- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03706287
Efficacy and Safety of Anlotinib Plus Platinum Plus Pemetrexed in T790M-negative NSCLC
Efficacy and Safety of Anlotinib Combined With Platinum Plus Pemetrexed in T790M Mutation Negative Metastastic Non-squamous Non-small-cell Lung Cancer After Progression on First-line EGFR TKI: a Phase II, Muti-center, Single Arm Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Anlotinib, an oral highly potent tyrosine-kinase inhibitor targeting VEGFR、PDGFR、FGFR and c-kit,has demonstrated improved survival in previously treated patients with advanced non-small-cell lung cancer(NSCLC).
In the phase Ⅲ study ALTER0303, 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. Therefore,we envisage using anlotinib plus platinum plus pemetrexed treat the EGFR wild-type metastatic non-small cell lung cancer patients who were failure in the treatment of chemotherapy with platinum containing drugs, to further improve the patient's PFS.
The study is divided into two stages,phase I use a dose escalation trial design to explore the safety, tolerability, dose-limiting toxicities(DLT), Maximum Tolerable Dose(MTD), A cohort of 3~6 subjects will be enrolled at each dose level, If 0 of 3 or ≤ 1 of 6 subjects experience a DLT, the phase I trial will move ahead to the next dose until ≥ 2 of 6 subjects experience a DLT,and the current dose will be considered the MTD. Following completion of the dose escalation trial and determination of MTD(Phase I), a single arm study including 44 subjects may be enrolled to further evaluate safety, tolerability, and efficacy of anlotinib in combination with platinum plus pemetrexed in the same target population(phase II). Phase II is to designed to explore the anti-tumor activity of anlotinib combined with platinum plus pemetrexed in T790M mutation negative metastatic non-squamous non-small cell lung cancer(NSCLC) after the failure of EGFR-TKI.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: juan li
- Phone Number: +86 13880276636
- Email: dr.lijuan@hotmail.com
Study Locations
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-
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Chengdu, China
- Not yet recruiting
- Chengdu Fifth People's Hospital
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Contact:
- mei mei
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Principal Investigator:
- mei mei
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Deyang, China
- Not yet recruiting
- People's Hospital of Deyang City
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Contact:
- zhaohong chen
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Luzhou, China
- Not yet recruiting
- The Affiliated Hospital of Southwest Medical University
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Contact:
- sheng lin
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Principal Investigator:
- Sheng Lin
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Nanchong, China
- Not yet recruiting
- Nanchong Central Hospital
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Principal Investigator:
- xin hu
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Suining, China
- Not yet recruiting
- Suining Central Hospital
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Contact:
- qiang zhou
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Principal Investigator:
- qiang zhou
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Sichuan
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Chengdu, Sichuan, China, 610041
- Recruiting
- Sichuan Cancer Hospital
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Principal Investigator:
- ping yu, doctor
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- ≥ 18 and ≤ 75 years of age. Signed the informed consent form prior to patient entry
- Histologically or pathologically confirmed non-squamous non-small cell lung cancer(NSCLC) with stage IV .
- Epidermal Growth Factor Receptor(EGFR)mutations confirmed by molecular detection (including, but not limited to 19 exon deletion and L858R) external pathological examination was accepted (including pathological or blood test results)
- Patients have only be treated with EGFR -TKIs(Tyrosine kinase inhibitors)including gefitinib, elotinib or icotinib, and received a best response of PR for ≥4months or SD for 6 months; disease has progressed recently according to RECIST 1.1 and negative for T790M detection(detection methods including ddPCR、ARMS or NGS) (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)
- Must have at least one measurable lesion as per RECIST 1.1 defined as a lesion that is 10mm in longest diameter imaged by CT scan or MRI;prior topical treatment, such as radiotherapy cryosurgery to the lesions is not allowed in less than 3 months;
- Life expectancy ≥3 months.
- Eastern Cooperative Oncology Group(ECOG) performance status 0 or 1.
- Toxicity caused by prior anti-cancer treatments was restored to ≤ level 1 in CTC AE (4.0) , except alopecia;
- 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 (ALT) and a aspartate aminotransferase (AST) 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)
- The woman patients of childbearing age who must agree to take contraceptive methods during the research and within another 8 weeks after it and examined as negative in blood serum test or urine pregnancy test within 7 days before the research; the man patients who must agree to take contraceptive methods during the research and within another 8 weeks;
- Voluntarily joined the study and signed informed consent, with good compliance and follow-up.
Exclusion Criteria:
- Small Cell Lung Cancer mixed or squamous mixed;
- No squamous NSCLC with hemoptysis (>50ml/day);
- Symptomatic brain metastases after treatment;
- Tumor locate within a distance of less than 5 mm from the large vessels, less than 2 cm from the bronchial tree, or has invaded local large vessels; tumor with cavum or necrotic obviously;
- Uncontrolled hypertension (systolic ≥150mmHg and/or diastolic ≥100mmHg, despite optimal drug therapy).
- Patients with with grade Ⅱ myocardial ischemia or myocardial infarction, poor control of arrhythmias (including QTc interval male ≥ 450 ms, female ≥470 ms); according to NYHA standard, grade Ⅲ ~ Ⅳ heart failure, or cardiac color Doppler ultrasound examination showed left ventricular ejection fraction (LVEF) <50%.
- Coagulation dysfunction (INR> 1.5, PT> ULN +4s or APTT> 1.5 ULN), with bleeding tendency or ongoing thrombolysis or anti-blood coagulation treatment;note: 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
- Patients whose routine urine tests indicate that urine protein ≥ ++ or verifies that the 24-h urine protein quantitation ≥ 1.0 g.
- Patients whose has peripheral neuropathy over level 2 in CTC AE4.0, except trauma.
- 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
- Patients who have unhealed wounds or fractures for a long time.
- Patients with severe infections , and need to receive systemic antibiotic treatment
- Decompensated diabetes or other contraindication with high dose glucocorticoid therapy;
- Cirrhosis or decompensated liver disease; active or untreated hepatitis C and/or Hepatitis B virus (HBV) infection(prior hepatitis B history, HBsAg positive and HBV DNA≥500IU/mL; HCV RNA positive and hepatic Insufficiency
- History of immunodeficiency, HIV infection etc
- Active pulmonary tuberculosis;
- Has an obvious factor influencing oral drug absorption, such as unable to swallow, chronic diarrhea and intestinal obstruction, etc
- Patients who received major surgical operations or experienced severe traumatic injuries, bone fracture, or ulcers within 4 weeks before screening.
- Severe weight loss (> 10%) Within 6 weeks before Random
- Patients who had obvious hemoptysis (>50ml/day) within 3 months before screening; Patients who experienced bleeding symptoms of clinical significance within 3 months before screening, or with confirmed bleeding tendency such as hemorrhage of digestive tract, hemorrhagic gastric ulcer, baseline occult blood in stool ++ and above, or vasculitis, etc;
- Patients who manifested arterial/venous thrombus events, e.g. cerebrovascular accident (including transient ischemic attack), deep venous thrombosis and pulmonary embolism, etc., within 12 months before screening.
- Allergic reactions to anotol or excipients in experimental drugs.
- Allergic reactions to contrast medium
- 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
- Patients with any other medical condition or reason, in that investigator's opinion, makes the patient unstable to participate in a clinical trial.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Anlotinib + AP/PC
|
anlotinib 8mg/d, q.d., p.o. 1-14days every 21 days Pemetrexed(A) 500mg/m2, IV, Day 1; Cisplatin(P) 25mg/m2,IV,Day 1-3 or Carboplatin(C) area under curve(AUC)=5, IV, Day 1; AP or AC will be administered every 21 days starting on Day 1.
Other Names:
anlotinib 10mg/d, q.d., p.o. 1-14days every 21 days Pemetrexed(A) 500mg/m2, IV, Day 1; Cisplatin(P) 25mg/m2,IV,Day 1-3 or Carboplatin(C) area under curve(AUC)=5, IV, Day 1; AP or AC will be administered every 21 days starting on Day 1.
Other Names:
anlotinib 12mg/d, q.d., p.o. 1-14days every 21 days Pemetrexed(A) 500mg/m2, IV, Day 1; Cisplatin(P) 25mg/m2,IV,Day 1-3 or Carboplatin(C) area under curve(AUC)=5, IV, Day 1; AP or AC will be administered every 21 days starting on Day 1.
Other Names:
anlotinib doses to be determined following the completion of Phase I of the study, q.d., p.o. 1-14days every 21 days Pemetrexed(A) 500mg/m2, IV, Day 1; Cisplatin(P) 25mg/m2,IV,Day 1-3 or Carboplatin(C) area under curve(AUC)=5, IV, Day 1; AP or AC will be administered every 21 days starting on Day 1.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free survival (PFS)
Time Frame: 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.
|
Up to 24 months
|
Dose limiting toxicity (DLT)
Time Frame: 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
|
Estimated about 6 months
|
Maximum tolerance dose (MTD)
Time Frame: Estimated about 6 months
|
Maximum Tolerance Dose (MTD) is the dose of treatment in the cohort where there are 2 cases of DLT reported.
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Estimated about 6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety (Number of Participants with Adverse Events as a Measure of Safety and Tolerability)
Time Frame: Until 21 day safety follow-up visit
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Number of Participants with Adverse Events as a Measure of Safety and Tolerability
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Until 21 day safety follow-up visit
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Objective response rate(ORR)
Time Frame: Up to 24months
|
To determine ORR of Anlotinib Anlotinib combined with Platinum-based Pemetrexed in T790M mutation negative Advanced NSCLC.
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.
|
Up to 24months
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Disease Control Rate (DCR)
Time Frame: Up to 24months
|
Defined as the proportion of patients with a documented complete response, partial response, and stable disease (CR + PR + SD) based on RECIST 1.1.
|
Up to 24months
|
Duration of Response (DOR)
Time Frame: Up to 24months
|
Defined as the the time from first confirmed CR or PR until the first date of either objective disease progression or death due to any cause.
|
Up to 24months
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: ping yu, Sichuan Cancer Hospital and Research Institute
- Principal Investigator: juan li, doctor, Sichuan Cancer Hospital and Research Institute
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Lung Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Nucleic Acid Synthesis Inhibitors
- Enzyme Inhibitors
- Antineoplastic Agents
- Folic Acid Antagonists
- Carboplatin
- Cisplatin
- Pemetrexed
Other Study ID Numbers
- ALTER-L022
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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