2023-509761-21-00招募中3 期
CARE : Impact of Regorafenib in combination with multimodal metronomic chemotherapy (cyclophosphamide, capecitabine, and low-dose aspirin) on progression-free survival compared with standard Regorafenib for the treatment of chemo-resistant metastatic colorectal cancers
Centre Hospitalier Regional Universitaire10 个研究点 分布在 1 个国家目标入组 174 人开始时间: 2024年3月25日最近更新:
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 174
- 试验地点
- 10
- 主要终点
- Progression-free survival (PFS): defined as the time from the randomization date to disease progression as per RECIST v1.1 or death from any cause, whichever occurs first. Alive patients without progression will be censored at last radiological evaluation available in the study arms treatment setting showing no progression.
研究概览
简要总结
The main objective is to evaluate the impact of a Regorafenib combined with metronomic chemotherapy (capecitabine and cyclophosphamide) and low-dose aspirin compared to standard Regorafenib treatment in patients with metastatic colorectal cancer by assessing progression-free survival.)
研究设计
- 分配方式
- Randomized
- 主要目的
- Période De Traitement
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically proven metastatic colorectal cancer in progression after previous standard treatments (5FU, CPT11, oxaliplatin, anti-VEGF, trifluridine/tipiracil, and anti-EGFR therapy if KRAS and NRAS WT, anti-BRAF therapy if BRAF V600E mutated, and anti-PD1 if MSI-H/dMMR tumor), or not considered as candidate for these treatments.
- •No contraindication to Iodine contrast media injection during CT
- •For female patients of childbearing potential, negative pregnancy test within 14 days before starting the study drug. Men and women are required to use adequate birth control during the study (when applicable),
- •Signed and dated informed consent,
- •Ability to comply with the study protocol, in the Investigator’s judgment.
- •Registration in a national health care system (CMU included).
- •Life expectancy of at least 3 months
- •Female or male with age >18 years old
- •Performance status = 0 or 1 (Annex 1)
- •Measurable disease defined according to RECIST v1.1 guidelines (scanner or MRI) (Annex 2)
- •Adequate bone marrow, liver and renal functions: Haemoglobin ≥ 9 g/dL; absolute neutrophil count (ANC) ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L, Total serum bilirubin ≤ 1.5 times upper normal value (ULN), serum alkaline phosphatase < 5 times ULN, aminotransferases (AST/ALT) ≤ 3 × ULN in absence of hepatic metastasis or ≤ 5 if presence of hepatic lesions, Cockcroft glomerular filtration rate > 50 ml/min, Proteinuria <2+ (dipstick urinalysis) or ≤1g/24hour
排除标准
- •Diagnosis of additional malignancy within 2 years prior to the inclusion (exception of curatively treated basal cell carcinoma of the skin and/or curatively resected in situ cervical and/or bladder cancer),
- •Known hypersensitivity to any of the study drugs, study drug classes or excipient in the formulation: - History of severe and unexpected reactions to fluoropyrimidine therapy, - History of asthma induced by the administration of salicylates or substances with a similar action, notably non-steroidal anti-inflammatory medicines, - Mastocytosis, for whom the use of acetylsalicylic acid can cause severe hypersensitivity reactions,
- •Unresolved toxicity higher than CTCAE (v5) Grade 1 attributed to any prior therapy/procedure excluding alopecia, hypothyroidism and oxaliplatin induced neuropathy ≤ Grade 2,
- •Subject unable to swallow oral medications or any malabsorption condition,
- •Inadequate organ functions: - known cardiac failure of unstable coronaropathy, respiratory failure, or uncontrolled infection or another life-risk condition - Congestive Heart Failure ≥ New York Heart Association (NYHA) class 2, - Myocardal infarction less than 6 months before start of study drug, unstable angina (anginal symptoms at rest), new-onset angina (begun within the last 3 months), Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted), - Uncontrolled hypertension (defined by systolic blood pressure ≥ 150 mmHg and/or diastolic pressure ≥ 100 mmHg despite optimal medical management), or history of hypertensive crisis, or hypertensive encephalopathy - Pleural effusion or ascites that causes respiratory compromise (≥ CTCAE grade 2 dyspnea), - Interstitial lung disease with ongoing signs or symptoms, - Ongoing infection >grade 2 CTCAE V5, - Dehydration CTCAE v5 grade ≥1, - Urinary tract obstruction
- •Constitutional or acquired hemorrhagic disease: - Any haemorrhage or bleeding event ≥ CTCAE Grade 3 within 4 weeks prior to the start of study medication, - History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to inclusion, - Serious, Non-healing wound, active peptic ulcer or untreated bone fracture, - Major surgical procedure, open biopsy or significant traumatic injury within 28 days before start of study medication,
- •Planned surgical procedure within the first month of treatment or any procedure that might change the timing of regorafenib administration during the first month of treatment,
- •Known History of human immunodeficiency virus (HIV) infection; Active hepatitis B or C or chronic hepatitis B or C requiring treatment with antiviral therapy,
- •Receipt of yellow fever vaccine within 28 days prior to study,
- •History of organ allograft,
- •Pregnant or breast-feeding subjects
- •Current participation in a study of an investigational agent or in the period of exclusion
- •Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before inclusion in the trial ;
- •Patient under judicial protection (curatorship, tutorship) and/or deprived of freedom,
- •Previous exposition to regorafenib or anti-angiogenic treatment other than bevacizumab and aflibercept
- •Treatment with any other investigational medicinal product within 28 days prior to study entry, EXCEPT for ASPIRIN,
- •Systemic anticancer therapy including cytotoxic therapy, signal transduction inhibitors, immunotherapy, and hormonal therapy during this trial or within 3 weeks,
- •Chronic treatment with drug potentially interacting with regorafenib i.e. CYP3A4, CYP2C9 or UGT1A9 inductor/inhibitor; Epilectic disorder requiring medication; Recent or concomitant treatment with brivudine,
- •Complete deficit in dihydropyrimidine deshydrogenase (DPD),
结局指标
主要结局
Progression-free survival (PFS): defined as the time from the randomization date to disease progression as per RECIST v1.1 or death from any cause, whichever occurs first. Alive patients without progression will be censored at last radiological evaluation available in the study arms treatment setting showing no progression.
Progression-free survival (PFS): defined as the time from the randomization date to disease progression as per RECIST v1.1 or death from any cause, whichever occurs first. Alive patients without progression will be censored at last radiological evaluation available in the study arms treatment setting showing no progression.
次要结局
- Health related Quality of life : - EORTC QLC30 + CR29, EQ-5D-5L questionnaires - 5 prespecified targeted dimensions of interest : Global health/ Pain/ Physical Functioning / Fatigue / Emotional Functioning - Number of days of hospitalization
- Toxicities graded according to NCI-CTCAE criteria version
- Overall survival (OS): defined as the time from the randomization date to death from any cause. Alive patients will be censored at the last date known to be alive, either during study treatment period or during follow-up period.
- Disease control rate (DCR): DCR is defined as the proportion of participants with best overall response of confirmed CR or PR or stable disease (SD).
- Duration of objective response (DOR): defined as the time from the first documented objective response of PR or CR, whichever is noted earlier, to disease progression or death (if death occurs before progression is documented). DOR will be defined for responders only, i.e. patients with a CR or PR. The actual dates the tumor scans were performed will be used for this calculation. DOR for patients who have not progressed or died at the time of analysis will be censored at the date of last TM
- Evaluation of CHUN morphological criteria
- Economic evaluation: incremental cost-utility ratio: EuroQol-5D-5L (EQ-5D-5L) questionnaire and VAS (repeated measures at baseline, W8, M4, M6, M8, M10, M12 and end of study M18)
研究者
Magali REBUCCI-PEIXOTO
Scientific
Centre Hospitalier Regional Universitaire
研究点 (10)
Loading locations...
相似试验
招募中
3 期
Trial assessing a regorafenib-irinotecan combination (REGIRI) versus regorafenib alone in metastatic colorectal cancer patients after failure of standard therapies.2024-512555-21-00Institut Regional Du Cancer De Montpellier78
招募中
1 期
Phase Ib study of the combination of regorafenib with conventional chemotherapy for the treatment of newly diagnosed patients with multimetastatic Ewing sarcoma - REGO-INTER-EWING12023-503322-39-00Institut Gustave Roussy26
招募中
3 期
RegoNivo vs Standard of Care Chemotherapy in AGOC (INTEGRATEIIb)2023-505441-69-00Institut fuer Klinische Krebsforschung IKF GmbH125
招募中
1 期
CApivasertib, Venetoclax And Low-intensity chemotheRapY for Adults With ALL/LBLLymphomaLeukemiaNCT07294677University of Chicago104
尚未招募
2 期
A Phase 2 Randomized, Controlled Trial of QL1706 Plus Chemotherapy and Quad Shot for Driver Gene-negative Advanced Non-small Cell Lung Cancer.NCT07271602Union Hospital, Tongji Medical College, Huazhong University of Science and Technology104