Metronomic Chemotherapy With Anti-angiogenic Effect as Maintenance Treatment for Metastatic Colorectal Carcinoma Following Response to FOLFIRI+Bevacizumab: Clinical and Laboratory Studies
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Length of progression free survival (PFS), measured in months.
研究概览
简要总结
Colorectal cancer patients with metastases (mCRC) at response under expensive chemotherapy which may be toxic +/- exhausting are candidates for an effective and more convenient maintenance treatment.
Objectives:
- To define the efficacy of maintenance chemotherapy by a low-dose metronomic (LDM) regimen, in metastatic CRC patients responding under FOLFIRI + bevacizumab.
- To discover predictive factors for response to this LDM regimen.
Hypothesis:
- The re-growth of residual metastases can be slowed by the anti-angiogenic effects of LDM chemotherapy.
- Serial measurements of angiogenic/ inflammatory factors in the plasma and/or evaluation of certain enzymes in the tumor may discover predictive factors of response to LDM chemotherapy in metastatic CRC patients.
详细描述
At entry to the research protocol the up-till then administered treatment with Intra Venous FOLFIRI+BEVACIZUMAB will be stopped.Instead, the research oral treatment will be initiated to be taken daily on an ambulatory basis and under once monthly re-evaluation. If and when disease progresses the original FOLFIRI+BEVACIZUMAB treatment will be considered for re-institution.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologic (or cytologic) proof of colorectal carcinoma (CRC).
- •Age: between 18 and
- •Sex: both sexes.
- •Previous treatment for metastatic disease is limited to FOLFIRI+ bevacizumab.
- •Prior adjuvant chemotherapy, with a fluoropyrimidine and/or Oxaliplatin, is allowed.
- •Prior radiotherapy, either as adjuvant treatment or palliation of metastatic sites is allowed, provided that there are other non-irradiated foci of disease for evaluation.
- •Persistent remission, either complete, partial or minimal response (CR, PR or MR) or stable disease (SD), one year+/-one month from initiation of first line treatment for mCRC.
- •Asymptomatic patients at break from chemotherapy.
- •Intact organ function, including complete blood counts (CBC) showing normal values or any toxicity limited to grade 1 and blood chemistry (SMA) showing liver and renal functions < 1.5 upper normal limit (UNL).
- •Capability to understand and to sign the informed consent.
排除标准
- •Concurrent any other cancer (except BCC or squamous cell carcinoma of skin).
- •Inability to adhere to monthly visits to the oncology unit for evaluation.
- •Presence of brain metastases.
- •Any current or recent (within the last month) continuous treatment by steroids or by NSAIDs, or with therapeutic doses of anticoagulants for any reason.
- •Previous radiotherapy to the only site of measurable disease.
- •Evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac including arrhythmias, hepatic or renal disease), and/or existence of active peptic ulcer (clinically and/or by gastroscopy).
研究组 & 干预措施
LDM anti-angiogenic chemotherapy
LDM (Low Dose Metronomic) anti-angiogenic chemotherapy includes daily oral treatment with CAPECITABINE, CELECOXIB and METHOTREXATE.
干预措施: CAPECITABINE, CELECOXIB and METHOTREXATE (Drug)
结局指标
主要结局
Length of progression free survival (PFS), measured in months.
时间窗: Up to 12 months.
From start of the experimental treatment until the date of first documented progression or date of death of any cause,whichever came first, assessed up to 12 months.
次要结局
- Quality of life, as expressed by FACT-C.(Up to 12 months.)
- Toxicity profile of treatment, defined by CTCAE Version 4.0.(up to12 months)
- Changes in levels of angiogenic factors while under treatment: VEGF, PDGF, TSP-1(Up to 4 months.)