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Ovarian CancerPhase 2OvIP1NCT02567253

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

A Phase 2 study testing Cytoreductive surgery, IPEC with Cisplatin (75mg/m²) and IPEC with Cisplatin (100mg/m²) in people with Ovarian Cancer and Primary Peritoneal Cancer, run by University Hospital, Ghent at 1 site in Belgium.

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

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. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Ovarian Cancer, Primary Peritoneal Cancer
What is being tested?
Cytoreductive surgery, IPEC with Cisplatin (75mg/m²) and IPEC with Cisplatin (100mg/m²)
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
56 participants
Where
1 siteBelgium
Study dates
Mar 2016to 25 Aug 2021
Phase
Phase 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

  • 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
Show all 27Show fewer
  • 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

Who cannot join

  • 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)
Show all 11Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Belgium1 site

  • UZ Ghent

    Ghent, East-Flanders, 9000

Other trials in Belgium

About this study

Official title: Intraoperative Intraperitoneal Chemoperfusion to Treat Peritoneal Minimal Residual Disease in Stage III Ovarian Cancer: A Randomized Phase II Trial

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.

Read the detailed description

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.

Being tested
Cytoreductive surgery, IPEC with Cisplatin (75mg/m²), IPEC with Cisplatin (100mg/m²), Hypertherm IntraPEritoneal Chemotherapy with Cisplatin (75mg/m²), HIPEC with Cisplatin (100mg/m²)
Keywords
Cytoreductive surgery, (H)ipec, Ovarian cancer, Cisplatin, Peritoneal carcinomatosis, Pharmacokinetics, Pharmacodynamics
Medical subject headings
Ovarian Neoplasms, Peritoneal Neoplasms

What participants receive

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

  • Cytoreductive surgeryProcedure or surgery

    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)Drug

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

  • IPEC with Cisplatin (100mg/m²)Drug

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

  • Hypertherm IntraPEritoneal Chemotherapy with Cisplatin (75mg/m²)Drug

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

  • HIPEC with Cisplatin (100mg/m²)Drug

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

Study groups in NCT02567253
Study groupRoleWhat they receive
low dose, normothermicExperimentalCRS + normothermic (37°C) intraoperative intraperitoneal chemoperfusion, with 75mg/m² Cisplatin during 90min + adjuvant chemotherapy
Receives: Procedure: Cytoreductive surgery; Drug: IPEC with Cisplatin (75mg/m²)
high dose, normothermicExperimentalCRS + normothermic (37°C) intraoperative intraperitoneal chemoperfusion, with 100mg/m² Cisplatin during 90min + adjuvant chemotherapy
Receives: Procedure: Cytoreductive surgery; Drug: IPEC with Cisplatin (100mg/m²)
low dose, hyperthermicExperimentalCRS + hyperthermic (41°C) intraoperative intraperitoneal chemoperfusion, with 75mg/m² Cisplatin during 90min + adjuvant chemotherapy
Receives: Procedure: Cytoreductive surgery; Drug: Hypertherm IntraPEritoneal Chemotherapy with Cisplatin (75mg/m²)
high dose, hyperthermicExperimentalCRS + hyperthermic (41°C) intraoperative intraperitoneal chemoperfusion, with 100mg/m² Cisplatin during 90min + adjuvant chemotherapy
Receives: Procedure: Cytoreductive surgery; Drug: HIPEC with Cisplatin (100mg/m²)

What is being measured

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

  1. Tissue penetration distance of cisplatin in peritoneal tumor tissue nodules using laser-ablation inductively couples plasma mass spectrometry

    This will be analyzed via laser ablation-inductively coupled plasma- mass spectrometry (LA-ICP-MS)

    Measured: 1 tumor nodule will be immediately fixed in liquid nitrogen after cytoreductive surgery and chemoperfusion. Frozen sections will be ablated through study completion

Secondary outcomes (11)

  1. Surgical morbidity and mortality will be measured using Dindo-Clavien classification

    This will be estimated with the Dindo-Clavien classification

    Measured: Within 30 days after surgery and intraoperative intraperitoneal chemoperfusion

  2. Cancer-specific Quality of Life-C30

    This will be investigated using the cancer-specific (C30) European Organization for Research and Treatment of Cancer (EORTC) Quality of Life questionnaires

    Measured: 3 weeks before operation, 6 weeks after and 3, 6, 12, 18 and 24 months after surgery and chemoperfusion

  3. Disease-specific Quality of Life-OV28

    This will be investigated using the disease-specific (OV28) European Organization for Research and Treatment of Cancer (EORTC) Quality of Life questionnaires

    Measured: 3 weeks before operation, 6 weeks after and 3, 6, 12, 18 and 24 months after surgery and chemoperfusion

  4. Maximum perfusate concentration (Cmax) of cisplatin

    Cisplatin (free + bounded) will be measured in perfusate, using high performance liquid chromatography coupled to an inductively coupled plasma- mass spectrometry (HPLC-ICP-MS)

    Measured: T=0min (before chemoperfusion), T=15min, T=30min, T=90min (during chemoperfusion); T=2h, T=3h, T=7.5h, T=24h (after start chemoperfusion)

  5. Maximum plasma concentration (Cmax) and Area Under The Curve (AUC) of cisplatin

    Cisplatin (free + bounded) will be measured in plasma, using high performance liquid chromatography coupled to an inductively coupled plasma- mass spectrometry (HPLC-ICP-MS)

    Measured: T=0min (before chemoperfusion); T=15min, T=30min, T=90min (during chemoperfusion); T=2h, T=3h, T=7.5h, T=24h (after start chemoperfusion)

  6. Pharmacodynamics (PD) of cisplatin will be analyzed by visualizing the amount of DNA double-strand breaks (dsb) via the specific DNA-adduct immunohistochemical Liedert staining

    PD of cisplatin will be studied via Pt-DNA adduct formation, using the Liedert staining which is specific for Pt-[Guanine, Guanine] adducts (Pt-[GG]) using Mab R-C18. The amount of double-strand breaks (dsb) will be analyzed then via fluorescence microscopy

    Measured: 1 tumor nodule will be immediately fixed in 4% paraformaldehyde and immunohistochemical stainings will be done through study completion

  7. Overall survival

    Calculated from date of surgery until death

    Measured: 24 months after finishing the adjuvant chemotherapy

  8. Disease free survival

    Time interval between date of surgery and disease progression or death

    Measured: 24 months after finishing the adjuvant chemotherapy

  9. Peritoneal recurrence free survival

    Time interval between date of surgery and peritoneal recurrence or death

    Measured: 24 months after finishing the adjuvant chemotherapy

  10. Expression analysis of selected biomarkers = Excision repair cross-complementation group 1 (ERCC1), Methylguanine methyltransferase enzyme (MGMT), Breast cancer gene 1 (BRCA1), Copper transporter 1 (CTR1) using quantitative PCR

    Gene expression of potential predictive biomarkers using qPCR

    Measured: 1 tumor nodule will be immediately fixed in liquid nitrogen. Histological coupes will be made through study completion

  11. Stromal composition and density of tumor tissues via analyzing collagen density, fibroblast Proliferation and DNA-intrastrand adduct formation of Pt-[GG]

    Analyzing collagen density using the sirius red staining, analyzing fibroblast proliferation using alfa smooth-muscle action (α-SMA) stainings and DNA intrastrand adduct formation of Pt-[GG] with the Liedert staining using Mab R-C18

    Measured: 1 tumor nodule will be immediately fixed in 4% paraformaldehyde. Histological coupes will be made through study completion

Timeline

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

  1. First posted2 Oct 2015 (estimated)
  2. Study startMar 2016
  3. Primary completion31 Dec 2020
  4. Study completion25 Aug 2021

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
56 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02567253
Sponsor's protocol ID
AGO/2015/002
Acronym
OvIP1
Status last verified
Nov 2023
First submitted
23 Sep 2015
Last updated
27 Nov 2023
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 23381004

  • 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.

    PubMed 23781692

  • 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.

    PubMed 16394300

  • 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.

    PubMed 11181662

  • 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.

    PubMed 8960474

  • 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.

    PubMed 16437527

  • 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.

    PubMed 17105988

  • 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.

    PubMed 20039210

  • 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.

    PubMed 18789678

  • 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.

    PubMed 18538874

  • 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.

    PubMed 17496308

  • 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.

    PubMed 19608639

  • 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.

    PubMed 22845405

  • 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.

    PubMed 22591422

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cytoreductive surgery, IPEC with Cisplatin (75mg/m²) and IPEC with Cisplatin (100mg/m²) in people with Ovarian Cancer and Primary Peritoneal Cancer, run by University Hospital, Ghent at 1 site in Belgium.

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 27 inclusion and 11 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 27 Nov 2023. 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 Belgium. 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 phase mean?

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?

Tissue penetration distance of cisplatin in peritoneal tumor tissue nodules using laser-ablation inductively couples plasma mass spectrometry (time frame: 1 tumor nodule will be immediately fixed in liquid nitrogen after cytoreductive surgery and chemoperfusion. Frozen sections will be ablated through study completion). 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 NCT02567253, which also lists 14 linked publications.

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 27 Nov 2023.

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