of ≥3.0×109/L; a platelet count of ≥1.5×109/L; hemoglobin≥ 90 g/L; a platelet count of ≥100×109/L; a alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) of ≤2.5 UNL in case of liver metastasis; a total bilirubin (TBil) of ≤1.5 upper normal limitation (UNL); a creatinine (Cr) of ≤ 1.5 UNL; a creatinine clearance rate ≥ 50ml/min (Cockcroft-Gault);
- With normal coagulation function: activated partial thromboplastin time (APTT), prothrombin time (PT) and INR, each ≤ 1.5 x UNL.
- Female subjects of child-bearing potential must agree to use contraceptive measures starting 1 week before the administration of the first dose of apatinib until 8 weeks after discontinuing study drug. Male subjects must agree to use contraceptive measures during the study and 8 weeks after last dose of study drug.
- With written informed consent signed voluntarily by patients themselves or their supervisors witted by doctors.
- With good compliance and agree to accept follow-up of disease progression and adverse events.
Who cannot join
- Small cell lung cancer (include Small cell lung cancer mixture of NSCLC).
- Patients with brain or central nervous system metastases, including leptomeningeal disease, or CT/MRI examination revealed brain or leptomeningeal disease） (14 days before the random treatment has been completed and the symptoms of patients with brain metastases from stable can into the group, but need to the cerebral MRI, CT or vein angiography confirmed as without symptoms of cerebral hemorrhage).
- Iconography (CT or MRI) shows that the tumor vessels have 5 mm or less, or Cardiovascular involvement by Central tumor ; Or obvious lung empty or necrotic tumor.
- Uncontrollable hypertensive (systolic blood pressure or greater 140 mmHg or diastolic blood pressure or greater 90 mmHg, despite the best drug treatment).
- Significant cardiac disease as defined as: grade II or greater myocardial infarction, unstable arrhythmia(Including corrected QT interval (QTc )period between male or greater 450 ms, female or greater 470 ms); New York Heart Association (NYHA) grade II or greater heart dysfunction , or Echocardiography reveal left ventricular ejection fraction （LVEF）Less than 50%.
- Abnormal coagulation (INR > 1.5 or prothrombin time (PT) > ULN + 4 seconds or APTT ULN > 1.5), with bleeding tendency or be treated with thrombolysis and anticoagulation.
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- Note: under the premise of International Normalized ratio (INR) of prothrombin time (PT) Less than or equal to 1.5, allow to administrate low-dose heparin (adult daily dose is 06000 ~ 12000 U) or low-dose aspirin (100 mg daily dosage or less) , for prophylactic purposes.
- Urine routines show urine protein≥ ++, or urine protein quantity≥ 1.0 g during 24 hours.
- Patients with NCI-CTCAE grade II or greater peripheral neuropathy, except due to trauma.
- Clinically significant serous effusion (including pleural effusion, ascites, pericardial effusion).
- Serious, non-healing wound, ulcer, or bone fracture.
- Patients with severe infections , and need to receive Systemic antibiotic treatment.
- Decompensated diabetes or high dose glucocorticoid treatment of other contraindication.
- Active or chronic hepatitis c and/or Hepatitis B virus (HBV) infection.
- Has an obvious factor influencing oral drug absorption, such as unable to swallow, chronic diarrhea and intestinal obstruction, etc.
- Has received major surgery or severe traumatic injury, fractures or ulcer Within 4weeks before Random.
- Severe weight loss (> 10%) Within 6 weeks before Random.
- Has Clinically significant hemoptysis Within 3 months before Random (daily hemoptysis than 50 ml;Or significant clinical significance of bleeding symptoms or have definite bleeding tendency, such as gastrointestinal bleeding, bleeding ulcers, baseline period + + and above of fecal occult blood, or vasculitis, etc.
- Has venous thromboembolism events Within 12 months before Random, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, etc.
- There are any contraindications with receiving pemetrexed or docetaxel treatment; has a history of severe allergic reactions of docetaxel or other containing Polysorbate 80 (twain 80)
- There are allergic reaction to contrast media, anlotinib, and/or excipient of experimental drug.
- Patients with any other medical condition or reason, in that investigator's opinion, makes the patient unstable to participate in a clinical trial.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Dose Climbing Trial of Anlotinib Plus Pemetrexed/Docetaxel in the Second-line Treatment of Advanced Gene Negative Non-squamous Non-small Cell Lung Cancer
The purpose of this clinical study is to evaluate the tolerability and toxicity of different dose of Anlotinib puls Pemetrexed/Docetaxel in Second-line Treatment of Advanced Gene Negative Non-squamous Non-small Cell Lung Cancer , to provide a reference of dosage for Phase II clinical trials
Read the detailed description
This is a randomized, single -center study conducted in China to compare the tolerability and toxicity of different dose of Anlotinib Plus Pemetrexed / Docetaxel in patients of Advanced Gene Negative Non-squamous Non-small Cell Lung Cancer.From low dose group up to high dose group, each one had 3 patients at least.Primary group received anlotinib 8mg. The dose of Anlotinib would increase gradually until MTD.
Eligible patients will be randomized to arm A and arm B:
Arm A: Patients were instructed to take folic acid 400ug orally daily beginning 1 week before the first dose of pemetrexed and continuing daily until 3 weeks after the last dose of pemetrexed. A 1000ug B12 injection was administered intramuscularly approximately 1 week before the first dose of pemetrexed and was repeated approximately every 9 weeks until after discontinuation. All target volumes were instructed to take dexamethasone (4 mg orally twice daily the day before, the day of, and the day after pemetrexed) as a prophylactic measure against skin rash. Patients on the pemetrexed arm received 500mg/m2 pemetrexed as a 10-minute intravenous infusion on day 1 of a 21-day cycle and 8mg/10mg/12mg Anlotinib orally daily on day 1 to 14 of a 21-day cycle.
Arm B: Patients on the docetaxel arm received 60mg/m2 docetaxel as a 10-minute intravenous infusion on day 1 of a 21-day cycle and 8mg/10mg/12mg anlotinib orally daily on day 1to 14 of a 21-day cycle.
Approximately 18 patients will be enrolled to ensure that roughly 9 patients per arm complete treatments for primary endpoint analysis.
- Conditions
- Non-squamous Non-small Cell Lung Cancer
- Being tested
- Anlotinib, Pemetrexed, Docetaxel
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnlotinibDrug
Anlotinib 8mg p.o. qd in first cohort (3 subjects). 10mg p.o. qd in second cohort (3 subjects). 12mg p.o. qd in third cohort (3 subjects).
PemetrexedDrug
Pemetrexed 500mg/m2 as a 10-minute intravenous infusion on day 1 of a 21-day cycle.
DocetaxelDrug
Also called Taxotere
Docetaxel 60mg/m2 as a 10-minute intravenous infusion on day 1 of a 21-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Anlotinib Plus Pemetrexed | Experimental | This study will include a sequential evaluation of 3 subjects per cohort. Cohort 1: Anlotinib 8mg per day and Pemetrexed. Cohort 2: Anlotinib 10mg per day and Pemetrexed. Cohort 3: Anlotinib 12mg per day and Pemetrexed.
A dose limiting toxicity (DLT) event is defined as any of the following events:
1. CTCAE Grade 4 event (ANC<1000/ul, body temperature≥38.5°C);
2. Grade 3 non-hematologic toxicity (except for nausea and vomiting that could be improved with optimal supportive care, escalation of alkaline phosphatase) If a DLT is experienced in any cohort, the cohort will be expanded to 6 subjects. If 2 DLTs are experienced in any cohort, the dose escalation ceased. The MTD was defined as the dose having at most two out of six patients experience DLT. Receives: Drug: Anlotinib; Drug: Pemetrexed |
| Anlotinib Plus Docetaxel | Experimental | This study will include a sequential evaluation of 3 subjects per cohort. Cohort 1: Anlotinib 8mg per day and Pemetrexed. Cohort 2: Anlotinib 10mg per day and Pemetrexed. Cohort 3: Anlotinib 12mg per day and Pemetrexed.
A dose limiting toxicity (DLT) event is defined as any of the following events:
1. CTCAE Grade 4 event (ANC<1000/ul, body temperature≥38.5°C);
2. Grade 3 non-hematologic toxicity (except for nausea and vomiting that could be improved with optimal supportive care, escalation of alkaline phosphatase) If a DLT is experienced in any cohort, the cohort will be expanded to 6 subjects. If 2 DLTs are experienced in any cohort, the dose escalation ceased. The MTD was defined as the dose having at most two out of six patients experience DLT. Receives: Drug: Anlotinib; Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicity
Dose Limiting Toxicity (DLT) is referred to grade 3 non-hematological toxicity or grade 4 hematological toxicity according to NCI CTCAE 4.03 criteria
Measured: From enrollment to completion of study. Estimated about 6 months.
Maximum tolerance dose
Maximum Tolerance Dose (MTD) is the dose of treatment in the cohort where there are 2 cases of DTL reported.
Measured: From enrollment to completion of study. Estimated about 6 months
Secondary outcomes (2)
disease control rate
Clinical response of treatment according to RESIST v1.1 criteria (DCR, disease control rate)
Measured: From enrollment to 2 months after treatment
time to progression
The length of time from enrollment until the time of progression of disease (TTP, time to progression).
Measured: From enrollment to progression of disease. Estimated about 6 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2018
- Study start1 Jul 2018 (estimated)
- Primary completion1 Sep 2018 (estimated)
- Study completion1 Oct 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-squamous Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Fujian Cancer HospitalThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fujian Cancer Hospital
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Lin Gen, Principal investigator, Fujian Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03566576
- Sponsor's protocol ID
- FujianCH110
- Status last verified
- May 2018
- First submitted
- 29 May 2018
- Last updated
- 25 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose Climbing Trial of Anlotinib Plus Pemetrexed/Docetaxel in the Second-line Treatment of Advanced Gene Negative Non-squamous Non-small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT03566576
- Acronym / sponsor ID
- FujianCH110
- Conditions
- Non-squamous Non-small Cell Lung Cancer
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Fujian Cancer HospitalOther government
- Study start
- 1 Jul 2018 (estimated)
- Primary completion
- 1 Sep 2018 (estimated)
- Study completion
- 1 Oct 2018 (estimated)
- First posted
- 25 Jun 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.
The purpose of this clinical study is to evaluate the tolerability and toxicity of different dose of Anlotinib puls Pemetrexed/Docetaxel in Second-line Treatment of Advanced Gene Negative Non-squamous Non-small Cell Lung Cancer , to provide a reference of dosage for Phase II clinical trials
Detailed description
This is a randomized, single -center study conducted in China to compare the tolerability and toxicity of different dose of Anlotinib Plus Pemetrexed / Docetaxel in patients of Advanced Gene Negative Non-squamous Non-small Cell Lung Cancer.From low dose group up to high dose group, each one had 3 patients at least.Primary group received anlotinib 8mg. The dose of Anlotinib would increase gradually until MTD.
Eligible patients will be randomized to arm A and arm B:
Arm A: Patients were instructed to take folic acid 400ug orally daily beginning 1 week before the first dose of pemetrexed and continuing daily until 3 weeks after the last dose of pemetrexed. A 1000ug B12 injection was administered intramuscularly approximately 1 week before the first dose of pemetrexed and was repeated approximately every 9 weeks until after discontinuation. All target volumes were instructed to take dexamethasone (4 mg orally twice daily the day before, the day of, and the day after pemetrexed) as a prophylactic measure against skin rash. Patients on the pemetrexed arm received 500mg/m2 pemetrexed as a 10-minute intravenous infusion on day 1 of a 21-day cycle and 8mg/10mg/12mg Anlotinib orally daily on day 1 to 14 of a 21-day cycle.
Arm B: Patients on the docetaxel arm received 60mg/m2 docetaxel as a 10-minute intravenous infusion on day 1 of a 21-day cycle and 8mg/10mg/12mg anlotinib orally daily on day 1to 14 of a 21-day cycle.
Approximately 18 patients will be enrolled to ensure that roughly 9 patients per arm complete treatments for primary endpoint analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Anlotinib Plus Pemetrexed | Experimental | Drug: Anlotinib, Drug: PemetrexedThis study will include a sequential evaluation of 3 subjects per cohort. Cohort 1: Anlotinib 8mg per day and Pemetrexed. Cohort 2: Anlotinib 10mg per day and Pemetrexed. Cohort 3: Anlotinib 12mg per day and Pemetrexed. A dose limiting toxicity (DLT) event is defined as any of the following events: 1. CTCAE Grade 4 event (ANC<1000/ul, body temperature≥38.5°C); 2. Grade 3 non-hematologic toxicity (except for nausea and vomiting that could be improved with optimal supportive care, escalation of alkaline phosphatase) If a DLT is experienced in any cohort, the cohort will be expanded to 6 subjects. If 2 DLTs are experienced in any cohort, the dose escalation ceased. The MTD was defined as the dose having at most two out of six patients experience DLT. |
| Anlotinib Plus Docetaxel | Experimental | Drug: Anlotinib, Drug: DocetaxelThis study will include a sequential evaluation of 3 subjects per cohort. Cohort 1: Anlotinib 8mg per day and Pemetrexed. Cohort 2: Anlotinib 10mg per day and Pemetrexed. Cohort 3: Anlotinib 12mg per day and Pemetrexed. A dose limiting toxicity (DLT) event is defined as any of the following events: 1. CTCAE Grade 4 event (ANC<1000/ul, body temperature≥38.5°C); 2. Grade 3 non-hematologic toxicity (except for nausea and vomiting that could be improved with optimal supportive care, escalation of alkaline phosphatase) If a DLT is experienced in any cohort, the cohort will be expanded to 6 subjects. If 2 DLTs are experienced in any cohort, the dose escalation ceased. The MTD was defined as the dose having at most two out of six patients experience DLT. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Be≥18 years of age on the day of signing informed consent.
- Patients with histologic or cytologic confirmation of advanced or metastatic NSCLC with stage III or IV disease amenable to platinum-based chemotherapy were assessed for eligibility.
- Patients with EGFR、ALK、ROS1 Mutation-negative were eligible.
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status.
- Life expectancy ≥3 months.
Key exclusion criteria (22 listed)
- Small cell lung cancer (include Small cell lung cancer mixture of NSCLC).
- Patients with brain or central nervous system metastases, including leptomeningeal disease, or CT/MRI examination revealed brain or leptomeningeal disease） (14 days before the random treatment has been completed and the symptoms of patients with brain metastases from stable can into the group, but need to the cerebral MRI, CT or vein angiography confirmed as without symptoms of cerebral hemorrhage).
- Iconography (CT or MRI) shows that the tumor vessels have 5 mm or less, or Cardiovascular involvement by Central tumor ; Or obvious lung empty or necrotic tumor.
- Uncontrollable hypertensive (systolic blood pressure or greater 140 mmHg or diastolic blood pressure or greater 90 mmHg, despite the best drug treatment).
- Significant cardiac disease as defined as: grade II or greater myocardial infarction, unstable arrhythmia(Including corrected QT interval (QTc )period between male or greater 450 ms, female or greater 470 ms); New York Heart Association (NYHA) grade II or greater heart dysfunction , or Echocardiography reveal left ventricular ejection fraction （LVEF）Less than 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 |
|---|---|---|
| AnlotinibAnlotinib 8mg p.o. qd in first cohort (3 subjects). 10mg p.o. qd in second cohort (3 subjects). 12mg p.o. qd in third cohort (3 subjects). | Drug | Anlotinib Plus Docetaxel, Anlotinib Plus Pemetrexed |
| PemetrexedPemetrexed 500mg/m2 as a 10-minute intravenous infusion on day 1 of a 21-day cycle. | Drug | Anlotinib Plus Pemetrexed |
| DocetaxelAlso: TaxotereDocetaxel 60mg/m2 as a 10-minute intravenous infusion on day 1 of a 21-day cycle. | Drug | Anlotinib Plus Docetaxel |
Primary outcome
Dose limiting toxicity
Time frame: From enrollment to completion of study. Estimated about 6 months.
Dose Limiting Toxicity (DLT) is referred to grade 3 non-hematological toxicity or grade 4 hematological toxicity according to NCI CTCAE 4.03 criteria
Maximum tolerance dose
Time frame: From enrollment to completion of study. Estimated about 6 months
Maximum Tolerance Dose (MTD) is the dose of treatment in the cohort where there are 2 cases of DTL reported.
2 secondary outcomes
disease control rate
Time frame: From enrollment to 2 months after treatment
time to progression
Time frame: From enrollment to progression of disease. Estimated about 6 months.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2018.
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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.
Lin Gen principal investigator
Fujian Cancer Hospital
Questions about this trial
What is this clinical trial studying?
A study testing Anlotinib, Pemetrexed and Docetaxel in people with Non-squamous Non-small Cell Lung Cancer, run by Fujian Cancer Hospital.
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 12 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: status not confirmed, as of the sponsor's last update on 25 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
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.
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 Lin Gen (13313786157, lingen197505@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting toxicity (time frame: From enrollment to completion of study. Estimated about 6 months.). The study lists 2 primary outcomes in all. 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 25 Jun 2018.