A Study With Intraperitoneal Cisplatin and Doxorubicin in Recurrent Ovarian Cancer and Peritoneal Carcinomatosis

Study Overview
=================
Brief Summary
-----------------
Fifteen women with recurrent ovarian cancer will be treated by an intraperitoneal chemotherapy with cisplatin and doxorubicin in three escalating dosage schedules. The aim of the study is to evaluate the safety and tolerability of doxorubicin and cisplatin every 4 weeks for three courses using a three-group, dose-escalation protocol with fixed dose-density. The time Frame for the assessment of the Primary outcome is therefore 12 weeks. Predefined toxicity criteria will be applied using CTCAE version 4.0 criteria. The study hypothesis is that local and systemic toxicity will increase with increasing dosage of cisplatin and doxorubicin during three repeated PIPAC courses with no CTCAE grade 4 and 5 events in any treatment group.

Detailed Description
-----------------
This is a prospective phase I, single-arm (nonrandomized), open-label, three step dose-escalation study with cisplatin and doxorubicin applied as PIPAC in 15 patients with recurrent ovarian cancer and peritoneal cancer. The first 5 patients will receive doxorubicin 1.5 mg/m2 body surface in 50 ml NaCl 0,9% and cisplatin 7.5 mg/m2 in 50 ml NaCl 0,9% q 4 weeks for three courses. The next 5 patients will receive doxorubicin 2.25 mg/m2 body surface in 50 ml NaCl 0,9% and cisplatin 11.25 mg/m2 in 50 ml NaCl 0,9% q 4 weeks for three courses. The next 5 patients will receive doxorubicin 3 mg/m2 body surface in 50 ml NaCl 0,9% and cisplatin 15 mg/m2 in 50 ml NaCl 0,9% q 4 weeks for three courses. This schedule represents a three-step, 50% dose-escalation. Dose density will not be changed. The aim of this study is to evaluate the safety and tolerability of doxorubicin and cisplatin every 4-6 weeks for three courses using a three-group, dose-escalation protocol with fixed dose-density. The time Frame for the assessment of the Primary outcome is therefore 12 weeks. Predefined toxicity criteria will be applied using CTCAE version 4.0 criteria, documented after the first, second, and third course of treatment. Clinical examinations will include abdominal computed tomography (CT) scans after the first, second, and third course of treatment, cardiac echocardiography before the first, second, and third course of treatment, and a clinical neurological assessment before the first, second, and third course of treatment. Pharmacological studies will include hematologic, liver, and renal function tests as well as cisplatin and doxorubicin plasma levels with blood samples drawn before, during, and up to 12 h after the start of each PIPAC course.

Official Title
-----------------
A Phase I, Single-arm, Open-label, Three Step Dose Escalation Study With Intraperitoneal Pressurized Cisplatin and Doxorubicin in Recurrent Ovarian Cancer and Peritoneal Carcinomatosis

Conditions
-----------------
Ovarian Cancer

Intervention / Treatment
-----------------
* Drug: Cisplatin and doxorubicin
* Procedure: Cisplatin and doxorubicin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: clinical and/or radiological evidence of PC, age between 18 and 85 years with a diagnosis of recurrent ovarian cancer with disease progression after at least one line of previous intravenous chemotherapy with a platinum compound, blood and electrolyte counts, liver, and renal function parameters within 10% of the normal range established in the respective laboratory of the study institution, provision of written informed consent, and postmenopausal status. Exclusion Criteria: extraabdominal metastatic disease, with the exception of isolated pleural carcinomatosis/effusion, chemotherapy or surgery within the last four weeks prior to the first PIPAC application, previous treatment with maximum cumulative doses of doxorubicin, daunorubicin, epirubicin, idarubicin, and/or other anthracyclines and anthracenediones, a history of allergic reaction to cisplatin or other platinum containing compounds or doxorubicin, severe renal impairment, myelosuppression, severe hepatic impairment, severe myocardial insufficiency, recent myocardial infarction or severe cardiac arrhythmia, immunocompromised status such as immunosuppressive therapy or a known disease of the immune system, previous enrolment in the present study, and previous intraabdominal chemotherapy or intraabdominal antibody therapy.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cisplatin and doxorubicin<br>Cisplatin and doxorubicin will be applied under pressure into the abdomen via laparoscopic trocars. The first 5 patients will receive doxorubicin 1.5 mg/m2 body surface in 50 ml NaCl 0,9% and cisplatin 7.5 mg/m2 in 50 ml NaCl 0,9% q 4 weeks for three courses. The next 5 patients will receive doxorubicin 2.25 mg/m2 body surface in 50 ml NaCl 0,9% and cisplatin 11.25 mg/m2 in 50 ml NaCl 0,9% q 4 weeks for three courses. The next 5 patients will receive doxorubicin 3 mg/m2 body surface in 50 ml NaCl 0,9% and cisplatin 15 mg/m2 in 50 ml NaCl 0,9% q 4 weeks for three courses. This schedule represents a three-step, 50% dose-escalation. Dose density will not be changed. | Drug: Cisplatin and doxorubicin<br>* The first 5 patients will receive doxorubicin 1.5 mg/m2 body surface in 50 ml NaCl 0,9% and cisplatin 7.5 mg/m2 in 50 ml NaCl 0,9% q 4 weeks for three courses. The next 5 patients will receive doxorubicin 2.25 mg/m2 body surface in 50 ml NaCl 0,9% and cisplatin 11.25 mg/m2 in 50 ml NaCl 0,9% q 4 weeks for three courses. The next 5 patients will receive doxorubicin 3 mg/m2 body surface in 50 ml NaCl 0,9% and cisplatin 15 mg/m2 in 50 ml NaCl 0,9% q 4 weeks for three courses. This schedule represents a three-step, 50% dose-escalation. Dose density will not be changed.<br>* Other names: Cisplatin TEVA, Doxorubicin 50 HEXAL®;Procedure: Cisplatin and doxorubicin<br>* intraperitoneal chemotherapy with cisplatin and doxorubicin in a dose-escalation scheme<br>* Other names: Intraperitoneal chemotherapy;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events according to CTCAE criteria |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical benefit according to RECIST criteria |  | 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ovarian cancer, recurrent, chemotherapy, intraperitoneal, cisplatin, doxorubicin