Intraoperative Intraperitoneal Chemoperfusion to Treat Peritoneal Minimal Residual Disease in Stage III Ovarian Cancer

NCT ID: NCT02567253

Last Updated: 2023-11-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

56 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-03-31

Study Completion Date

2021-08-25

Brief Summary

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The OvIP1 study is designed to examine how drug dose and perfusion temperature affect the pharmacokinetics and pharmacodynamics of cisplatin used as (hyperthermic) intraperitoneal chemoperfusion, as an adjunct to surgery, in women with stage III epithelial ovarian cancer.

Detailed Description

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Stage III ovarian cancer (OC) remains an important cause of cancer related mortality in women. After successful initial treatment, most patients eventually develop recurrent peritoneal disease which can only arise from peritoneal minimal residual disease (pMRD) left after primary cytoreductive surgery (CRS). Intensification of locoregional therapy through intraoperative intraperitoneal chemoperfusion (IPEC) immediately following CRS may prevent or delay peritoneal recurrence. Although IPEC, usually under hyperthermic conditions, is increasingly used in OC, its efficacy and the potential benefit of hyperthermia are at present unknown.The primary aim of this study is to assess the pharmacokinetic and pharmacodynamic properties of IP cisplatin administered under normothermic or hyperthermic conditions, and at different dosing schedules. Additional endpoints include surgery related morbidity and mortality, quality of life, overall survival, disease free survival, peritoneal recurrence free survival, peritoneal cytology, and exploration of potential biomarkers.

Conditions

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Ovarian Cancer Primary Peritoneal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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low dose, normothermic

CRS + normothermic (37°C) intraoperative intraperitoneal chemoperfusion, with 75mg/m² Cisplatin during 90min + adjuvant chemotherapy

Group Type EXPERIMENTAL

Cytoreductive surgery

Intervention Type PROCEDURE

Complete or nearly complete (CC-0 or CC-1) macroscopic cytoreduction at the time of surgery of peritoneal carcinomatosis from ovarian cancer

IPEC with Cisplatin (75mg/m²)

Intervention Type DRUG

Intraperitoneal normotherm (37°C) administration of Cisplatin (75mg/m²) , during 90min

high dose, normothermic

CRS + normothermic (37°C) intraoperative intraperitoneal chemoperfusion, with 100mg/m² Cisplatin during 90min + adjuvant chemotherapy

Group Type EXPERIMENTAL

Cytoreductive surgery

Intervention Type PROCEDURE

Complete or nearly complete (CC-0 or CC-1) macroscopic cytoreduction at the time of surgery of peritoneal carcinomatosis from ovarian cancer

IPEC with Cisplatin (100mg/m²)

Intervention Type DRUG

Intraperitoneal normotherm (37°C) administration of Cisplatin (100mg/m²), during 90min

low dose, hyperthermic

CRS + hyperthermic (41°C) intraoperative intraperitoneal chemoperfusion, with 75mg/m² Cisplatin during 90min + adjuvant chemotherapy

Group Type EXPERIMENTAL

Cytoreductive surgery

Intervention Type PROCEDURE

Complete or nearly complete (CC-0 or CC-1) macroscopic cytoreduction at the time of surgery of peritoneal carcinomatosis from ovarian cancer

Hypertherm IntraPEritoneal Chemotherapy with Cisplatin (75mg/m²)

Intervention Type DRUG

Intraperitoneal hypertherm (41°C) administration of Cisplatin (75mg/m²), during 90min

high dose, hyperthermic

CRS + hyperthermic (41°C) intraoperative intraperitoneal chemoperfusion, with 100mg/m² Cisplatin during 90min + adjuvant chemotherapy

Group Type EXPERIMENTAL

Cytoreductive surgery

Intervention Type PROCEDURE

Complete or nearly complete (CC-0 or CC-1) macroscopic cytoreduction at the time of surgery of peritoneal carcinomatosis from ovarian cancer

HIPEC with Cisplatin (100mg/m²)

Intervention Type DRUG

Intraperitoneal hypertherm (41°C) administration of Cisplatin (100mg/m²), during 90min

Interventions

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Cytoreductive surgery

Complete or nearly complete (CC-0 or CC-1) macroscopic cytoreduction at the time of surgery of peritoneal carcinomatosis from ovarian cancer

Intervention Type PROCEDURE

IPEC with Cisplatin (75mg/m²)

Intraperitoneal normotherm (37°C) administration of Cisplatin (75mg/m²) , during 90min

Intervention Type DRUG

IPEC with Cisplatin (100mg/m²)

Intraperitoneal normotherm (37°C) administration of Cisplatin (100mg/m²), during 90min

Intervention Type DRUG

Hypertherm IntraPEritoneal Chemotherapy with Cisplatin (75mg/m²)

Intraperitoneal hypertherm (41°C) administration of Cisplatin (75mg/m²), during 90min

Intervention Type DRUG

HIPEC with Cisplatin (100mg/m²)

Intraperitoneal hypertherm (41°C) administration of Cisplatin (100mg/m²), during 90min

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Tumor type:

\* Biopsy proven serous epithelial ovarian carcinoma or peritoneal carcinoma
* Primary or recurrent disease
* Extent of disease:

* Positive retroperitoneal lymph nodes and /or microscopic metastasis beyond the pelvis (FIGO stage III, Appendix (47))
* Stage IV with unilateral pleural fluid allowed
* Complete or nearly complete macroscopic cytoreduction at the time of surgery (CC-0 or CC-1) deemed possible based on imaging, laparoscopy, or both
* Second-line patients; platinum sensitive
* Age over 18 years
* No major cardiac or respiratory disease
* Adequate performance status (Karnofsky index \> 70%)
* Adequate mental faculty, allowing to understand the proposed treatment protocol and provide informed consent
* Expected life expectancy more than 6 months
* Laboratory data:

* Serum creatinine ≤ 1.5 mg/dl or a calculated Glomerular Filtration Rate (GFR) (CKD-EPI) ≥ 60 mL/min/1.73 m2
* Serum total bilirubin ≤ 1.5 mg/dl, except for known Gilbert's disease
* Platelet count \> 100.000/µl
* Hemoglobin \> 9g/dl
* Neutrophil granulocytes \> 1.500/ml
* International Normalized Ratio (INR) ≤ 2
* Absence of alcohol and/or drug abuse
* No other concurrent malignant disease
* No inclusion in other clinical trials interfering with the study protocol
* No concurrent chronic systemic immune or hormone therapy, except neoadjuvant chemotherapy
* Absence of any severe organ insufficiency
* No pregnancy or breast feeding
* Written informed consent

Exclusion Criteria

* Severe or uncontrolled cardiac insufficiency, including recent (\< 6 months) occurrence of myocardial infarction, the presence of congestive cardiac insufficiency, of symptomatic angor in spite of optimal medical care, of cardiac arrhythmia requiring medical treatment presenting insufficient rhythm control, or uncontrolled arterial hypertension
* Pregnancy or breast feeding
* Platinum resistant or refractory disease
* Active bacterial, viral or fungal infection
* Active gastro-duodenal ulcer
* Parenchymal liver disease (any stage cirrhosis)
* Uncontrolled diabetes mellitus
* Severe obstructive or restrictive respiratory insufficiency
* Psychiatric pathology capable of affecting comprehension and judgment faculty
* Tumor in the presence of obstruction
* Evidence of extra-abdominal disease (with the exception of unilateral malignant pleural effusion) or extensive liver metastasis
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Ghent

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Wim P Ceelen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Ghent

Locations

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UZ Ghent

Ghent, East-Flanders, Belgium

Site Status

Countries

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Belgium

References

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Coleman RL, Monk BJ, Sood AK, Herzog TJ. Latest research and treatment of advanced-stage epithelial ovarian cancer. Nat Rev Clin Oncol. 2013 Apr;10(4):211-24. doi: 10.1038/nrclinonc.2013.5. Epub 2013 Feb 5.

Reference Type BACKGROUND
PMID: 23381004 (View on PubMed)

Foley OW, Rauh-Hain JA, del Carmen MG. Recurrent epithelial ovarian cancer: an update on treatment. Oncology (Williston Park). 2013 Apr;27(4):288-94, 298.

Reference Type BACKGROUND
PMID: 23781692 (View on PubMed)

Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, Copeland LJ, Walker JL, Burger RA; Gynecologic Oncology Group. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006 Jan 5;354(1):34-43. doi: 10.1056/NEJMoa052985.

Reference Type BACKGROUND
PMID: 16394300 (View on PubMed)

Markman M, Bundy BN, Alberts DS, Fowler JM, Clark-Pearson DL, Carson LF, Wadler S, Sickel J. Phase III trial of standard-dose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol. 2001 Feb 15;19(4):1001-7. doi: 10.1200/JCO.2001.19.4.1001.

Reference Type BACKGROUND
PMID: 11181662 (View on PubMed)

Alberts DS, Liu PY, Hannigan EV, O'Toole R, Williams SD, Young JA, Franklin EW, Clarke-Pearson DL, Malviya VK, DuBeshter B. Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med. 1996 Dec 26;335(26):1950-5. doi: 10.1056/NEJM199612263352603.

Reference Type BACKGROUND
PMID: 8960474 (View on PubMed)

Jaaback K, Johnson N. Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer. Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005340. doi: 10.1002/14651858.CD005340.pub2.

Reference Type BACKGROUND
PMID: 16437527 (View on PubMed)

Kyrgiou M, Salanti G, Pavlidis N, Paraskevaidis E, Ioannidis JP. Survival benefits with diverse chemotherapy regimens for ovarian cancer: meta-analysis of multiple treatments. J Natl Cancer Inst. 2006 Nov 15;98(22):1655-63. doi: 10.1093/jnci/djj443.

Reference Type BACKGROUND
PMID: 17105988 (View on PubMed)

Ceelen WP, Van Nieuwenhove Y, Van Belle S, Denys H, Pattyn P. Cytoreduction and hyperthermic intraperitoneal chemoperfusion in women with heavily pretreated recurrent ovarian cancer. Ann Surg Oncol. 2012 Jul;19(7):2352-9. doi: 10.1245/s10434-009-0878-6. Epub 2009 Dec 29.

Reference Type BACKGROUND
PMID: 20039210 (View on PubMed)

Issels RD. Hyperthermia adds to chemotherapy. Eur J Cancer. 2008 Nov;44(17):2546-54. doi: 10.1016/j.ejca.2008.07.038. Epub 2008 Sep 11.

Reference Type BACKGROUND
PMID: 18789678 (View on PubMed)

Sun X, Li XF, Russell J, Xing L, Urano M, Li GC, Humm JL, Ling CC. Changes in tumor hypoxia induced by mild temperature hyperthermia as assessed by dual-tracer immunohistochemistry. Radiother Oncol. 2008 Aug;88(2):269-76. doi: 10.1016/j.radonc.2008.05.015. Epub 2008 Jun 5.

Reference Type BACKGROUND
PMID: 18538874 (View on PubMed)

Bijelic L, Jonson A, Sugarbaker PH. Systematic review of cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy for treatment of peritoneal carcinomatosis in primary and recurrent ovarian cancer. Ann Oncol. 2007 Dec;18(12):1943-50. doi: 10.1093/annonc/mdm137. Epub 2007 May 11.

Reference Type BACKGROUND
PMID: 17496308 (View on PubMed)

Helm CW. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer. Oncologist. 2009 Jul;14(7):683-94. doi: 10.1634/theoncologist.2008-0275. Epub 2009 Jul 16.

Reference Type BACKGROUND
PMID: 19608639 (View on PubMed)

de Bree E, Helm CW. Hyperthermic intraperitoneal chemotherapy in ovarian cancer: rationale and clinical data. Expert Rev Anticancer Ther. 2012 Jul;12(7):895-911. doi: 10.1586/era.12.72.

Reference Type BACKGROUND
PMID: 22845405 (View on PubMed)

Mulier S, Claes JP, Dierieck V, Amiel JO, Pahaut JP, Marcelis L, Bastin F, Vanderbeeken D, Finet C, Cran S, Velu T. Survival benefit of adding Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) at the different time-points of treatment of ovarian cancer: review of evidence. Curr Pharm Des. 2012;18(25):3793-803. doi: 10.2174/138161212802002616.

Reference Type BACKGROUND
PMID: 22591422 (View on PubMed)

Other Identifiers

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AGO/2015/002

Identifier Type: -

Identifier Source: org_study_id