Hyperthermic Intraoperative Intraperitoneal Chemotherapy of Recurrent Ovarian Cancer - A Feasibility Study

Study Description

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Brief Summary:

Most studies performing hyperthermic intraoperative intraperitoneal chemotherapy dose the cytotoxic drugs according to the body surface (like 50 mg/m² cisplatin) in analogy to systemic, intravenous chemotherapy (usually using the same dose). Although there seems to be a correlation between body surface and blood volume, the pharmacodynamics of drugs dosed by the body surface is still highly variable and thus dosing on the body surface is increasingly considered controversial for systemic administration.

For hyperthermic intraoperative intraperitoneal chemotherapy dosing by the body surface makes even less sense, since the aim is the highest possible drug concentration in the peritoneum without undue local and systemic toxicity. Furthermore, most studies using intraoperative chemotherapy vary the volume of the perfusate according to the size of the patient. Since the amount of cytotoxic drug is already fixed by the dosing on the body surface (amount [mg] = dose [mg/m²] x body surface [m²]) the effective concentration (mg/l) in the perfusate can vary considerably between patients. On the other hand pharmacokinetic analyses have shown that reducing the concentration of the cytotoxic drug in the perfusate reduces the efficacy even if the amount of the drug remains the same.

In this study the safety of a new dosing regime will be evaluated. The concentration of cisplatin in the perfusate will be held constant independent of body weight or size to achieve the highest effectiveness of the chemotherapy. The primary endpoint is the safety of the treatment. All patients should be able to receive full dose systemic carboplatin chemotherapy after completion the trial treatment.

Condition or disease	Intervention/treatment	Phase
Epithelial Ovarian Cancer; Fallopian Tube Carcinoma	Procedure: Hyperthermic intraoperative intraperitoneal chemotherapy; Procedure: Cytoreduction; Drug: Cisplatin	Not Applicable

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Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	6 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Hyperthermic Intraoperative Intraperitoneal Chemotherapy of Recurrent Ovarian Cancer - A Feasibility Study
Study Start Date :	February 2008
Actual Primary Completion Date :	December 2011
Actual Study Completion Date :	December 2012

Arms and Interventions

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Arm

Intervention/treatment

Experimental: HIPEC treatment; Cytoreduction Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) with cisplatin Perfusion of the peritoneum with 42°C warm 25 mg/l cisplatin solution. Perfusion volume depends on body size (3 - 6 l). If cisplatin amount exceeds the equivalent of 62.5 mg/m² body surface, cisplatin is dosed by body surface (62.5 mg/m²)(safety margin). Perfusion is performed with the open or Coliseum technique for 90 min.

Procedure: Hyperthermic intraoperative intraperitoneal chemotherapy; Perfusion of the peritoneum with 42°C warm 25 mg/l cisplatin solution.; Other Name: HIPEC Procedure: Cytoreduction; Surgical removal of tumor nodules including resection of organs infested with tumor Drug: Cisplatin; Cisplatin is applied as chemotherapy during surgery; Other Names: cis-diamminedichloroplatinum(II); cisplatinum; CDDP; Platinol

Outcome Measures

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Primary Outcome Measures :

1. Fitness for Systemic Chemotherapy [ Time Frame: 3 months post operation ]

   Are patients fit to receive six courses of systemic carboplatin chemotherapy after completion of trial.

   If chemotherapy starts within 3 months after surgery and at least 4 courses could be administered, patient is considered fit.

   If chemotherapy is stopped early for reasons clearly unrelated to study treatment (e.g. platinum resistance), patient is also considered fit.

Secondary Outcome Measures :

1. Nephrotoxicity [ Time Frame: 6 weeks post operation ]
   glomerular filtration rate (GFR)
2. Surgical Complications [ Time Frame: 6 weeks post operation ]
   any serious surgical event (Dindo scale >= III (reoperation required) or CTCAE grade >=3)
3. Overall Survival [ Time Frame: 5 years ]
4. Pharmacokinetics [ Time Frame: intraoperative and 1 week after surgery ]
   data not analysed due to poor accrual

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Patient with histologically confirmed and recurrent epithelial ovarian carcinoma, fallopian tube carcinoma or primary peritoneal carcinoma requiring secondary debulking. Last chemotherapy of primary treatment was finished at least 6 months before.
• Patient must give written informed consent before registration
• WHO/ECOG performance status 0 - 1
• Age ≥18 years, ≤70 years
• Adequate hematological values: leukocytes ≥3x10^9/l, thrombocytes ≥100x10^9/l
• Adequate renal function. Obstructive hydronephrosis as a cause of "borderline" (30 - 45 ml/min) renal function should be investigated and treated prior to study entry.
• Patient compliance and geographic proximity allow proper staging and follow-up.
• FIGO III and IV

Exclusion Criteria:

• Primary diagnosis of epithelial ovarian cancer, or primary treatment completed less than 6 months ago.
• FIGO stage I + II
• Distant and current metastases
• WHO/ECOG performance status ≥2
• Inadequate hepatic function: bilirubin >1.5x ULN (upper limit normal range) or ASAT/ALAT >2.5x ULN or AP >5x ULN
• Psychiatric disorder precluding understanding of information of trial related topics or giving informed consent
• Concurrent treatment with other experimental drugs or other anti-cancer therapy, treatment in a clinical trial within 30 days prior to trial entry
• Any serious underlying medical condition (at the judgment of the investigator) which could impair the ability of the patient to participate in the trial (e.g. active autoimmune disease, uncontrolled diabetes)
• Known hypersensitivity to cisplatin
• Any concomitant drugs contraindicated for use with the trial drugs according to the Swissmedic-approved product information
• Dehydration
• Impaired hearing or symptomatic peripheral neuropathy: ≥grade II NCI-CTCAEv3
• Regular use of anti-epileptics

Contacts and Locations

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Locations

Switzerland
Department of Surgery, Cantonal Hospital St. Gallen
St. Gallen, Switzerland, 9007

Sponsors and Collaborators

Cantonal Hospital of St. Gallen

Investigators

Principal Investigator:	Markus Lüdin, MD	Cantonal Hospital St. Gallen, Department of Surgery

More Information

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Additional Information:

Department of Surgery, Cantonal Hospital St. Gallen, Switzerland 

Responsible Party:	Sascha Müller, Oberarzt, Cantonal Hospital of St. Gallen
ClinicalTrials.gov Identifier:	NCT00968799 History of Changes
Other Study ID Numbers:	SGOV01
First Posted:	August 31, 2009
Results First Posted:	May 10, 2013
Last Update Posted:	May 15, 2013
Last Verified:	May 2013

Keywords provided by Sascha Müller, Cantonal Hospital of St. Gallen:

Ovarian Neoplasms; Recurrence; Hyperthermia, Induced	Peritoneal Neoplasms; recurrent epithelial ovarian cancer; recurrent fallopian tube carcinoma

Additional relevant MeSH terms:

Ovarian Neoplasms; Neoplasms, Glandular and Epithelial; Fever; Fallopian Tube Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female	Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Neoplasms by Histologic Type; Body Temperature Changes; Signs and Symptoms; Fallopian Tube Diseases; Cisplatin; Antineoplastic Agents