Back to resultsTolerance of Intraperitoneal (IP) Nivolumab After Extensive Debulking Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients With Advanced Ovarian Carcinoma (ICONIC)
Primary Purpose
Ovarian Cancer
Status
Unknown status
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
Intraperitoneal (IP) nivolumab infusion
Sponsored by
About this trial
This is an interventional treatment trial for Ovarian Cancer focused on measuring Immunotherapy, Debulking surgery, Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
Sites / Locations
- Hospices Civils de Lyon
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment Group
Arm Description
Intraperitoneal (IP) nivolumab treatment, after extensive debulking surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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
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
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.
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03959761
Brief Title
Tolerance of Intraperitoneal (IP) Nivolumab After Extensive Debulking Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients With Advanced Ovarian Carcinoma
Acronym
ICONIC
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Unknown status
Study Start Date
July 31, 2019 (Anticipated)
Primary Completion Date
January 31, 2021 (Anticipated)
Study Completion Date
November 30, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer
Keywords
Immunotherapy, Debulking surgery, Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment Group
Arm Type
Experimental
Arm Description
Intraperitoneal (IP) nivolumab treatment, after extensive debulking surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)
Intervention Type
Drug
Intervention Name(s)
Intraperitoneal (IP) nivolumab infusion
Intervention Description
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
Primary Outcome Measure Information:
Title
Safety profile of the Intraperitoneal (IP) nivolumab treatment
Description
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
Secondary Outcome Measure Information:
Title
Changes over time in disease progression
Description
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
Title
Changes in toxicity as assessed by the Common Terminology Criteria (CTC) scale- Surgery
Description
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
Title
Changes over time in toxicity as assessed by the Common Terminology Criteria (CTC) scale- Intraperitoneal (IP) nivlumab infusion
Description
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
Title
Changes in tolerance of post procedure intravenous (IV) chemotherapy- Surgery
Description
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
Title
Changes over time in tolerance of post procedure intravenous (IV) chemotherapy- Intraperitoneal (IP) nivlumab infusion
Description
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
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gilles FREYER, PhD
Phone
4.78.86.43.18
Ext
33
Email
gilles.freyer@chu-lyon.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Nadjat MEDEGHRI
Phone
4.78.86.41.18
Ext
33
Email
nadjat.medeghri@chu-lyon.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilles FREYER, PhD
Organizational Affiliation
Hospices Civils de Lyon
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospices Civils de Lyon
City
Lyon
ZIP/Postal Code
69002
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gilles FREYER, PhD
Phone
4.78.86.43.18
Ext
33
Email
gilles.freyer@chu-lyon.fr
First Name & Middle Initial & Last Name & Degree
Nadjat MEDEGHRI
Phone
4.78.86.41.18
Ext
33
Email
nadjat.medeghri@chu-lyon.fr
12. IPD Sharing Statement
Learn more about this trial
Tolerance of Intraperitoneal (IP) Nivolumab After Extensive Debulking Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients With Advanced Ovarian Carcinoma
We'll reach out to this number within 24 hrs