Primary Objectives:- To evaluate whether early metabolic response is correlated to clinical benefit (defined as PFS).- To evaluate the effect of age (>= 70 years) on pazopanib pharmacokinetics (AUC0-24hr).Secondary Objectives:- To evaluate…
ID
Source
Brief title
Condition
- Soft tissue neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- The aim of this study is to show distinction between the PFS curves between
the patients who have a more or less pronounced metabolic response.
- The aim of this study is to show a difference in pazopanib exposure
(AUC0-24hr) between elderly (>= 70 years) compared to younger (<= 65 years)
patients. The difference in exposure should at least be 15% to consider
expansion of the study to a larger cohort.
Secondary outcome
- To explore, quantify and describe the correlation between early metabolic
response and pazopanib exposure (AUC) on steady-state pharmacokinetics
- To explore, quantify and describe the correlation between tumor histology and
early metabolic response
- To explore, quantify and describe the correlation between pazopanib exposure
and the frequency of adverse events as graded by CTCAE v4.0
Background summary
The ability to target mutated oncogenes has led to significant therapeutic
advance in oncology. Recently, based on the outcome of the PALETTE-study, the
FDA approved pazopanib for the treatment of patients with non-adipocytic
soft-tissue sarcoma. However, with these new targeted therapies new problems
arise. Reliable imaging to observe early response is required to minimize
unnecessary toxicity and to avoid underestimations of initial responses as
traditional methods like radiological responses has a large delay between
treatment onset and evaluation of treatment benefit. FDG-PET imaging after a
single cycle of neoadjuvant therapy appeared to be predictive for survival in
patients with high-grade soft tissue sarcomas. Absolutely no information is
available on the diagnostic value of FDG-PET in patients with Soft Tissue
Sarcoma (STS) treated with pazopanib. In the proposed study we would therefore
like to investigate what the relation is between: 1. tumor histology, 2.
metabolic response (FDG-PET), 3. pazopanib exposure(AUC0-24hr) and 4. clinical
benefit in patients with STS who are treated with pazopanib. This approach
could facilitate future early clinical decision making (dose personalization /
altering therapy) in patients with soft tissue sarcoma.
With an increasing number of elderly patients with cancer the geriatric
patients will be encountered frequently in the clinical practice. However
little information is available whether and how the dose of pazopanib should be
adjusted in this substantial subgroup of patients, while it is evident that
multiple factors influencing pazopanib pharmacokinetics (PK) are altered with
increased age: the absorption is decreased due to reduced gastric acid
secretion, reduced gastrointestinal motility, reduced splanchnic blood flow and
potentially loss of absorption surface. The volume of distribution is altered
due to decreased plasma albumin content and decreased total body water with
increased fat content. Finally, the hepatic metabolism is changed due to
decreased concentration and activity of cytochrome P450 enzymes. Therefore we
would like to study pazopanib pharmacokinetics in the elderly patient.
Study objective
Primary Objectives:
- To evaluate whether early metabolic response is correlated to clinical
benefit (defined as PFS).
- To evaluate the effect of age (>= 70 years) on pazopanib pharmacokinetics
(AUC0-24hr).
Secondary Objectives:
- To evaluate whether early metabolic response (% decrease in FDG uptake
(SUVmax) due to pazopanib therapy) is correlated with pazopanib exposure
(AUC0-24hr)
- To evaluate whether early metabolic response (% decrease in FDG uptake
(SUVmax) due to pazopanib therapy) is correlated with the histological
subtypes.
Study design
Phase IV post registration prospective observational feasibility study in
patients with metastatic STS.
Study burden and risks
Patients have to fill in a diary during the 8 weeks of the study, in which they
have to record their time of taking their medication. Patients will spend two
days in the hospital where blood will be taken at nine different time points
from a peripheral vein. Patients will get 3 PETscans, where they will receive a
dose of FDG. The total radiation dose is weight dependent, but is estimated at
4 millisievert (mSv) per PET, resulting in 12 mSv cumulatively.
Geert Grooteplein 10
Nijmegen 6525 GA
NL
Geert Grooteplein 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
1) 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.
2) Age >= 18 years or legal age of consent if greater than 18 years.
3) Histological confirmed diagnosis of selective subtypes of advanced soft tissue sarcoma (STS) who have received prior chemotherapy for metastatic disease or who have progressed within 12 months after (neo) adjuvant therapy.
4) Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
5) Measurable disease criteria (RECIST 1.1).
6) No radio-, chemo- or tumor specific targeted therapy within the last 4 weeks prior to study entry.
7) Adequate organ system function.
8) Minimal evaluable laesion of >= 15mm.
Exclusion criteria
1) Prior malignancy.
2) Central nervous system (CNS) metastases at baseline
3) Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding
4) Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product
5) Corrected QT interval (QTc) > 480msecs
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-003533-16-NL |
| CCMO | NL46119.091.13 |