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

NCT ID: NCT02475772

Last Updated: 2022-07-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2018-05-31

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.

Conditions

Ovarian Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cisplatin and doxorubicin

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.

Group Type: EXPERIMENTAL

Cisplatin and doxorubicin

Intervention Type: DRUG

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.

Cisplatin and doxorubicin

Intervention Type: PROCEDURE

intraperitoneal chemotherapy with cisplatin and doxorubicin in a dose-escalation scheme

Interventions

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.

Intervention Type: DRUG

Cisplatin and doxorubicin

intraperitoneal chemotherapy with cisplatin and doxorubicin in a dose-escalation scheme

Intervention Type: PROCEDURE

Other Intervention Names

Cisplatin TEVA, Doxorubicin 50 HEXAL®; Intraperitoneal chemotherapy

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Clemens Tempfer

OTHER

Sponsor Role: lead

Responsible Party

Clemens Tempfer

Chairman, Clinic Director

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Clemen^s B Tempfer, MD

Role: PRINCIPAL_INVESTIGATOR

Ruhr University Bochum

Locations

Ruhr University Bochum, Germany, Marienhospital Herne

Herne, North Rhine-Westphalia, Germany

Countries

Germany

References

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.

Reference Type: BACKGROUND

PMID: 24275155 (View on PubMed)

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. Gynecol Oncol. 2018 Jul;150(1):23-30. doi: 10.1016/j.ygyno.2018.05.001. Epub 2018 May 6.

Reference Type: RESULT

PMID: 29743140 (View on PubMed)

Other Identifiers

2014-001034-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PIPAC-OV2

Identifier Type: -

Identifier Source: org_study_id