To Assess the Tolerance of Intraperitoneal (IP) Nivolumab After Extensive Debulking Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients With Advanced Ovarian Carcinoma, Through a Phase Ib/II Study Including Patients at 3 Dose-levels for Nivolumab
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Safety profile of the Intraperitoneal (IP) nivolumab treatment
研究概览
简要总结
Spread pattern, the lack of alternative treatments, and emerging data on the activity of anti-Programmed death ligand 1 (PDL1) targeted checkpoint inhibitor therapy in gynecological cancers provide the rationale for this investigation.
Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) are likely to increase the tumor-antigen expression and the mutational load. As a result, it would be interesting to combine this approach with immunotherapy. Moreover, Intraperitoneal (IP) infusion will directly target the peritoneal cavity and potentially enhance the immune response. Indeed some recent papers indicate that the peritoneum could be considered as a lymphoid organ, involving "milky spots", thus able to produce a better immune response when immunotherapy is given by IP route rather than intravenous (IV) route.
The investigating team in Lyon, France is one of the major groups for HIPEC research in Europe (Pr O. Glehen et al) - Reference center for the tumors of the peritoneum (French National Cancer Institute).
The aim of this study is to assess in this I/II phase study, the feasibility of extensive debulking surgery and HIPEC followed by Intraperitoneal (IP) nivolumab dose escalation in patients with advanced ovarian carcinoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients at least 18 years of age.
- •Signed informed consent and ability to comply with treatment and follow-up.
- •Histological or cytological proven primary epithelial ovarian carcinoma or peritoneal cancer or fallopian tube carcinoma in relapse, including serous papillary adenocarcinoma, mucinous adenocarcinoma, clear-cell carcinoma, undifferentiated carcinoma, mixed mullerian tumor and endometrioid adenocarcinoma. Patients with low grade tumors can be included.
- •Not eligible for front-line cytoreduction in first platinum-sensitive relapse
- •Eligible for surgical cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) after one or more lines of chemotherapy. All chemotherapy regimens usually recommended for the treatment of ovarian cancer are accepted :
- •Platinum based regimens +/- bevacizumab for the treatment of platinum sensitive disease.
- •Non - platinum based regimens +/- bevacizumab for the treatment of platinum resistant disease.
- •Satisfactory haematological evaluation: neutrophil rate greater than 1500/millimeters cubed, platelet count greater than 100 grams/liter;
- •Satisfactory renal and hepatic function: serum creatinine ≤1.5 times the normal upper values or creatinine clearance ≥50 milliliters/minute, bilirubin ≤1.25 times upper normal values, ratio aspartate transaminase/alanine transaminase (AST/ALT) ≤1.5 times the upper normal values (≤5 times the upper normal values for patients with liver metastases)
- •No unstable conditions: myocardial infarction within 6 months prior to the start of the study, congestive heart failure, unstable angina, active cardiomyopathy, unstable rhythm disorder, uncontrolled hypertension, uncontrolled psychiatric disorders, severe infection, peptic ulcer or any condition that could be aggravated by treatment or limit compliance (investigator assessment)
- •Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 7 days prior to the start of study drug.
- •Women of childbearing potential should use an adequate method of contraception to avoid pregnancy during nivolumab treatment until 5 months after the last dose of investigational drug.
排除标准
- •Ovarian cancer in first-line
- •First platinum sensitive relapse amenable to initial cytoreduction surgery
- •History of breast cancer or previous malignancies within 5 years prior to inclusion, with the exception of radically excised basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
- •Subjects who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded
- •Patients with active coronary artery disease
- •Patients with known acute hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive, that might affect host immunity
- •Patients with known pre-existent auto-immune disease
- •Patients with severe restrictive or obstructive pulmonary disease
- •Known carboplatin or cisplatin allergy
- •Life expectancy less than 3 months
- •Extraperitoneal metastases for which the site or number preclude potentially curative surgery at any moment during the course of the disease
- •Sign of bowel obstruction or lesions whose topography indicates a risk of intestinal perforation or inflammatory bowel disease
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) 3-4
- •Contraindication to the placement of an intraperitoneal catheter
- •peripheral sensory neuropathy grade at least 2
- •Patient with myelodysplastic syndrome/acute myeloid leukemia history.
- •Major surgery within 4 weeks of starting study treatment and patient must have recovered from any effects of any major surgery.
- •Previous allogenic bone marrow transplant
- •Any previous treatment with Anti programmed cell death 1 (PD-1) immunotherapy
- •Pregnant or lactating women
- •Unable to give consent
- •Patient under legal protection measures
- •Refusal to participate in the study
研究组 & 干预措施
Treatment Group
Intraperitoneal (IP) nivolumab treatment, after extensive debulking surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
干预措施: Intraperitoneal (IP) nivolumab infusion (Drug)
结局指标
主要结局
Safety profile of the Intraperitoneal (IP) nivolumab treatment
时间窗: 28 days
Safety profile of the Intraperitoneal (IP) nivolumab treatment, after extensive debulking surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC), as defined by the maximal dose for which a Dose-Limiting Toxicity (DLT) will be observed in no more than 1 patient out of 6 patients included at the respective dose-level.
次要结局
- Changes over time in disease progression(Measure taken at 1 month, 3 months, 6 months)
- Changes in toxicity as assessed by the Common Terminology Criteria (CTC) scale- Surgery(Measure taken at Day 5, Day 20, Day 35, and Day 50 after Surgery)
- Changes over time in toxicity as assessed by the Common Terminology Criteria (CTC) scale- Intraperitoneal (IP) nivlumab infusion(Measure taken at 1 month, 3 months and 6 months after the last IP nivlumab infusion)
- Changes in tolerance of post procedure intravenous (IV) chemotherapy- Surgery(Measure taken at Day 5, Day 20, Day 35, and Day 50 after surgery)
- Changes over time in tolerance of post procedure intravenous (IV) chemotherapy- Intraperitoneal (IP) nivlumab infusion(Measure taken at 1 month, 3 months and 6 months after the last IP nivlumab infusion)