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

NCT03959761 | Completed Phase 1 DMC

• 2 other identifiers: 69HCL18_08022018-004408-21
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Ovarian Cancer

Keywords

Immunotherapy; Debulking surgery; Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

Outcome Measures

Primary Outcomes (1)

• 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.

  28 days

Secondary Outcomes (5)

• 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

Study Arms (1)

Treatment Group

EXPERIMENTAL

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

Drug: Intraperitoneal (IP) nivolumab infusion

Interventions

Intraperitoneal (IP) nivolumab infusion DRUG

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

Treatment Group

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Ovarian cancer in first-line
• First platinum sensitive relapse amenable to initial cytoreduction surgery
• 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.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hospices Civils de Lyon

Lyon, 69002, France

Location

Related Publications (1)

• Corbaux P, Freyer G, Glehen O, You B, Bakrin N, Gelot A, Dayde D, Sajous C, Piffoux M, Peron J, Lescuyer G, Payen L, Kepenekian V. Intraperitoneal Nivolumab after Debulking Surgery and Hyperthermic Intraperitoneal Chemotherapy in Advanced Ovarian Cancer: A Phase I Study with Expansion Cohort. Clin Cancer Res. 2024 Aug 15;30(16):3438-3446. doi: 10.1158/1078-0432.CCR-24-0507.

  PMID: 38819408 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Infusions, Parenteral

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Gilles FREYER, PhD

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2019
• First Posted: May 22, 2019
• Study Start: October 17, 2019
• Primary Completion: October 3, 2022
• Study Completion: October 3, 2022
• Last Updated: December 19, 2025

Record last verified: 2025-12

Locations

FR (1)