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

NCT02567253 | Completed Phase 2 DMC

• 1 other identifier: AGO/2015/002
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Ovarian Cancer; Primary Peritoneal Cancer

Keywords

Cytoreductive surgery; (H)ipec; Ovarian cancer; Cisplatin; Peritoneal carcinomatosis; Pharmacokinetics; Pharmacodynamics

Outcome Measures

Primary Outcomes (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)

  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)

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

  Within 30 days after surgery and intraoperative intraperitoneal chemoperfusion

• Cancer-specific Quality of Life-C30

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

• Disease-specific Quality of Life-OV28

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

• Maximum perfusate concentration (Cmax) of cisplatin

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

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

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

Study Arms (4)

low dose, normothermic

EXPERIMENTAL

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

Procedure: Cytoreductive surgery; Drug: IPEC with Cisplatin (75mg/m²)

high dose, normothermic

EXPERIMENTAL

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

Procedure: Cytoreductive surgery; Drug: IPEC with Cisplatin (100mg/m²)

low dose, hyperthermic

EXPERIMENTAL

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

Procedure: Cytoreductive surgery; Drug: Hypertherm IntraPEritoneal Chemotherapy with Cisplatin (75mg/m²)

high dose, hyperthermic

EXPERIMENTAL

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

Procedure: Cytoreductive surgery; Drug: HIPEC with Cisplatin (100mg/m²)

Interventions

Cytoreductive surgery PROCEDURE

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

high dose, hyperthermic; high dose, normothermic; low dose, hyperthermic; low dose, normothermic

IPEC with Cisplatin (75mg/m²) DRUG

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

low dose, normothermic

IPEC with Cisplatin (100mg/m²) DRUG

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

high dose, normothermic

Hypertherm IntraPEritoneal Chemotherapy with Cisplatin (75mg/m²) DRUG

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

low dose, hyperthermic

HIPEC with Cisplatin (100mg/m²) DRUG

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

high dose, hyperthermic

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Ghent: lead

Study Sites (1)

UZ Ghent

Ghent, East-Flanders, 9000, Belgium

Location

Related Publications (14)

• 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.

  PMID: 23381004 BACKGROUND

• 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.

  PMID: 23781692 BACKGROUND

• 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.

  PMID: 16394300 BACKGROUND

• 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.

  PMID: 11181662 BACKGROUND

• 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.

  PMID: 8960474 BACKGROUND

• 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.

  PMID: 16437527 BACKGROUND

• 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.

  PMID: 17105988 BACKGROUND

• 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.

  PMID: 20039210 BACKGROUND

• 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.

  PMID: 18789678 BACKGROUND

• 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.

  PMID: 18538874 BACKGROUND

• 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.

  PMID: 17496308 BACKGROUND

• 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.

  PMID: 19608639 BACKGROUND

• 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.

  PMID: 22845405 BACKGROUND

• 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.

  PMID: 22591422 BACKGROUND

MeSH Terms

Conditions

Ovarian Neoplasms; Peritoneal Neoplasms

Interventions

Cytoreduction Surgical Procedures; Cisplatin; Hyperthermic Intraperitoneal Chemotherapy

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; Abdominal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Peritoneal Diseases

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Chemotherapy, Adjuvant; Combined Modality Therapy; Therapeutics; Drug Therapy; Hyperthermia, Induced

Study Officials

• Wim P Ceelen, MD, PhD

  University Hospital, Ghent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2015
• First Posted: October 2, 2015
• Study Start: March 1, 2016
• Primary Completion: December 31, 2020
• Study Completion: August 25, 2021
• Last Updated: November 27, 2023

Record last verified: 2023-11

Locations

BE (1)