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- Register voor klinische proeven in de VS.
- Klinische proef NCT04029350
Study of Anlotinib Combined With Osimertinib as Second-line Treatment in Stage IIIb-IV NSCLC With Confirmed EGFRm and T790M (ALTN-03)
19 augustus 2019 bijgewerkt door: Tianjin Medical University Cancer Institute and Hospital
A Multi-center, One-arm, Phase II Trial of Anlotinib Combined With Osimertinib as the Second-line Treatment in Stage IIIb-IV NSCLC With Confirmed EGFRm and T790M.
Evaluate the efficacy and safety of Anlotinib combined with Icotinib as the second-line treatment in stage IIIb-IV NSCLC patients with sensitive EGFR and T790M mutations.
Studie Overzicht
Toestand
Onbekend
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
Anlotinib Hydrochloride is a kind of innovative medicines approved by State Food and Drug Administration(CFDA:2011L00661) which was developed by Jiangsu Chia-tai Tianqing Pharmaceutical Co., Ltd.
Anlotinib is a kinase inhibitor of receptor tyrosine with multi-targets, especially for VEGFR1、VEGFR2、VEGFR3、FGFR1/2/3、PDGFRa/β and c-Kit.
Studietype
Ingrijpend
Inschrijving (Verwacht)
53
Fase
- Fase 2
Contacten en locaties
In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.
Studie Locaties
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Hebei
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Shijiazhuang, Hebei, China
- Fourth Hospital of Hebei Medical University
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Shijiazhuang, Hebei, China
- Hebei Provincial People's Hospital
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Shanxi
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Taiyuan, Shanxi, China
- Shanxi Provincal Cancer Hospital
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Tianjin
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Tianjin, Tianjin, China, 300060
- Tianjin Medical University Cancer Institute and Hospital
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Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
18 jaar tot 75 jaar (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
Inclusion Criteria:
- Histologically or cytologically confirmed, locally advanced and/or metastatic IIIB, IIIC or IV non-squamous NSCLC or recurrent non-squamous NSCLC (according to the 8th Edition of the AJCC Staging system).
- Non-small cell lung cancer (NSCLC) with an activating EGFR mutation (exon 19 deletion, L858R point mutation, or any other mutation known to be associated with EGFR TKI sensitivity); presence of an activating EGFR mutation may be documented in tumor tissue or by plasma testing.
- Locally confirmed T790M mutation determined from biopsy (preferred) or on circulating tumour DNA, documented in tissue, plasma or serum after disease progression on the most recent first- or second-generation EGFR TK treatment regimen.
- 18-75years,ECOG PS:0-2,Life expectancy of more than 3 months,with measurable lesion ( RECIST1.1).
- ≥1 target lesion that has not received radiotherapy in the past 3 months and can be accurately measured in at least 1 direction;Previously received radiation therapy, but the radiotherapy area must be <25% of the bone marrow area, and radiation therapy must have closed for at least≥4 weeks at the time of enrollment.
- Main organs function is normal.
- Signed and dated informed consent.
- The woman patients of childbearing age must agree to take contraceptive methods during the research and within another 8 weeks after treatment. Pregnancy test (blood serum test or urine) should be done within 7 days before the research and the result should be negative.The man patients who must agree to take contraceptive methods during the research and within another 8 weeks after treatment.
Exclusion Criteria:
- Squamous cell carcinoma (including adenosquamous carcinoma); Small Cell Lung Cancer (including small cell cancer and other kinds of cancer mixed with non-small cell cancer)
- Non-small cell lung cancer (NSCLC) with an EGFR C797S mutation.
- Prior treatment with a third-generation EGFR TKI (i.e. Rociletinib, Olmutinib、BPI-15086、BPI-7711、Osimertinib); Prior treatment with agents targeting the VEGF pathway, including bevacizumab and Anlotinib.
- Treatment with an EGFR TKI (i.e. erlotinib, gefitinib or afatinib) within 8 days or approximately 5 x half-life, whichever is longer, of the first dose of study treatment;Patients may not be receiving any other investigational agents and may not have participated in a study of an investigational agent or using an investigational device within five half-lives of the compound or 3 months, whichever is greater
- Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia and grade 2 platinum-therapy related neuropathy
- Any factor that would preclude adequate absorption of Osimertinib and Anlotinib, including refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection
- Patients with obvious brain metastases, cancerous meningitis, spinal cord compression, or with brain or pia mater disease. (patient with brain metastases who have completed treatment 28 days before and the symptoms are stable can be Enrolled, also should have no cerebral hemorrhage symptoms confirmed by brain MRI, CT or venography evaluation
- Patients who planned to receive systemic anti-tumor therapy within 4 weeks prior to allocation or during the course of this study, including cytotoxic therapy, signal transduction inhibitors, immunotherapy (or receiving the Mitomycin C 6 weeks prior to medication). Extra-field radiotherapy (EF-RT) was performed 4 weeks prior to allocation or restricted radiotherapy for assessing tumor lesions within 2 weeks prior to allocation
Patients with any severe and/or uncontrolled disease, including:
- Inadequately controlled hypertension (HTN) (systolic blood pressure [SBP] > 140 mmHg and/or diastolic blood pressure [DBP] > 90 mmHg despite antihypertensive medication)
- Mean resting corrected QT interval (Fridericia's correction formula [QTcF]) > 470 ms ms obtained from 3 electrocardiograms (ECGs), using the screening clinic ECG machine derived corrected QT (QTc) value; Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block); Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval;
- Active or uncontrollable serious infection (≥CTC AE Level 2 infection)
- Liver cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis need to be treated with antiretroviral therapy
- Poor control of diabetes (fasting blood glucose [FBG]> 10 mmol/L)
- Urine routine test protein ≥++, and confirmed 24 hours urine protein> 1.0 g
- Long-term unhealed wounds or fractures
- Evidence of bleeding diathesis or coagulopathy (including clinically significant hemoptysis)
- Patients with artery/venous thrombotic occurred within 12 months before allocation, such as cerebrovascular accident (including temporary ischemic attack), deep vein thrombosis and pulmonary embolism
- Past medical history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease
- Patients with a history of psychotropic medicine abuse and cannot quit or have mental disorders
- Respiratory syndrome (dyspnea≥CTC AE 2), severe pleural effusion, ascites, pericardial effusion
- History of immunodeficiency, including HIV-positive or other acquired, congenital immunodeficiency disease, or history of organ transplantation; active infection including hepatitis B (HBV DNA level ≥1000 copies /mL), hepatitis C and human immunodeficiency virus (HIV)
- Has a history of malignant tumors. Except for patients with cutaneous basal cell carcinoma, superficial bladder cancer, cutaneous squamous cell carcinoma or orthotopic cervical cancer who have undergone curative treatment and have no disease recurrence within 5 years after the start of treatment
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD9291 (osimertinib) or Anlotinib
- Patient was diagnosed with disease which will severely endanger the security of patients or influence the completion of this research; Judgment by the investigator that should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
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Experimenteel: Anlotinib Combined With Osimertinib
Anlotinib 12 mg once a day from day 1 to 14 of a 21-day cycle.
Osimertinib 80mg p.o, qd.
It should be continued until disease progress or toxicity cannot be tolerated or patients withdraw consent.
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Anlotinib:12mg/capsule, take once when limosis in the morning. If patients suffer from AEs, they can get declined dosage (10mg or 8mg). Osimertinib:80 mg/tablet, per os (p.o.) daily. It should be continued until disease progression or intolerable toxicity or patients withdraw of consent.
Andere namen:
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Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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Progression-free survival (PFS)
Tijdsspanne: each 42 days up to PD or death (up to 24 months)
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The PFS time is defined as time from enrollment to locoregional or systemic recurrence, second malignancy or death due to any cause; censored observations will be the last date of : "death", "last tumor assessment", "last follow up date" or "last date in drug log"
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each 42 days up to PD or death (up to 24 months)
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Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
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DCR (ziektebestrijdingspercentage)
Tijdsspanne: elke 42 dagen tot intolerantie de toxiciteit of PD (tot 24 maanden)
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Om de effectiviteit van Anlotinib Hydrochloric Capsule Plus Icotinib Hydrochloric Tablet te evalueren door elke twee cycli een verbeterde CT/MRI-scan te maken.
Disease Control Rate (DCR) gedefinieerd als het percentage deelnemers met de beste algehele respons van Disease Control (volledige respons, gedeeltelijke respons of stabiele ziekte).
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elke 42 dagen tot intolerantie de toxiciteit of PD (tot 24 maanden)
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Bijwerkingen
Tijdsspanne: Tot 30 dagen veiligheidsopvolgbezoek
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Aantal deelnemers met bijwerkingen als maatstaf voor veiligheid en verdraagbaarheid
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Tot 30 dagen veiligheidsopvolgbezoek
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ORR (objectief responspercentage)
Tijdsspanne: elke 42 dagen tot intolerantie de toxiciteit of PD (tot 24 maanden)
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Om de effectiviteit van Anlotinib Hydrochloric Capsule Plus Icotinib Hydrochloric Tablet te evalueren door elke twee cycli een verbeterde CT/MRI-scan te maken.
Objective Response Rate (ORR) wordt gedefinieerd als deelnemers met volledige respons (CR) of gedeeltelijke respons (PR) gedeeld door het totale aantal patiënten.
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elke 42 dagen tot intolerantie de toxiciteit of PD (tot 24 maanden)
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OS(Overall Survival)
Tijdsspanne: up to 24 months
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OS was defined as time from date of enrollment to date of death due to any cause.
For participants still alive at the time of analysis, OS time was censored on last date that participants were known to be alive.
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up to 24 months
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Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Medewerkers
Onderzoekers
- Hoofdonderzoeker: Richeng Jiang, Doctor, Tianjin Medical University Cancer Institute and Hospital
Publicaties en nuttige links
De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.
Algemene publicaties
- Han B, Li K, Wang Q, Zhang L, Shi J, Wang Z, Cheng Y, He J, Shi Y, Zhao Y, Yu H, Zhao Y, Chen W, Luo Y, Wu L, Wang X, Pirker R, Nan K, Jin F, Dong J, Li B, Sun Y. Effect of Anlotinib as a Third-Line or Further Treatment on Overall Survival of Patients With Advanced Non-Small Cell Lung Cancer: The ALTER 0303 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2018 Nov 1;4(11):1569-1575. doi: 10.1001/jamaoncol.2018.3039. Erratum In: JAMA Oncol. 2018 Nov 1;4(11):1625.
- Mok TS, Wu Y-L, Ahn M-J, Garassino MC, Kim HR, Ramalingam SS, Shepherd FA, He Y, Akamatsu H, Theelen WS, Lee CK, Sebastian M, Templeton A, Mann H, Marotti M, Ghiorghiu S, Papadimitrakopoulou VA; AURA3 Investigators. Osimertinib or Platinum-Pemetrexed in EGFR T790M-Positive Lung Cancer. N Engl J Med. 2017 Feb 16;376(7):629-640. doi: 10.1056/NEJMoa1612674. Epub 2016 Dec 6.
- Akamatsu H, Teraoka S, Morita S, Katakami N, Tachihara M, Daga H, Yamamoto N, Nakagawa K. Phase I/II Study of Osimertinib With Bevacizumab in EGFR-mutated, T790M-positive Patients With Progressed EGFR-TKIs: West Japan Oncology Group 8715L (WJOG8715L). Clin Lung Cancer. 2019 Jul;20(4):e492-e494. doi: 10.1016/j.cllc.2019.03.002. Epub 2019 Mar 19.
- Seto T, Kato T, Nishio M, Goto K, Atagi S, Hosomi Y, Yamamoto N, Hida T, Maemondo M, Nakagawa K, Nagase S, Okamoto I, Yamanaka T, Tajima K, Harada R, Fukuoka M, Yamamoto N. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study. Lancet Oncol. 2014 Oct;15(11):1236-44. doi: 10.1016/S1470-2045(14)70381-X. Epub 2014 Aug 27. Erratum In: Lancet Oncol. 2014 Oct;15(11):e475.
- Saito H, Fukuhara T, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, Yoshimori K, Nakachi I, Gemma A, Azuma K, Kurimoto F, Tsubata Y, Fujita Y, Nagashima H, Asai G, Watanabe S, Miyazaki M, Hagiwara K, Nukiwa T, Morita S, Kobayashi K, Maemondo M. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung cancer (NEJ026): interim analysis of an open-label, randomised, multicentre, phase 3 trial. Lancet Oncol. 2019 May;20(5):625-635. doi: 10.1016/S1470-2045(19)30035-X. Epub 2019 Apr 8.
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start (Werkelijk)
31 juli 2019
Primaire voltooiing (Verwacht)
31 januari 2020
Studie voltooiing (Verwacht)
30 november 2021
Studieregistratiedata
Eerst ingediend
21 juli 2019
Eerst ingediend dat voldeed aan de QC-criteria
21 juli 2019
Eerst geplaatst (Werkelijk)
23 juli 2019
Updates van studierecords
Laatste update geplaatst (Werkelijk)
21 augustus 2019
Laatste update ingediend die voldeed aan QC-criteria
19 augustus 2019
Laatst geverifieerd
1 juni 2019
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Ziekten van de luchtwegen
- Neoplasmata
- Longziekten
- Neoplasmata per site
- Neoplasmata van de luchtwegen
- Thoracale neoplasmata
- Carcinoom, bronchogeen
- Bronchiale neoplasmata
- Longneoplasmata
- Carcinoom, niet-kleincellige long
- Moleculaire mechanismen van farmacologische werking
- Enzymremmers
- Antineoplastische middelen
- Proteïnekinaseremmers
- Osimertinib
Andere studie-ID-nummers
- ALTN-03-II-01
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
JA
Beschrijving IPD-plan
De-identified individul participant data for all primary and secondary outcome measures will be made available.
IPD-tijdsbestek voor delen
Data will be available within 6 months of study completion
IPD-toegangscriteria voor delen
Data access requests will be reviewed by an external indepentent Review Panel.
Requestors will be required to sign a Data Access Agreement.
IPD delen Ondersteunend informatietype
- LEERPROTOCOOL
- SAP
- ICF
- ANALYTIC_CODE
- MVO
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Nee
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Nee
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .
Klinische onderzoeken op Niet-kleincellige longkanker
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National Cancer Centre, SingaporeBeëindigdExtranodaal NK-T-CELL LYMFOMASingapore
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Adelphi Values LLCBlueprint Medicines CorporationVoltooidMastcelleukemie (MCL) | Agressieve systemische mastocytose (ASM) | SM w Assoc Clonal Hema Non-Mast Cell Lineage Disease (SM-AHNMD) | Smeulende systemische mastocytose (SSM) | Indolente systemische mastocytose (ISM) ISM-subgroep volledig gerekruteerdVerenigde Staten
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University of Alabama at BirminghamBeëindigdAnaplastisch grootcellig lymfoom | Angioimmunoblastisch T-cellymfoom | Perifere T-cellymfomen | Volwassen T-celleukemie | Volwassen T-cellymfoom | Perifeer T-cellymfoom niet gespecificeerd | T/Null Cell Systemisch Type | Cutaan t-cellymfoom met nodale / viscerale ziekteVerenigde Staten
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Masonic Cancer Center, University of MinnesotaWervingLymfoom | Folliculair lymfoom | Acute myeloïde leukemie | Multipel myeloom | Myelofibrose | Juveniele myelomonocytaire leukemie | Burkitt lymfoom | Acute lymfatische leukemie | Lymfoblastisch lymfoom | Chronische lymfatische leukemie | Lymfoplasmacytisch lymfoom | Acute leukemie | Mantelcellymfoom | Chronische myelogene... en andere voorwaardenVerenigde Staten
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Roswell Park Cancer InstituteActief, niet wervendAcute myeloïde leukemie | Polycytemie Vera | Myelofibrose | Chronische myelomonocytische leukemie | Waldenström Macroglobulinemie | Acute lymfatische leukemie | Chronische lymfatische leukemie | Secundaire acute myeloïde leukemie | Sikkelcelziekte | Myelodysplastisch syndroom | Plasmacelmyeloom | Chronische... en andere voorwaardenVerenigde Staten
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Masonic Cancer Center, University of MinnesotaBeëindigdFolliculair lymfoom | Myelodysplastische syndromen | Multipel myeloom | Hodgkin lymfoom | Burkitt lymfoom | Acute lymfatische leukemie | Chronische lymfatische leukemie | Lymfoplasmacytisch lymfoom | Acute myeloïde leukemie | Mantelcellymfoom | Chronische myelogene leukemie | Prolymfatische Leukemie | Klein lymfocytisch... en andere voorwaardenVerenigde Staten
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Masonic Cancer Center, University of MinnesotaActief, niet wervendFolliculair lymfoom | Acute myeloïde leukemie | Multipel myeloom | Hodgkin lymfoom | Lymfoplasmacytisch lymfoom | Acute leukemie | Myelodysplastisch syndroom | Chronische myelogene leukemie | Prolymfatische Leukemie | Plasmacelleukemie | Beenmergfalensyndromen | Burkitt-lymfoom | Acute lymfoblastische leukemie... en andere voorwaardenVerenigde Staten
Klinische onderzoeken op Anlotinib Combined With Osimertinib
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Shanghai Chest HospitalWervingUitgezaaide kanker | Adenocarcinoom van de longen | Niet-kleincellige longkanker met EGFR-mutatie | Lokaal geavanceerde vaste tumorChina