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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
22
Patients will be treated according to three dose-levels of nivolumab, starting 5 to 7 days after surgery + Hyperthermic Intraperitoneal Chemotherapy (HIPEC), through an Intraperitoneal (IP) catheter : * Level 1 : 0.5 milligrams/kilogram (mg/kg) IP infusion, repeated every 2 weeks for 4 infusions * Level 2 : 1 mg/kg IP infusion, repeated every 2 weeks for 4 infusions * Level 3 : 3 mg/kg IP infusion, repeated every 2 weeks for 4 infusions * Level -1 : 0,3 mg/kg IP infusion, repeated every 2 weeks for 4 infusions
Hospices Civils de Lyon
Lyon, France
Safety profile of the Intraperitoneal (IP) nivolumab treatment
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.
Time frame: 28 days
Changes over time in disease progression
Clinical diease progression is defined as the occurence and persistance of symptoms which are considered by the investigator as undoubtfully disease-related. Disease progression will be clinically evaluated using body imaging scans at different times after the last Intraperitoneal (IP) nivolumab injection.
Time frame: Measure taken at 1 month, 3 months, 6 months
Changes in toxicity as assessed by the Common Terminology Criteria (CTC) scale- Surgery
The National Cancer Institute created originally the Common Toxicity Criteria (CTC) to aid in the recognition and grading severity of adverse effects caused by chemotherapy treatments. The grading scale is as follows with grade 0 being no cancer and grade 5 being death: Grade Description Grade 0 (none) None Grade 1 (mild) Painless ulcers, erythema, or mild soreness in the absence of lesions Grade 2 (moderate) Painful erythema, oedema, or ulcers but eating or swallowing possible Grade 3 (severe) Painful erythema, oedema, or ulcers requiring intravenous (IV) hydration Grade 4 (life-threatening) Severe ulceration or requiring parenteral or enteral nutritional support or prophylactic intubation Grade 5 (death) Death related to toxicity
Time frame: 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
The National Cancer Institute created originally the Common Toxicity Criteria (CTC) to aid in the recognition and grading severity of adverse effects caused by chemotherapy treatments. The grading scale is as follows with grade 0 being no cancer and grade 5 being death: Grade Description Grade 0 (none) None Grade 1 (mild) Painless ulcers, erythema, or mild soreness in the absence of lesions Grade 2 (moderate) Painful erythema, oedema, or ulcers but eating or swallowing possible Grade 3 (severe) Painful erythema, oedema, or ulcers requiring intravenous (IV) hydration Grade 4 (life-threatening) Severe ulceration or requiring parenteral or enteral nutritional support or prophylactic intubation Grade 5 (death) Death related to toxicity
Time frame: 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
Patients will be clinically evaluated for any changes in tolerance to post procedure intravenous (IV) chemotherapy as defined by the appearance of any serious adverse events.
Time frame: 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
Patients will be clinically evaluated for any changes in tolerance to post procedure intravenous (IV) chemotherapy which includes any serious adverse events at different times after the last IP nivlumab infusion
Time frame: Measure taken at 1 month, 3 months and 6 months after the last IP nivlumab infusion
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