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Ovarian CancerPhase 1/2ICONICNCT03959761

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

A Phase 1/2 study testing Intraperitoneal (IP) nivolumab infusion in people with Ovarian Cancer, run by Hospices Civils de Lyon at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Ovarian Cancer
What is being tested?
Intraperitoneal (IP) nivolumab infusion
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
1 siteFrance
Study dates
17 Oct 2019to 3 Oct 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

France1 site

  • Hospices Civils de Lyon

    Lyon, 69002

Other trials in France

About this study

Official title: 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

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.

Read more

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
Being tested
Intraperitoneal (IP) nivolumab infusion
Keywords
Immunotherapy, Debulking surgery, Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
Medical subject headings
Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Intraperitoneal (IP) nivolumab infusionDrug

    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
Study groups in NCT03959761
Study groupRoleWhat they receive
Treatment GroupExperimentalIntraperitoneal (IP) nivolumab treatment, after extensive debulking surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
Receives: Drug: Intraperitoneal (IP) nivolumab infusion

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 28 days

Secondary outcomes (5)

  1. 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.

    Measured: Measure taken at 1 month, 3 months, 6 months

  2. 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

    Measured: Measure taken at Day 5, Day 20, Day 35, and Day 50 after Surgery

  3. 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

    Measured: Measure taken at 1 month, 3 months and 6 months after the last IP nivlumab infusion

  4. 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.

    Measured: Measure taken at Day 5, Day 20, Day 35, and Day 50 after surgery

  5. 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

    Measured: Measure taken at 1 month, 3 months and 6 months after the last IP nivlumab infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 May 2019
  2. Study start17 Oct 2019
  3. Primary completion3 Oct 2022
  4. Study completion3 Oct 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03959761
Sponsor's protocol ID
69HCL18_0802
Other IDs
2018-004408-21, 2018
Acronym
ICONIC
Status last verified
Dec 2025
First submitted
21 May 2019
Last updated
19 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 38819408

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Intraperitoneal (IP) nivolumab infusion in people with Ovarian Cancer, run by Hospices Civils de Lyon at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety profile of the Intraperitoneal (IP) nivolumab treatment (time frame: 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03959761, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2025.

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