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A phase I study of the combination of daily oral pazopanib with intravenous ifosfamide in patients with advanced solid malignancies.


- candidate number6615
- NTR NumberNTR2063
- ISRCTNISRCTN wordt niet meer aangevraagd.
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR16-okt-2009
- Secondary IDs2008-245 EMC
- Public TitleA phase I study of the combination of daily oral pazopanib with intravenous ifosfamide in patients with advanced solid malignancies.
- Scientific TitleA phase I study of the combination of daily oral pazopanib with intravenous ifosfamide in patients with advanced solid malignancies.
- ACRONYMPazi
- hypothesisTo determine the MTD of pazopanib in combination with standard doses of ifosfamide, dosed according to two regimens (continuous ifosfamide infusion [Arm A]; short ifosfamide infusion [Arm B]), in subjects with solid malignancies.
- Healt Condition(s) or Problem(s) studiedSarcoma, Advanced solid malignancy
- Inclusion criteria1. Subjects must provide written informed consent prior to performance of study specific procedures or assessments, and must be willing to comply with treatment and follow up assessments and procedures;
2. Histologically or cytologically confirmed diagnosis of advanced solid tumor for which ifosfamide-based systemic therapy is considered appropriate or for which there is no standard therapy;
3. Age >18 years;
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
5. Adequate organ function;
6. There must be measurable disease or evaluable disease (according to RECIST v1.1 criteria) for subjects to be included in the cohort expansion phase. Measurable disease is not a criterion for subjects enrolling in the dose escalation phase;
7. Able to swallow and retain oral medication;
8. A life expectancy of at least 12 weeks.
- Exclusion criteria1. Unable to discontinue prohibited medications, as listed in Section 5.5.2, 14 days or five half-lives (whichever is longer) of the drug prior to Visit 1 and for the duration of the study;
2. Clinically significant gastrointestinal abnormalities which might interfere with oral dosing;
3. Any unstable or serious concurrent condition (e.g., active infection requiring systemic therapy);
4. Poorly controlled hypertension (SBP of 160 mmHg, or DBP of 90 mmHg). Note: Initiation or adjustment of blood pressure medication is permitted prior to study entry provided the subject has 2 consecutive blood pressure readings less than 160/90 mmHg, each separated by a minimum of 1 hour. These readings need to be collected prior to the first dose. See Appendix 2 for details on blood pressure control and reassessment prior to study enrollment;
5. Prolongation of corrected QT interval (QTc) >480 msecs;
6. History of any one of more of the following cardiovascular conditions within the past 6 months:
A. Cardiac angioplasty or stenting;
B. Myocardial infarction;
C. Unstable angina;
D. Symptomatic peripheral vascular disease;
E. Class II, III or IV congestive heart failure as defined by the New York Heart Association (NYHA).
7. History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulant agents (excluding therapeutic warfarin) for at least 6 weeks are eligible;
8. Macroscopic hematuria;
9. Hemoptysis that is clinically relevant within 4 weeks of first dose of study drug;
10. Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer;
11. Chemotherapy or radiation therapy within 2 weeks prior to the first dose of study drug;
12. Biological therapy, hormonal therapy or treatment with an investigational agent within 28 days (for bevacizumab, 60 days) prior to the first dose of study drug;
13. Has not recovered from toxicities associated with prior anti-cancer therapy;
14. Metastatic disease to the brain or leptomeninges (of note: radiologic assessment of the brain is only needed in those subjects with clinical symptoms suspicious for brain metastases);
15. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol;
16. Clinically assessed as having inadequate venous access for PK sampling;
17. Is pregnant or lactating. Note: Female subjects who are lactating should discontinue nursing prior to the first dose of study drug and should refrain from nursing throughout the treatment period and for 14 days following the last dose of study drug.
- mec approval receivedyes
- multicenter trialyes
- randomisedno
- groupParallel
- Type2 or more arms, non-randomized
- Studytypeintervention
- planned startdate 10-jun-2009
- planned closingdate7-jan-2011
- Target number of participants80
- InterventionsCombination therapy will consist out of daily pazopanib and 3-weekly infusion of ifosfamide. Up to 6 courses of ifosfamide will be administered.
- Primary outcomeTo determine the MTD of pazopanib in combination with standard doses of ifosfamide, dosed according to two regimens (continuous ifosfamide infusion [Arm A]; short ifosfamide infusion [Arm B]), in subjects with solid malignancies.
- Secondary outcome1. To assess the safety and tolerability of the investigational combination of pazopanib and ifosfamide;
2. To characterize the PK of pazopanib when administered alone and with ifosfamide, and of ifosfamide and its metabolites when administered alone and with pazopanib (with continuous and short ifosfamide regimens);
3. To analyze biomarkers in blood associated with clinical outcome to treatment to allow identification of markers useful for selecting subjects likely to benefit from therapy;
4. To explore the anti-tumor activity of the combination of pazopanib and ifosfamide (continuous and short ifosfamide regimens) in solid tumors.
- TimepointsAdverse event observation during first or first 2 cycles.
- Trial web siteN/A
- statusopen: patient inclusion
- CONTACT FOR PUBLIC QUERIESProf. Dr. S. Sleijfer
- CONTACT for SCIENTIFIC QUERIESProf. Dr. S. Sleijfer
- Sponsor/Initiator Erasmus Medical Center
- Funding
(Source(s) of Monetary or Material Support)
GlaxoSmithKline
- PublicationsN/A
- Brief summaryThis is a dose-finding (phase I) study on the combination of pazopanib and ifosfamide. Ifosfamide (standard dose) will be combined with escalating doses of pazopanib. No intrapatient escalation will take place. The highest dosing combination with as Dose-limiting toxicity occurring in less then 1/3 of patients in the first treatment cycle will be the maximally tolerated dose. Potential drug-drug interaction will be studied bij pharmacokinetic analysis. Efficacy will be routinely assessed by CT-scan.
- Main changes (audit trail)
- RECORD16-okt-2009 - 26-okt-2009


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