- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02861872
Intra-peritoneal Chemotherapy in Ovarian Cancer
August 4, 2016 updated by: Radboud University Medical Center
Predictive Factors and Pharmacokinetics of Intra-peritoneal Chemotherapy
Ovarian cancer is the third most common gynecological malignancy worldwide.
Because of late, aspecific symptoms, the disease is usually diagnosed at an advanced stage.
Most patients experience recurrence and die as a result of the disease within 5 years.
Treatment is a combination of surgical debulking and systemic administered chemotherapy.
Intra-peritoneal (IP) chemotherapy with is currently considered the most effective treatment.
In patients with at least an optimal surgical debulking, this leads to an improvement in life expectancy from 50 to 66 months.
IP administration of chemotherapeutic agents is still not common practice.
Furthermore recent studies revealed that cancer cells express a variety of tumor antigens, which can be targeted by the immune system.
Also ovarian cancer shows evidence of a role for the immune system in clinical outcome.
Novel insights into the mechanism of action of chemotherapy indicate that the efficacy of chemotherapeutic interventions are dependent on the modulation of the immune system.
The impression exists that since IP chemotherapy is used, relatively more recurrences outside the abdominal cavity are observed.
As of yet, no studies have described pharmacokinetics and pharmacodynamics of IP administered cisplatin and paclitaxel in the blood circulation.
The investigators propose to study the use of this aspiration fluid from the IP cavity as a biomarker for the efficacy of chemotherapy intervention, monitor the effect of chemotherapy on IP tumor cells in the peritoneal cavity and monitor the effect of chemotherapy on immune cells present in the IP cavity.
As well the investigators propose to correlate the presence and amount of tumor cells in peritoneal fluid with the debulking efficacy and CA 125 levels.
Secondary to this the investigators intend to determine the pharmacokinetics of cisplatin and paclitaxel when administered in the IP cavity in the central circulation (plasma) as well as in the peritoneal fluid.
In this observational explorative study women, aged younger than 70 years, who will receive standard IP chemotherapy for advanced epithelial ovarian cancer, who are in an adequate physical and biochemical state to receive chemotherapy are included.
Immunological cell counts, tumor marker, immunological cell pathway activation and plasma concentrations of cisplatinum and paclitaxel in venous blood and in fluid aspirated from the abdominal cavity will be measured.
Study Overview
Status
Unknown
Study Type
Observational
Enrollment (Anticipated)
15
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Nijmegen, Netherlands, 6500HB
- Recruiting
- Radboudumc
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Contact:
- Mark Rietveld, M.D. MSc.
- Phone Number: +31243610353
- Email: mark.rietveld@radboudumc.nl
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Contact:
- Peter van Essen, MSc.
- Phone Number: +31243610353
- Email: peter.vanessen@radboudumc.nl
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Principal Investigator:
- Nelleke Ottevanger, M.D. PhD.
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Sampling Method
Non-Probability Sample
Study Population
Women, aged younger than 70 years, who will receive standard IP chemotherapy for advanced epithelial ovarian cancer, who are in an adequate physical and biochemical state to receive chemotherapy.
Description
Inclusion Criteria:
Patients receiving IP chemotherapy and therefore meeting the following criteria:
- Primary epithelial ovarian carcinoma FIGO stage III;
- Optimal or complete primary debulking (tumor rests ≤ 1cm;
- WHO 0 - 2;
- Adequate hematological function: WBC ≥ 3. 106/L en Platelets ≥ 100. 106/L,
- Adequate renal function (Creatinine clearance >60 ml/min (Cockcroft))
- Adequate liver function tests (bilirubin and/or transaminases <1.25 UNL)
Exclusion Criteria:
A potential subject who meets any of the following criteria will be excluded from participation in this study (according to the standard IP chemotherapy):
- Intestinal stoma proximal to the flexura lienalis;
- Postoperative sepsis after primary debulking;
- Haemoglobin < 6.0 mMol/L
- Extended intraperitoneal adhesions;
- Neurotoxicity grade>1;
- Previous chemotherapy for ovarian carcinoma;
- Symptomatic hearing loss;
- Age >70 years.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
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IP Patients
women, aged younger than 70 years, who will receive standard IP chemotherapy for advanced epithelial ovarian cancer, who are in an adequate physical and biochemical state to receive chemotherapy will be studied.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Primary immunological endpoint: study the use of aspiration fluid from the IP cavity as a biomarker for the efficacy of chemotherapy intervention, measured by decrease in tumor cell count in IP fluid.
Time Frame: Change in tumor cell counts between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Change in tumor cell counts between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Primary pharmacokinetic endpoint: study pharmacokinetics of cisplatin (platinum unbound fraction) when administered in the IP cavity in plasma and in the peritoneal fluid.
Time Frame: Change in platinum unbound fraction of cisplatin during the first course (first three weeks) of chemotherapy.
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Change in platinum unbound fraction of cisplatin during the first course (first three weeks) of chemotherapy.
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Primary pharmacokinetic endpoint: study pharmacokinetics of paclitaxel (plasma concentrations) when administered in the IP cavity in plasma and in the peritoneal fluid.
Time Frame: Change in plasma concentration of paclitaxel during the first course (first three weeks) of chemotherapy.
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Change in plasma concentration of paclitaxel during the first course (first three weeks) of chemotherapy.
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Secondary immunological endpoint: rise in dendritic cells
Time Frame: Change in dendritic cell counts between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Change in dendritic cell counts between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Secondary immunological endpoint: rise in tumor infiltrating lymphocytes
Time Frame: Change in lymphocyte cell counts between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Change in lymphocyte cell counts between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Secondary immunological endpoint: rise in natural killer cells
Time Frame: Change in natural killer cell counts between samples 15 min before and after administration of chemotherapy through completion of chemotherpy during 18 weeks
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Change in natural killer cell counts between samples 15 min before and after administration of chemotherapy through completion of chemotherpy during 18 weeks
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Secondary immunological endpoint: decrease in macrophages M1 type
Time Frame: Change in macrophages M1 type cell counts between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Change in macrophages M1 type cell counts between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Secondary immunological endpoint: decrease in macrophages M2 type
Time Frame: Change in macrophages M2 type cell counts between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Change in macrophages M2 type cell counts between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Secondary immunological endpoint: change in cytokine level (IL-6) measured by ELISA
Time Frame: Change in IL-6 cytokine levels between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Change in IL-6 cytokine levels between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Secondary immunological endpoint: change in cytokine level (IL-10) measured by ELISA
Time Frame: Change in IL-10 cytokine levels between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Change in IL-10 cytokine levels between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Secondary immunological endpoint: change in cytokine level (IFNg) measured by ELISA
Time Frame: Change in IFNg cytokine levels between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Change in IFNg cytokine levels between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Secondary immunological endpoint: change in cytokine level (TNFa) measured by ELISA
Time Frame: Change in TNFa cytokine levels between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Change in TNFa cytokine levels between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Secondary immunological endpoint: change in cytokine level (CCL2) measured by ELISA
Time Frame: Change in CCL2 cytokine levels between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Change in CCL2 cytokine levels between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Primary immunological endpoint: study the use of aspiration fluid from the IP cavity as a biomarker for the efficacy of chemotherapy intervention, measured by decrease in pSTAT in IP fluid.
Time Frame: Change in pSTAT between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Change in pSTAT between samples 15 min before and after administration of chemotherapy through completion of chemotherapy during 18 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Study Chair: Nelleke Ottevanger, M.D. PhD., Internist-oncologist and principal investigator
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Armstrong DK, Bundy B, Wenzel L, Huang HQ, Baergen R, Lele S, Copeland LJ, Walker JL, Burger RA; Gynecologic Oncology Group. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006 Jan 5;354(1):34-43. doi: 10.1056/NEJMoa052985.
- Tewari D, Java JJ, Salani R, Armstrong DK, Markman M, Herzog T, Monk BJ, Chan JK. Long-term survival advantage and prognostic factors associated with intraperitoneal chemotherapy treatment in advanced ovarian cancer: a gynecologic oncology group study. J Clin Oncol. 2015 May 1;33(13):1460-6. doi: 10.1200/JCO.2014.55.9898. Epub 2015 Mar 23. Erratum In: J Clin Oncol. 2015 Nov 1;33(31):3678.
- Schlappe BA, Mueller JJ, Zivanovic O, Gardner GJ, Long Roche K, Sonoda Y, Chi DS, O'Cearbhaill RE. Cited rationale for variance in the use of primary intraperitoneal chemotherapy following optimal cytoreduction for stage III ovarian carcinoma at a high intraperitoneal chemotherapy utilization center. Gynecol Oncol. 2016 Jul;142(1):13-18. doi: 10.1016/j.ygyno.2016.05.015. Epub 2016 May 21. Erratum In: Gynecol Oncol. 2016 Oct;143(1):225.
- Wright JD, Hou JY, Burke WM, Tergas AI, Chen L, Hu JC, Ananth CV, Neugut AI, Hershman DL. Utilization and Toxicity of Alternative Delivery Methods of Adjuvant Chemotherapy for Ovarian Cancer. Obstet Gynecol. 2016 Jun;127(6):985-991. doi: 10.1097/AOG.0000000000001436.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
July 1, 2016
Primary Completion (Anticipated)
December 1, 2017
Study Completion (Anticipated)
December 1, 2017
Study Registration Dates
First Submitted
July 20, 2016
First Submitted That Met QC Criteria
August 4, 2016
First Posted (Estimate)
August 10, 2016
Study Record Updates
Last Update Posted (Estimate)
August 10, 2016
Last Update Submitted That Met QC Criteria
August 4, 2016
Last Verified
July 1, 2016
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MOGYN16IP
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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