Analysis of renal function during angiostatic therapy with the COX-II inhibitor rofecoxib, in combination with pioglitazone, and trofosfamide or capecitabine in patients with metastatic / advanced cancer.
Organizational Data
- DRKS-ID:
- DRKS00000119
- Recruitment Status:
- Recruiting complete, study complete
- Date of registration in DRKS:
- 2009-06-22
- Last update in DRKS:
- 2010-07-14
- Registration type:
- Retrospective
Acronym/abbreviation of the study
No Entry
URL of the study
No Entry
Brief summary in lay language
Tumor growth is rendered possible by cell division and formation of new blood vessels, mediated in part by prostaglandins ? known as a messenger of inflammation. Rofecoxib inhibits the formation of prostaglandins and was in this study part of a (combined) tumorsuppressive regimen. Rofecoxib was well tolerated in this regimen, but withdrawn from the market because of an increased risk of myocardial infarction in the general population. We analysed renal function during therapy with Rofecoxib in a prospective trial of antiangiogenic / antiinflammatory therapy in patients with advanced cancer.
Brief summary in scientific language
Cyclooxygenases (both isoforms, COX-I and COX-II) oxidize arachidonic acid to prostaglandin H2, which is converted by different synthases to prostaglandin-E2, -D2, -I2, -F2alpha, and thromboxane A2. These different prostaglandins inhibit apoptosis and promote cell division, metastasis and angiogenesis leading to increased tumor growth. An antiangiogenic / antiinflammatory therapy with COX-II inhibitors and pioglitazone combined with metronomic low-dose chemotherapy with either capecitabine or trofosfamide seems to be well tolerated and promising in patients with advanced carcinomas. COX-II inhibitors have been shown to have less gastrointestinal side effects since they merely block COX-I which catalyzes the production of cytoprotective gastrointestinal prostaglandins. Rofecoxib however was associated with an increased risk of myocardial infarction and thus withdrawn from the market. In a (combined) tumorsuppressive regimen, rofecoxib was generally well tolerated. Since COX-II inhibitors are known to elicit renal side effects to a similar extent than conventional non-steroidal antiinflammatory drugs, the detailed analysis of renal function in a prospective trial of antiangiogenic / antiinflammatory therapy in advanced cancer seemed to be of interest.
Health condition or problem studied
- ICD10:
- C80 - Malignant neoplasm, without specification of site
- Healthy volunteers:
- No Entry
Interventions, Observational Groups
- Arm 1:
- Therapy with 25mg rofecoxib per day, 45mg pioglitazone per day and 1,0g capecitabine bid per os
- Arm 2:
- Therapy with 25mg rofecoxib per day, 45mg pioglitazone per day and 50mg trofosfamide per os
Endpoints
- Primary outcome:
- Primary Outcome / Outcome Measures (of the present secondary analysis):Assessment of renal function during and after end of treatment. Serum creatinine concentrations were measured before treatment and monthly during the treatment phase up to 6 months after end of treatment. Glomerular filtration rate was estimated using the method of Cockcroft and Gault.
- Secondary outcome:
- No Entry
Study Design
- Purpose:
- Other
- Allocation:
- N/A (single arm study)
- Control:
-
- Uncontrolled/single arm
- Phase:
- II
- Study type:
- Interventional
- Mechanism of allocation concealment:
- No Entry
- Blinding:
- No
- Assignment:
- Single (group)
- Sequence generation:
- No Entry
- Who is blinded:
- No Entry
Recruitment
- Recruitment Status:
- Recruiting complete, study complete
- Reason if recruiting stopped or withdrawn:
- No Entry
Recruitment Locations
- Recruitment countries:
-
- Germany
- Number of study centers:
- Monocenter study
- Recruitment location(s):
- No Entry
Recruitment period and number of participants
- Planned study start date:
- No Entry
- Actual study start date:
- 2000-07-26
- Planned study completion date:
- No Entry
- Actual Study Completion Date:
- 2005-10-04
- Target Sample Size:
- 87
- Final Sample Size:
- 87
Inclusion Criteria
- Sex:
- All
- Minimum Age:
- 18 Years
- Maximum Age:
- no maximum age
- Additional Inclusion Criteria:
- Patients with either gastrointestinal cancer, including pancreatic, and gall bladder cancer or urological cancer (group A) or metastatic melanoma, sarcoma, pulmonary and gynecological carcinoma or hematological malignancy (group B) were included in the. Additional eligibility criteria included: adequate baseline organ function as evidenced by a serum creatinine concentration at or below 1.8mg/dl, GOT, GPT and GGT below 1.25 times the normal concentration, white blood cell count over 2.0 cells per nL and a platelet count over 100000 cells per µL. Written informed consent had to be obtained before inclusion in the study.
Exclusion Criteria
Patients with significant comorbidity including acute infections, inadequately controlled diabetes mellitus, congestive heart failure, angina pectoris and cardiac arrhythmia requiring medical therapy were excluded from the study.
Addresses
Primary Sponsor
- Address:
- Abteilung für Hämatologie und Internistische Onkologie Klinikum der Universität RegensburgProf. Dr. med. Albrecht ReichleFranz-Josef-Strauß-Allee 1193053 RegensburgGermany
- Telephone:
- +49 941 944 5540
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
- Investigator Sponsored/Initiated Trial (IST/IIT):
- Yes
Contact for Scientific Queries
- Address:
- Abteilung für Hämatologie und Internistische Onkologie Klinikum der Universität RegensburgProf. Dr. med. Albrecht ReichleFranz-Josef-Strauß-Allee 1193053 RegensburgGermany
- Telephone:
- +49 941 944 5540
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Contact for Public Queries
- Address:
- Abteilung für Hämatologie und Internistische Onkologie Klinikum der Universität RegensburgProf. Dr. med. Albrecht ReichleFranz-Josef-Strauß-Allee 1193053 RegensburgGermany
- Telephone:
- +49 941 944 5540
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Sources of Monetary or Material Support
Institutional budget, no external funding (budget of sponsor/PI)
- Address:
- Klinikum der Universität RegensburgFranz-Josef-Strauß-Allee 1193053 RegensburgGermany
- Telephone:
- No Entry
- Fax:
- No Entry
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Ethics Committee
Address Ethics Committee
- Address:
- Ethikkommission der Universität RegensburgLandshuter Straße 493047 RegensburgGermany
- Telephone:
- +49-941-9435370
- Fax:
- +49-941-9435369
- Contact per E-Mail:
- Contact per E-Mail
- URL:
- No Entry
Vote of leading Ethics Committee
- Vote of leading Ethics Committee
- Date of ethics committee application:
- No Entry
- Ethics committee number:
- 00/149
- Vote of the Ethics Committee:
- Approved
- Date of the vote:
- 2000-10-04
Further identification numbers
- Other primary registry ID:
- No Entry
- EudraCT Number:
- No Entry
IPD - Individual Participant Data
- Do you plan to make participant-related data (IPD) available to other researchers in an anonymized form?:
- No Entry
- IPD Sharing Plan:
- No Entry
Study protocol and other study documents
- Study protocols:
- No Entry
- Study abstract:
- No Entry
- Other study documents:
- No Entry
- Background literature:
- No Entry
- Related DRKS studies:
- No Entry
Publication of study results
- Planned publication:
- No Entry
- Publikationen/Studienergebnisse:
- No Entry
- Date of first publication of study results:
- No Entry
- DRKS entry published for the first time with results:
- No Entry
Basic reporting
- Basic Reporting / Results tables:
- No Entry
- Brief summary of results:
- No Entry