Non-squamous Non-small Cell Lung CancerNCT03602027
Phase I Study of the Combination of Anlotinib With Gefitinib
A study testing Anlotinib and Gefitinib in people with Non-squamous Non-small Cell Lung Cancer, run by Second Affiliated Hospital of Nanchang University.
Trial summary
The purpose of this clinical study is to evaluate the tolerability and toxicity of different dose of Anlotinib puls Gefitinib in First-line Treatment of Advanced Gene Positive 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 75 years
- Conditions the study is for
- Non-squamous Non-small Cell Lung Cancer
- What is being tested?
- Anlotinib and Gefitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- No sites listed yet
- Study dates
- 1 Aug 2018to 1 Feb 2019
- 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 75 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 and With good compliance and agree to accept follow-up of disease progression and adverse events.
- Patients with histologic or cytologic confirmation of advanced or metastatic NSCLC with stage III or IV disease.（For recurrent patients, adjuvant chemotherapy, neoadjuvant chemotherapy or neoadjuvant chemotherapy plus adjuvant were assessed for eligibility, and the last treatment time must be more than 6 months before enrollment）
- Epidermal Growth Factor Receptor(EGFR)mutations confirmed by molecular detection (including, but not limited to, 20 exon, 19 exon deletion and L858R) external pathological examination was accepted (including pathological or blood test results)
- Patients have not been received systematic treatment，including chemotherapy and EGFR -TKIs（Tyrosine kinase inhibitors）
- There were at least one target lesions in the past three months has not yet accepted radiotherapy, and could be recorded by magnetic resonance imaging (MRI) or computer tomography (CT) measuring accurately at least in one direction(The maximum diameter needs to be recorded), including conventional CT ≥20 mm or spiral CT ≥10 mm.
- Life expectancy ≥3 months.
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- Have a performance status of 0 or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Status.
- With normal marrow, liver ,renal and coagulation function:
- The blood routine examination need to be standard (no blood transfusion and blood products within 14 days, no g-csf and other hematopoietic stimulating factor correction)
- Hemoglobin（HB）≥90 g/L
- A Neutrophil count of （ANC）≥1.5×109/L
- A Platelet count of （PLT）≥80×109/L
- A Total bilirubin (TBil) of ≤1.5 upper normal limitation (UNL)
- A alanine aminotransferase (ALAT) and a aspartate aminotransferase (ASAT) of ≤2.5 UNL, in case of liver metastasis ALAT and ASAT≤5 UNL
- A creatinine (Cr) of ≤1.5 UNL; a creatinine clearance rate ≥ 60ml/min (Cockcroft-Gault)
- Doppler echocardiography: left ventricular ejection fraction (LVEF) is lower than normal (50%)
- 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.
Who cannot join
- Small cell lung cancer (include Small cell lung cancer mixture of NSCLC).
- 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.
- Patients has a history of malignant tumors. Patients with basal cell carcinoma, superficial bladder cancer, skin squamous cell carcinoma, or cervical cancer in situ who have undergone possible curative treatment and have not suffered any recurrence of the disease within 5 years from the start of treatment.
- Patients with Other active malignant tumors requiring concurrent treatment
- Patients who have not recovered to grade 1 or below after previous systemic antitumor therapy (except alopecia)
- 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)
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- 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%
- Patients with grade II or greater peripheral neuropathy, except due to trauma
- Abnormal coagulation (INR > 1.5 or prothrombin time (PT) >Upper Limit of Normal( ULN)+ 4 seconds or APTT（activated partial thromboplastin time ） ULN > 1.5, with bleeding tendency or be treated with thrombolysis and anticoagulation.
- 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 respiratory syndrome (difficulty breathing of level 2 or higher ), serous cavity effusion need to surgical treatment ( including pleural of level 2 or higher with respiratory distress and anoxia, need for intubation or pleurodesis treatment, severe ascites of level 2 need to surgery invasive treatment, pericardial of level 2 and affect physiological function)
- Patients with severe infections , and need to receive systemic antibiotic treatment.（ the infection with grade 2 or above and requiring intravenous antibacterial therapy ）;Decompensated diabetes or other contraindication with high dose glucocorticoid therapy）
- Active or chronic hepatitis c and/or Hepatitis B virus (HBV) infection
- Serious, non-healing wound, ulcer, or bone fracture
- 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
- Patients have participated in other antitumor drug clinical trials Within 4 weeks before enrollment or prepare to receive systemic anti-tumor treatment during the study or Within 4 weeks before randomization, including cytotoxic therapy cellular, Signal transduction inhibitors, immune therapy (or receiving mitomycin C Within six weeks before taking experimental drug therapy).Field overspread radiotherapy (ef-rt) was carried out within 4 weeks before the grouping or limited field radiotherapy was carried out within 2 weeks before the grouping to evaluate tumor lesions
- 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.
- Patients who have a history of mental drug abuse and cannot be cured or have mental disorders
- There are any contraindications with receiving anlotinib or gefitinib treatment
- There are allergic reaction to contrast media, anlotinib, and/or excipient of experimental drug
- There are allergic reaction to the contrast agent
- 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 Gefitinib in the First-line Treatment of Advanced Gene Positive 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 Gefitinib in First-line Treatment of Advanced Gene Positive 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 Gefitinib in patients of Advanced GenePositive 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 were instructed to take Gefitinib 250mg orally daily for three weeks and 8mg/10mg/12mg Anlotinib orally daily on day 1 to 14 of a 21-day cycle.
- Conditions
- Non-squamous Non-small Cell Lung Cancer
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 low-dose groups (3 subjects). 10mg p.o. qd in middle-dose groups (3 subjects). 12mg p.o. qd in high-dose groups (3 subjects).
GefitinibDrug
Gefitinib 250mg orally daily for three weeks
| Study group | Role | What they receive |
|---|---|---|
| Anlotinib Plus Gefitinib | Experimental | This study will include a sequential evaluation of 3 subjects per dose group. low-dose groups: Anlotinib 8mg per day and Gefitinib. middle-dose groups: Anlotinib 10mg per day and Gefitinib. high-dose groups: Anlotinib 12mg per day and Gefitinib.
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 dose group, the cohort will be expanded to 6 subjects. If 2 DLTs are experienced in any dose group, 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: Gefitinib |
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 4 months.
Maximum tolerance dose
Maximum Tolerance Dose (MTD) is the dose of treatment in the cohort where there are 2 cases of DLT reported.
Measured: From enrollment to completion of study. Estimated about 4 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 posted26 Jul 2018
- Study start1 Aug 2018 (estimated)
- Primary completion1 Dec 2018 (estimated)
- Study completion1 Feb 2019 (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 Second Affiliated Hospital of Nanchang 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03602027
- Sponsor's protocol ID
- ALTERL007
- Status last verified
- Jul 2018
- First submitted
- 18 Jul 2018
- Last updated
- 26 Jul 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose Climbing Trial of Anlotinib Plus Gefitinib in the First-line Treatment of Advanced Gene Positive Non-squamous Non-small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT03602027
- Acronym / sponsor ID
- ALTERL007
- Conditions
- Non-squamous Non-small Cell Lung Cancer
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 9 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital of Nanchang UniversityUniversity, hospital or other
- Study start
- 1 Aug 2018 (estimated)
- Primary completion
- 1 Dec 2018 (estimated)
- Study completion
- 1 Feb 2019 (estimated)
- First posted
- 26 Jul 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 Gefitinib in First-line Treatment of Advanced Gene Positive 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 Gefitinib in patients of Advanced GenePositive 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 were instructed to take Gefitinib 250mg orally daily for three weeks and 8mg/10mg/12mg Anlotinib orally daily on day 1 to 14 of a 21-day cycle.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anlotinib Plus Gefitinib | Experimental | Drug: Anlotinib, Drug: GefitinibThis study will include a sequential evaluation of 3 subjects per dose group. low-dose groups: Anlotinib 8mg per day and Gefitinib. middle-dose groups: Anlotinib 10mg per day and Gefitinib. high-dose groups: Anlotinib 12mg per day and Gefitinib. 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 dose group, the cohort will be expanded to 6 subjects. If 2 DLTs are experienced in any dose group, 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 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Be≥18 years of age on the day of signing informed consent and With good compliance and agree to accept follow-up of disease progression and adverse events.
- Patients with histologic or cytologic confirmation of advanced or metastatic NSCLC with stage III or IV disease.（For recurrent patients, adjuvant chemotherapy, neoadjuvant chemotherapy or neoadjuvant chemotherapy plus adjuvant were assessed for eligibility, and the last treatment time must be more than 6 months before enrollment）
- Epidermal Growth Factor Receptor(EGFR)mutations confirmed by molecular detection (including, but not limited to, 20 exon, 19 exon deletion and L858R) external pathological examination was accepted (including pathological or blood test results)
- Patients have not been received systematic treatment，including chemotherapy and EGFR -TKIs（Tyrosine kinase inhibitors）
- There were at least one target lesions in the past three months has not yet accepted radiotherapy, and could be recorded by magnetic resonance imaging (MRI) or computer tomography (CT) measuring accurately at least in one direction(The maximum diameter needs to be recorded), including conventional CT ≥20 mm or spiral CT ≥10 mm.
Key exclusion criteria (27 listed)
- Small cell lung cancer (include Small cell lung cancer mixture of NSCLC).
- 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.
- Patients has a history of malignant tumors. Patients with basal cell carcinoma, superficial bladder cancer, skin squamous cell carcinoma, or cervical cancer in situ who have undergone possible curative treatment and have not suffered any recurrence of the disease within 5 years from the start of treatment.
- Patients with Other active malignant tumors requiring concurrent treatment
- Patients who have not recovered to grade 1 or below after previous systemic antitumor therapy (except alopecia)
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 low-dose groups (3 subjects). 10mg p.o. qd in middle-dose groups (3 subjects). 12mg p.o. qd in high-dose groups (3 subjects). | Drug | Anlotinib Plus Gefitinib |
| GefitinibGefitinib 250mg orally daily for three weeks | Drug | Anlotinib Plus Gefitinib |
Primary outcome
Dose limiting toxicity
Time frame: From enrollment to completion of study. Estimated about 4 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 4 months
Maximum Tolerance Dose (MTD) is the dose of treatment in the cohort where there are 2 cases of DLT 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 26 Jul 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.
Questions about this trial
What is this clinical trial studying?
A study testing Anlotinib and Gefitinib in people with Non-squamous Non-small Cell Lung Cancer, run by Second Affiliated Hospital of Nanchang University.
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 17 inclusion and 27 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 26 Jul 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 Liu An wen (13767120022, awliu666@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 4 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 26 Jul 2018.