- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT04029350
Study of Anlotinib Combined With Osimertinib as Second-line Treatment in Stage IIIb-IV NSCLC With Confirmed EGFRm and T790M (ALTN-03)
2019년 8월 19일 업데이트: 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.
연구 개요
상세 설명
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.
연구 유형
중재적
등록 (예상)
53
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Hebei
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Shijiazhuang, Hebei, 중국
- Fourth Hospital of Hebei Medical University
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Shijiazhuang, Hebei, 중국
- Hebei Provincial People's Hospital
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Shanxi
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Taiyuan, Shanxi, 중국
- Shanxi Provincal Cancer Hospital
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Tianjin
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Tianjin, Tianjin, 중국, 300060
- Tianjin Medical University Cancer Institute and Hospital
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
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
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: 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.
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Progression-free survival (PFS)
기간: 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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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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DCR(질병관리율)
기간: 독성 또는 PD에 대한 내약성까지 각 42일(최대 24개월)
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2주기마다 강화된 CT/MRI 스캔을 통해 안로티닙 염산 캡슐 플러스 이코티닙 염산 정제의 효과를 평가합니다.
질병 통제율(DCR)은 질병 통제 최고 전체 반응(완전 반응, 부분 반응 또는 안정 질병)을 보이는 참가자의 비율로 정의됩니다.
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독성 또는 PD에 대한 내약성까지 각 42일(최대 24개월)
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부작용
기간: 30일 안전 추적 방문까지
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안전성 및 내약성의 척도로서 부작용이 있는 참가자 수
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30일 안전 추적 방문까지
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ORR(객관적 응답률)
기간: 독성 또는 PD에 대한 내약성까지 각 42일(최대 24개월)
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2주기마다 강화된 CT/MRI 스캔을 통해 안로티닙 염산 캡슐 플러스 이코티닙 염산 정제의 효과를 평가합니다.
객관적 반응률(ORR)은 완전 반응(CR) 또는 부분 반응(PR)을 보인 참가자를 총 환자 수로 나눈 값으로 정의됩니다.
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독성 또는 PD에 대한 내약성까지 각 42일(최대 24개월)
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OS(Overall Survival)
기간: 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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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
수사관
- 수석 연구원: Richeng Jiang, Doctor, Tianjin Medical University Cancer Institute and Hospital
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
일반 간행물
- 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.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2019년 7월 31일
기본 완료 (예상)
2020년 1월 31일
연구 완료 (예상)
2021년 11월 30일
연구 등록 날짜
최초 제출
2019년 7월 21일
QC 기준을 충족하는 최초 제출
2019년 7월 21일
처음 게시됨 (실제)
2019년 7월 23일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2019년 8월 21일
QC 기준을 충족하는 마지막 업데이트 제출
2019년 8월 19일
마지막으로 확인됨
2019년 6월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- ALTN-03-II-01
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
예
IPD 계획 설명
De-identified individul participant data for all primary and secondary outcome measures will be made available.
IPD 공유 기간
Data will be available within 6 months of study completion
IPD 공유 액세스 기준
Data access requests will be reviewed by an external indepentent Review Panel.
Requestors will be required to sign a Data Access Agreement.
IPD 공유 지원 정보 유형
- 연구_프로토콜
- 수액
- ICF
- ANALYTIC_CODE
- CSR
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
아니
미국 FDA 규제 기기 제품 연구
아니
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
비소세포폐암에 대한 임상 시험
-
Millennium Pharmaceuticals, Inc.완전한GCB(Non-Germinal B-cell-like) 미만성 거대 B-세포 림프종(DLBCL)미국