Trifluridine/Tipiracil (TAS-102) With or Without Thalidomide for the Treatment of Metastatic Colorectal Cancer
TACTIC: a Phase II Study of TAS-102 Monotherapy and Thalidomide Plus TAS-102 as Third-line Therapy and Beyond in Patients With Advanced Colorectal Carcinoma
연구 개요
상세 설명
In the past decade, the use of targeted drugs has greatly improved the overall survival of patients with mCRC. However, there are currently few effective drugs available clinically. Trifluridine/Tipiracil (TAS-102) is a novel cytotoxic antitumor drug taken orally with minor adverse reactions, consisting of trifluridine and tipyrimidine hydrochloride. Tas-102 has been approved for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy; an anti-VEGF biological therapy; and if RAS wild type, an anti-EGFR therapy. Multiple studies have shown that TAS-102 prolongs median OS and PFS in mCRC patients compared with placebo.
Thalidomide is a sedative that was developed in the late 1950s and eventually marketed and prescribed in several countries to pregnant women to alleviate nausea in the late 1950s and early 1960s. The drug, however, caused severe birth defects in more than 10,000 children worldwide and was forced to withdraw from the international market. Further studies found that the S-optical isomer of thalidomide can inhibit neutrophil chemotaxis, produce anti-inflammatory activity, stimulate immune system activation, regulate immunity, anti-angiogenesis, and inhibit the adhesion of cancer cells to stroma, so as to change the microenvironment of the body, and achieve anti-tumor effect.
Thalidomide has both anti-angiogenesis and antiemetic effects, and its combined use with TAS-102 may reduce the gastrointestinal reactions associated with TAS-102, while enhancing antitumor efficacy and reducing the side effects of chemotherapy, and its cost is significantly lower than that of bevacizumab, which has higher pharmacoeconomics and greater clinical research application value.
연구 유형
등록 (예상)
단계
- 2 단계
연락처 및 위치
연구 연락처
- 이름: Zengqing Guo
- 전화번호: +86 13860603879
- 이메일: gzq_005@126.com
연구 장소
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Fuzhou, 중국
- 아직 모집하지 않음
- First Affiliated Hospital of Fujian Medical University
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연락하다:
- Rixiong Rixiong Wang
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Fuzhou, 중국
- 아직 모집하지 않음
- Fujian Provincial People's Hospital
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연락하다:
- Wujin Chen
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Fuzhou, 중국
- 아직 모집하지 않음
- Fuzhou First Hospital affiliated to Fujian Medical University
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연락하다:
- Jingrong Liu
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Fuzhou, 중국
- 아직 모집하지 않음
- Hospital 900 of the Joint Logistic Support Force of the Chinese People's Liberation Army
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연락하다:
- Fangwei Xie
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Fuzhou, 중국
- 아직 모집하지 않음
- The Third People's Hospital affiliated to Fujian University of Chinese Medicine
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연락하다:
- Wenwu Wang
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Fujian
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Fuzhou, Fujian, 중국
- 모병
- Fujian Medical University Cancer Hospital, Fujian Cancer Hospital
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연락하다:
- Zengqing Zengqing Guo
- 전화번호: +86 13860603879
- 이메일: gzq_005@126.com
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
- Have histological or cytological documentation of adenocarcinoma of the colon or rectum (mCRC).
- For patients with disease progression after conventional treatment, TAS-102 is determined as the third-line therapy or beyond according to the routine treatment practice of the researcher.
- Aged no less than 20 years.
5.Have a measurable disease, according to RECIST version 1.1 6.Eastern Cooperative Oncology Group performance status 0-2. 7.Life expectancy of at least 12 weeks. 8.For women with reproductive potential, serum tests were performed within 7 days before the start of study treatment β- Human chorionic gonadotropin (β- HCG) pregnancy test, the result is negative. Women with reproductive potential must agree to take appropriate contraceptive measures with informed consent until at least 6 months after the last use of the study drug.
9.Sufficient bone marrow, liver and kidney functions and meet the following laboratory requirements:
- Platelet count ≥75 × 109 /L
- Hemoglobin level ≥90 g/L
- Absolute neutrophil count ≥1.5× 109 /L
a) Total bilirubin ≤1.5 × upper limit of normal (ULN) b) Alanine aminotransferase and aspartate aminotransferase ≤2.5 × ULN (≤5 × ULN for patients with liver metastases) d) Serum creatinine ≤1.5 × ULN e) Glomerular filtration rate ≥30 ml/min/1.73 m2, according to the modified diet in renal disease abbreviated formula 10.Able to take oral drugs. 11.Have signed written informed consent.
Exclusion criteria
- With arterial or venous thrombosis or embolic events such as myocardial infarction, cerebral thrombosis, intracerebral hemorrhage, deep venous thrombosis or pulmonary embolism within 6 months before the start of the study.
- Evidence or history of any bleeding diathesis, irrespective of severity. Any hemorrhage or bleeding event ≥ grade 3 (adverse events per CTCAE v5.0) within 4 weeks prior to the start of treatment.
- Peripheral neuropathy > grade 1 (adverse events per CTCAE v5.0).
- History of uncontrolled or medicated heart disease.
- Seizure disorder requiring medication.
- Known history of human immunodeficiency virus (HIV) infection.
- Patients with an active infection.
- Other uncontrolled concurrent diseases determined by the researchers as not meeting the study conditions.
- Patients with ascites and pleural effusion with clinical symptoms requiring treatment.
- Known allergy to any of the study drug ingredients.
- Unable to swallow oral medication.
- Prior exposure to TAS-102 or thalidomide.
- Patients who have brain metastases.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: TAS-102+Thalidomide
Thalidomide 100mg PO BID+TAS-102 35mg/m2, po, bid, d1-5, d8-12, q4wks
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For the experimental group, the intervention was thalidomide（100mg PO Bid)
다른 이름들:
TAS-102
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활성 비교기: TAS-102
TAS-102 35mg/m2, po, bid, d1-5, d8-12, q4wks
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TAS-102
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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무진행생존기간(PFS)
기간: 무작위 배정 날짜부터 처음 문서화된 진행 날짜 또는 모든 원인으로 인한 사망 날짜 중 먼저 도래한 날짜까지 최대 100개월 평가
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무진행생존(PFS)은 무작위 배정부터 조사관이 평가한 방사선학적 질병 진행 또는 어떤 원인으로 인한 사망이 처음 발생한 날짜 중 먼저 도래한 날짜까지의 시간으로 정의되었습니다.
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무작위 배정 날짜부터 처음 문서화된 진행 날짜 또는 모든 원인으로 인한 사망 날짜 중 먼저 도래한 날짜까지 최대 100개월 평가
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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전반적인 생존(OS)
기간: 무작위 배정 날짜부터 모든 원인으로 인한 사망 날짜 중 먼저 도래하는 날짜까지 최대 100개월 평가
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OS는 임의의 원인으로 인한 무작위 배정 날짜부터 사망 날짜까지의 시간으로 정의되었습니다.
생존했거나 데이터 분석 마감일까지 후속 조치를 취하지 못한 피험자의 경우 생존은 피험자의 마지막 알려진 생존 시간에서 중도절단되었습니다.
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무작위 배정 날짜부터 모든 원인으로 인한 사망 날짜 중 먼저 도래하는 날짜까지 최대 100개월 평가
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치료-응급 부작용의 발생률
기간: 첫 투여부터 마지막 투여 후 30일 이내
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치료 관련 부작용 발생률은 NCI CTC AE 버전 5.0에 따라 평가되었습니다.
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첫 투여부터 마지막 투여 후 30일 이내
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공동 작업자 및 조사자
간행물 및 유용한 링크
일반 간행물
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- Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D, Aranda Aguilar E, Bardelli A, Benson A, Bodoky G, Ciardiello F, D'Hoore A, Diaz-Rubio E, Douillard JY, Ducreux M, Falcone A, Grothey A, Gruenberger T, Haustermans K, Heinemann V, Hoff P, Kohne CH, Labianca R, Laurent-Puig P, Ma B, Maughan T, Muro K, Normanno N, Osterlund P, Oyen WJ, Papamichael D, Pentheroudakis G, Pfeiffer P, Price TJ, Punt C, Ricke J, Roth A, Salazar R, Scheithauer W, Schmoll HJ, Tabernero J, Taieb J, Tejpar S, Wasan H, Yoshino T, Zaanan A, Arnold D. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016 Aug;27(8):1386-422. doi: 10.1093/annonc/mdw235. Epub 2016 Jul 5.
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추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- TACTIC
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
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