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

This study has been terminated.
(poor patient accrual)
Sponsor:
Information provided by (Responsible Party):
Sascha Müller, Cantonal Hospital of St. Gallen
ClinicalTrials.gov Identifier:
NCT00968799
First received: February 12, 2008
Last updated: May 13, 2013
Last verified: May 2013
  Purpose

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 Intervention
Epithelial Ovarian Cancer
Fallopian Tube Carcinoma
Procedure: Hyperthermic intraoperative intraperitoneal chemotherapy
Procedure: Cytoreduction
Drug: Cisplatin

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Hyperthermic Intraoperative Intraperitoneal Chemotherapy of Recurrent Ovarian Cancer - A Feasibility Study

Resource links provided by NLM:


Further study details as provided by Cantonal Hospital of St. Gallen:

Primary Outcome Measures:
  • Fitness for Systemic Chemotherapy [ Time Frame: 3 months post operation ] [ Designated as safety issue: Yes ]

    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:
  • Nephrotoxicity [ Time Frame: 6 weeks post operation ] [ Designated as safety issue: Yes ]
    glomerular filtration rate (GFR)

  • Surgical Complications [ Time Frame: 6 weeks post operation ] [ Designated as safety issue: Yes ]
    any serious surgical event (Dindo scale >= III (reoperation required) or CTCAE grade >=3)

  • Overall Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Pharmacokinetics [ Time Frame: intraoperative and 1 week after surgery ] [ Designated as safety issue: No ]
    data not analysed due to poor accrual


Enrollment: 6
Study Start Date: February 2008
Study Completion Date: December 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00968799

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

Additional Information:
No publications provided

Responsible Party: Sascha Müller, Oberarzt, Cantonal Hospital of St. Gallen
ClinicalTrials.gov Identifier: NCT00968799     History of Changes
Other Study ID Numbers: SGOV01
Study First Received: February 12, 2008
Results First Received: March 26, 2013
Last Updated: May 13, 2013
Health Authority: Switzerland: Ethikkommission
Switzerland: Swissmedic

Keywords provided by Cantonal Hospital of St. Gallen:
Ovarian Neoplasms
Recurrence
Hyperthermia, Induced
Peritoneal Neoplasms
recurrent epithelial ovarian cancer
recurrent fallopian tube carcinoma

Additional relevant MeSH terms:
Carcinoma
Fever
Ovarian Neoplasms
Fallopian Tube Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Body Temperature Changes
Signs and Symptoms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 15, 2014