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

Ovarian Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02475772
• Other study ID #: PIPAC-OV2
• Secondary ID: 2014-001034-28
• Status: Completed
• Phase: Phase 1
• Start date: November 2016
• Est. completion date: May 2018

Study information

• Verified date: July 2022
• Source: Ruhr University of Bochum
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: May 2018
• Est. primary completion date: May 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. clinical and/or radiological evidence of PC,

2. 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,

3. blood and electrolyte counts, liver, and renal function parameters within 10% of the normal range established in the respective laboratory of the study institution,

4. provision of written informed consent, and

5. postmenopausal status.

Exclusion Criteria:

1. extraabdominal metastatic disease, with the exception of isolated pleural carcinomatosis/effusion,

2. chemotherapy or surgery within the last four weeks prior to the first PIPAC application,

3. previous treatment with maximum cumulative doses of doxorubicin, daunorubicin, epirubicin, idarubicin, and/or other anthracyclines and anthracenediones,

4. a history of allergic reaction to cisplatin or other platinum containing compounds or doxorubicin,

5. severe renal impairment, myelosuppression, severe hepatic impairment, severe myocardial insufficiency, recent myocardial infarction or severe cardiac arrhythmia,

6. immunocompromised status such as immunosuppressive therapy or a known disease of the immune system,

7. previous enrolment in the present study, and

8. previous intraabdominal chemotherapy or intraabdominal antibody therapy.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms
• Peritoneal Neoplasms

Intervention

Drug:
• Cisplatin and doxorubicin
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.

Procedure:
• Cisplatin and doxorubicin
intraperitoneal chemotherapy with cisplatin and doxorubicin in a dose-escalation scheme

Locations

Country	Name	City	State
Germany	Ruhr University Bochum, Germany, Marienhospital Herne	Herne	North-Rhine Westphalia

Sponsors (1)

Lead Sponsor	Collaborator
Clemens Tempfer

Country where clinical trial is conducted

Germany, 

References & Publications (2)

Tempfer CB, Celik I, Solass W, Buerkle B, Pabst UG, Zieren J, Strumberg D, Reymond MA. Activity of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) with cisplatin and doxorubicin in women with recurrent, platinum-resistant ovarian cancer: preliminary clinical experience. Gynecol Oncol. 2014 Feb;132(2):307-11. doi: 10.1016/j.ygyno.2013.11.022. Epub 2013 Nov 23. — View Citation

Tempfer CB, Giger-Pabst U, Seebacher V, Petersen M, Dogan A, Rezniczek GA. A phase I, single-arm, open-label, dose escalation study of intraperitoneal cisplatin and doxorubicin in patients with recurrent ovarian cancer and peritoneal carcinomatosis. Gynec — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Plasma concentrations of cisplatin and doxorubicin		12 weeks
Primary	Adverse events according to CTCAE criteria		12 weeks
Secondary	Clinical benefit according to RECIST criteria		12 weeks