Phase I Clinical Trial Testing the Dose Escalation and Expansion of Pressurized IntraThoracic Hyperthermic Aerosol Cisplatin Administration for the Management of Pleural Carcinosis
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 39
- 试验地点
- 1
- 主要终点
- Expansion phase (Part B):
研究概览
简要总结
Within the context of pleural carcinosis, the present study is a dose escalation with determination of the maximum tolerated doses (MTD) of pressurized cisplatin administration associated to moderate hyperthermia in the pleura. This will be followed by an expansion phase at the recommended dose (RD).
详细描述
Adverse events: the evaluation of the safety of cisplatin administered by PITHAC is the primary endpoint of both parts of the study Cisplatin administration will be performed on D0. Postoperative pain management according to the Enhanced Recovery After Surgery program following the surgical procedure.
Dyspnoea score will be scored at screening, and every day until D10 and checked one last time at D30 using the CR-10 scale.
Chest X-ray will be performed at screening, D0, 24h post intervention, D10 and D30.
Monitoring of adverse events (AEs), serious and non-serious, will be conducted throughout the study from the surgery.
Blood samples for cisplatin pharmacokinetics PK will be performed on D0 pre-intervention, 12h post intervention, 24h and 48h post intervention.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At least 18 years of age
- •Body weight at least 30 kg
- •Eastern cooperative oncology group performance status score of 0-2 at enrolment
- •Patient with pleural carcinosis that qualify for a surgical intervention for pleurodesis or placement of an indwelling permanent catheter.
- •Life expectancy of at least 3 months
- •Pathology-confirmed pleural carcinosis with malignant pleural effusion (either histological confirmation is already available based on a previous tru-cut pleural biopsy or previous pleural fluid cytology is positive for malignant cells or high suspicion of pleural carcinosis based on computed tomography imaging which must be confirmed by fresh frozen section analyses of tissue harvested during pithac operative procedure)
- •Non-small cell lung cancer, breast cancer, lymphoma, ovarian cancer, oesophageal cancer, gastric cancer, and malignant tumour of the serous membranes (mesothelioma) confirmed by pathology either as part of a diagnostic workup of suspected pleural carcinosis OR available from other previous examinations patients undergoing a planned videothoracoscopy to perform pleurodesis or a placement of a tunnelled catheter
- •Adequate liver, kidney, and bone marrow functions as assessed by laboratory tests (serum total bilirubin <1.5 mg/dl, aspartate transaminase and alanine transaminase less than 2.5 times the upper limit of the normal range, creatinine clearance ≥60 ml/min, absolute neutrophil count ≥1,500/μl, haemoglobin ≥90 g/L, platelets ≥100,000/μl)
- •I) Patients with past/resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible, if HBV DNA test is negative. Ii) HBV DNA must be obtained in patients with positive hepatitis B core antibody prior start of study treatment.
- •Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA
- •Adequate cardiac functions as assessed by echocardiography
- •Adequate birth control measures
- •Signed informed consent
排除标准
- •Patients with active or chronic hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at pre-screening)
- •Patients with active hepatitis C
- •Any known formal contra-indication for video-assisted thoracoscopy (VATS) according to pulmonary and cardiac preliminary investigations.
- •Systemic cytotoxic anticancer treatment within 10 days before and after enrolment except for inhibitors of vascular endothelial growth factor for which this period should be decided according to the used drug (for bevacizumab the period involves 4 weeks before and after enrolment, for lenvatinib 1 week before and 2 weeks after, and for sorafenib 1 week before and after), no limitations applied for immune checkpoint inhibitors
- •Major surgery within 28 days prior to enrolment
- •Any unresolved toxicity from previous anticancer therapy of grade ≥2 according to the CTCAE except for alopecia, vitiligo, and laboratory values considered as adequate in the inclusion criteria and any irreversible toxicity that is expected to have impact on the study results or be a contraindication for the planned surgical intervention or be worsened by the investigational procedure
- •Long lasting exposure to corticosteroids
- •Known allergy to platinum compounds
- •Non-small cell lung cancer with egfr or alk mutations unless refractory to tyrosine kinase inhibitor (thus off treatment)
- •Uncontrolled intercurrent illness
- •Clinically relevant hearing loss or tinnitus
- •Clinically relevant neuropathy
- •Life-threatening conditions (uncontrolled systemic infection etc.)
- •Previous administration (by any route) of a total cumulative dose of more than 500 mg/m2 of cisplatin
- •Secondary resistance to platinum compounds defined as tumour progression during platinum treatment or within 6 months after its cessation
- •pregnancy
- •judgement of the investigator that the patient is unlikely to comply with the study requirements
- •current enrolment in another prospective clinical trial
- •Incapacity of judgement
- •Patients in emergency situation
- •Myelossupression
- •Yellow fever vaccine
- •Concurrent prophylactic use of phenytoin
研究组 & 干预措施
Cohorte 1 _ 7.5 mg/m2
cohorte 1: 7.5 mg/m2 of cisplatin (once)
干预措施: Cisplatine Teva® (Drug)
Cohorte 2 _ 12.5 mg/m2
cohorte 2: 12.5 mg/m2 of cisplatin (once)
干预措施: Cisplatine Teva® (Drug)
cohorte 3: 35 mg/m2 of cisplatin
cohorte 3: 35 mg/m2 of cisplatin (once)
干预措施: Cisplatine Teva® (Drug)
cohorte 4: 70 mg/m2 of cisplatin
cohorte 4: 70 mg/m2 of cisplatin (once)
干预措施: Cisplatine Teva® (Drug)
结局指标
主要结局
Expansion phase (Part B):
时间窗: between 10 and 12 months
Safety profile of cisplatin administered by PITHAC will be assessed by the incidence of Adverse Events and Serious Adverse Events according to NCI-CTCAE criteria (v5). Incidence and severity of intraoperative and post-operative complications will be measured using the Clavien-Dindo classification up to 30 days after the intervention. Safety profile of cisplatin administered by PITHAC will be assessed by the incidence of Adverse Events and Serious Adverse Events according to NCI-CTCAE criteria (v5). Incidence and severity of intraoperative and post-operative complications will be measured using the Clavien-Dindo classification up to 30 days after the intervention.
Dose Escalation and Maximum Tolerated Dose determination (Part A):
时间窗: 18 months approximately
In order to determine the maximum tolerated dose (MTD) of cisplatin administered by PITHAC, the primary study outcome will be the occurrence of Dose Limiting Toxicities (DLT).
次要结局
- Dose Escalation and MTD determination (Part A):(18 months)
- Expansion phase (Part B):(10 /12 months)
研究者
Dr Jean Yannis PERENTES
Sponsor-Investigator
Centre Hospitalier Universitaire Vaudois