Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Symptoms and General Pathology

Wounds and Injuries

Behaviors and Mental Disorders

Rare Diseases

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hyperthermia

Fever

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Body Temperature Changes

Stress Disorders, Traumatic

Heat Stress Disorders

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Intraperitoneal (IP) nivolumab treatment, after extensive debulking surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

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

Intraperitoneal (IP) nivolumab infusion

Gilles FREYER, PhD

Nadjat MEDEGHRI

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.

Tolerance of Intraperitoneal (IP) Nivolumab After Extensive Debulking Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients With Advanced Ovarian Carcinoma

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

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.

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.

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

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.

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

Hospices Civils de Lyon

Spots Global Cancer Trial Database for intraperitoneal (ip) nivolumab infusion