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CompletedNCT02475772Updated Jul 8, 2022

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

A Phase 1 interventional study of Cisplatin and doxorubicin and Cisplatin and doxorubicin in Ovarian Cancer, sponsored by Clemens Tempfer. Completed at 1 site in Germany. Open to female participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2022-07-08.

Sponsored by Clemens Tempfer · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
15
Allocation
Not applicable
Ages
18 Years to 80 Years
Sex
Female
01

Study 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.

Read the 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.

02

Conditions studied

  • Ovarian Cancer

Keywords

  • ovarian cancer
  • recurrent
  • chemotherapy
  • intraperitoneal
  • cisplatin
  • doxorubicin
03

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
Female
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
15 participants (actual)

Study arms

  • Experimental
    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.

    Drug: Cisplatin and doxorubicin · Procedure: Cisplatin and doxorubicin

Interventions

  • DrugCisplatin 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.

    Also known as: Cisplatin TEVA, Doxorubicin 50 HEXAL®

  • ProcedureCisplatin and doxorubicin

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

    Also known as: Intraperitoneal chemotherapy

05

What researchers measure

Primary outcomes

  1. Adverse events according to CTCAE criteria

    Time frame: 12 weeks

Secondary outcomes

  1. Clinical benefit according to RECIST criteria

    Time frame: 12 weeks

Other outcomes

  1. Plasma concentrations of cisplatin and doxorubicin

    Time frame: 12 weeks

06

Study locations

1 site
  • Ruhr University Bochum, Germany, Marienhospital Herne
    Herne, North-Rhine Westphalia 44625, Germany
07

References and documents

Publications

  • 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. PubMed 24275155 ↗
  • 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. PubMed 29743140 ↗
08

Registry details

Key details

Study ID
NCT02475772
Lead sponsor
Clemens Tempfer
Responsible party
Clemens Tempfer (Chairman, Clinic Director, Ruhr University of Bochum) — Sponsor-investigator
First posted
Jun 19, 2015
Start date
Nov 2016
Primary completion
May 2018
Completion
May 2018
Last update
Jul 8, 2022

Study contacts

Clemen^s B Tempfer, MD
principal investigator · Ruhr University Bochum

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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