2024-515788-73-00招募中2 期
FFCD - 1703 - POCHI : PEMBROLIZUMAB in combination with XELOX or FOLFOX-BEVACIZUMAB in patients with Microsatellite Stable (MSS) metastatic colorectal cancer and a high immune infiltrate: a proof-of-concept study. Phase II – non-randomised- multicentre.
Fondation Franc.Cancerologie Digestive86 个研究点 分布在 1 个国家目标入组 55 人开始时间: 2024年7月30日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 55
- 试验地点
- 86
- 主要终点
- The primary endpoint is the percentage of patients alive and without progression at 10 months. Progression is defined by: - radiological progression evaluated by the investigator according to RECIST v1.1 criteria. - death, whatever the cause
研究概览
简要总结
To evaluate the efficacy of pembrolizumab in combination with XELOX or FOLFOX and bevacizumab as 1st line treatment of microsatellite stable (MSS) metastatic colorectal cancer (mCRC) with a high immune infiltrate. Efficacy will be determined by analysis of the number of patients alive and without radiological and/or clinical progression at 10 months (based on RECIST 1.1 criteria evaluated by the investigator).
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Adequate liver function: AST/ALT ≤ 5xULN, total bilirubin ≤ 2xULN, Alkaline phosphatase ≤ 5xULN
- •Creatinine clearance > 50 mL/min according to the CKD-EPI formula
- •Proteinuria <2+ (dipstick urinalysis) or ≤1g/24hour
- •Patient who is a beneficiary of the social security system
- •Information provided to patient and signature of the informed consent form
- •Both MSS and pMMR metastatic colorectal adenocarcinoma (metachronous or synchronous metastases), histologically proven
- •Patients who have had adjuvant/post-operative chemotherapy and/or post-operative radiotherapy for the treatment of their primary tumor or R0 resected metastatic lesions can be included if they have a recurrence more than 6 months after the end of this treatment
- •High immune response defined as the immune infiltration score obtained on the primary tumour (resection of primary tumour containing at least 2 mm of tumour-free margin between the tumour and nontumour area)
- •Unresectable cancer with at least one measurable metastatic target according to RECIST v1.1 criteria
- •Absence severe neuropathy (≥ grade 2) (chemo-induced or not)
- •Life expectancy > 3 months
- •Adequate haematological function: neutrophils > 1,500 /mm3, platelets > 100,000/mm3, Hb > 9 g/dL
排除标准
- •Active infection requiring intravenous antibiotics at day 1 of cycle 1
- •Another concomitant cancer or history of cancer during the last 5 years, except for carcinoma in situ of the uterine cervix or a basal cell or squamous cell skin carcinoma or any other carcinoma in situ considered as cured
- •Previous bone marrow allogenic stem cell transplantation or previous organ transplantation
- •Previous treatment with anti-PD1 or anti-PDL1 or another immunotherapy
- •History of idiopathic pulmonary fibrosis, medicinal product-related pneumonia or proof of active pneumonia or pneumonitis on a chest CTscan prior to therapy
- •HIV infection, active hepatitis B or C infection, active tuberculosis
- •Colorectal cancer with microsatellite instability (dMMR and/or MSI)
- •Patient eligible for curative treatment (resection and/or thermal ablation according to the opinion of the local multidisciplinary tumour meeting board) and patient with RAS wild-type tumour for whom a tumour shrinkage with an anti-EGFR is necessary to perhaps obtain a XML File Identifier: IjpoCuOJiXEw1TRpi8rHlb0n7yE= Page 27/63 downstaging for a secondary surgery (according to the opinion of the local multidisciplinary tumour meeting board and/or at investigator's discretion)
- •Patient with only primary tumour biopsies available or only a sample of a metastasis (no surgical resection of the primary tumour)
- •An auto-immune disease which may worsen during treatment with an immune-stimulating agent (patients with type I diabetes, vitiligo, psoriasis, hypo or hyperthyroidism not requiring immunosuppressant therapy are eligible)
- •Long-term immunosuppressant therapy (patients requiring corticosteroid therapy are eligible if administration at a dose ≤ 10 mg prednisone equivalent dose per day, administration of steroids by a route of administration resulting in minimal systemic exposure (cutaneous, rectal, ocular or inhalation) is authorised)
- •All uncontrolled progressive disorders during the last 6 months: hepatic insufficiency, renal insufficiency, respiratory insufficiency, arterial hypertension
- •Known severe hypersensitivity to monoclonal antibodies, to one of the medicinal products used or to one of the excipients in the products used or a history of anaphylactic shock or of uncontrolled asthma
- •Vaccinations (live vaccine) within 30 days prior to start of treatment
- •Dihydropyrimidine Dehydrogenase (DPD) deficiency defined by uracilemy level ≥ 16 ng/mL
- •QT/QTc interval > 450 msec in men and > 470 msec in women
- •One of the following disorders during the 6 months prior to inclusion: myocardial infarction, unstable/severe angina pectoris, coronary artery bypass grafting, NYHA class II, III or IV congestive heart failure, stroke or transient ischaemic attack
- •Concomitant treatment with brivudine or brivudine within 4 weeks before capecitabine or 5FU initiation
- •Poor nutritional status
- •History of an inflammatory digestive disease, obstruction or subobstruction not resolved with symptomatic treatment
- •Active or untreated central nervous system metastases
- •Peptic ulcer disease not healed before the treatment
- •Patient already enrolled in another therapeutic trial with an ongoing investigational drug or whose treatment ended less than 4 weeks before inclusion
- •Absence of effective contraception in patients (male and/or female patients) of childbearing potential, a pregnant or breastfeeding woman, women of childbearing potential and who have not had a pregnancy test
- •Impossibility to submit to medical follow-up of the trial due to geographic, social or psychological reasons
- •Patients who have had neo-adjuvant treatment (chemotherapy or radiotherapy) for the treatment of primary tumor can not be included
结局指标
主要结局
The primary endpoint is the percentage of patients alive and without progression at 10 months. Progression is defined by: - radiological progression evaluated by the investigator according to RECIST v1.1 criteria. - death, whatever the cause
The primary endpoint is the percentage of patients alive and without progression at 10 months. Progression is defined by: - radiological progression evaluated by the investigator according to RECIST v1.1 criteria. - death, whatever the cause
次要结局
- Overall survival: is defined as time between date of inclusion and date of death of patient (whatever the cause) or date of last news if patient is XML File Identifier: IjpoCuOJiXEw1TRpi8rHlb0n7yE= Page 28/63 alive
- Grades 3 – 4 adverse events: will be evaluated according to NCI-CTC v4.0 criteria and described by maximum grade based on total duration of treatment and 30 days after treatment
- Secondary resection rate (R0 and R1): is defined as the percentage of patients who underwent surgery on their metastatic lesions after the protocol treatment.
- Histological response in case of secondary resection: is evaluated according to the TRG (Rubbia-Brandt L et al. Annals Oncol 2007), in patients who underwent a secondary resection. This response is evaluated according to the various categories: TRG1/TRG 2/TRG 3/TRG 4/TRG 5.
- Outcome of tumour markers (CEA and CA19.9): the evolution of the markers will be analyzed by a graphic representation of the percentage change from baseline rate.
- Progression-free survival, according to the investigator (RECIST criteria): defined as time between date of inclusion and date of a first radiological progression or date of death (whatever the cause). Patients alive without progression will be censured at date of last news. According to iRECIST criteria, progression will be considered as an event if it is confirmed. If the patient dies before confirmation, the event will be considered as unconfirmed progression.
- The percentage of patients alive and without progression at 10 months (according to centralised review, RECIST and iRECIST criteria): progression is defined as radiological progression or death, whatever the cause. According to iRECIST criteria, the patient will be considered as in progression if progression is confirmed in the next 2 months.
- Time to progression, according to the investigator (RECIST criteria) and in centralised review (RECIST and iRECIST criteria): is defined as the time between date of inclusion and date of first progression (RECIST v1.1 criteria) or date of suspected progression if confirmed (iRECIST criteria).
- Time to an objective response (according to the investigator and in centralised review, RECIST criteria): is defined as the time between the date of inclusion and the date of a first objective response (complete response or partial response) during treatment. Patients with no imaging study (or if best response is not evaluable, or patients not treated) will not be taken into account in the analysis.
- Best response during treatment (according to the investigator and in centralised review, RECIST criteria): the best response is described by a percentage according to different categories: complete response (CR), partial response (PR), stability (S), progression (P) and not evaluable (NE). The best objective response is evaluated during treatment based on different imaging studies and according to RECIST v1.1 criteria.
- Depth of response (according to the investigator and in centralised review, RECIST criteria): is defined as the relative difference between the sum total of the largest diameters of target lesions in NADIR (RECIST v1.1: in the absence of new lesions or progression of non-target lesions) and the sum total of the largest diameters of target lesions at inclusion.
- Early tumour shrinkage at 9 weeks, according to the investigator (RECIST criteria) and in centralised review (RECIST and iRECIST criteria): is defined as the relative difference between the sum of the largest diameters of the target lesions at 9 weeks and the sum of different targets at inclusion. Tumour shrinkage corresponds to a relative difference > 20% with RECIST v1.1 criteria and > 30% with iRECIST.
研究者
David TOUGERON
Scientific
Fondation Franc.Cancerologie Digestive
研究点 (86)
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