Individualizing Pazopanib therapy by exploRing the role of Early metabolic responsE and drug exposure as a preDICTor for treatment outcome in patients with STS

Phase 1

Conditions: soft tissue sarcoma patients
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2013-003533-16-NL

Lead Sponsor: Radboud University Nijmegen Medical Centre

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 30

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. Patients aged 66-69 are eligible for the imaging arm of the study, however they are excluded from the assessment of altered PK behavior in elderly.
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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1) Prior malignancy.
2) Central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously-treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants in prior 6 months time interval
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
6) History of one or more cardiovascular conditions within the past 6 months as unstable angina, myocardial infarction, etc.
7) Poorly controlled hypertension
8) History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
9) Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery).
10) Evidence of active bleeding or bleeding diathesis

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate whether early metabolic response is correlated to clinical benefit. And to evaluate the effect of age on pazopanib pharmacokinetcs.;Secondary Objective: To evaluate whether early metabolic response is correlated with pazopanib exposure. And to evaluate whether early metabolic response is correlated with the histological subtypes. ;Primary end point(s): The aim of the study is to show distinction between the PFS curves between the patients who have a more or less pronounced metabolic response. The second primary end point is to show a difference in pazopanib exposure between elderly compared to younger patients. ;Timepoint(s) of evaluation of this end point: On day 14 and 56 after start with pazopanib, pharmacokinetcs and metabolic response will be performed.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): To explore, quantify and describe the correlation between early metabolic response and pazopanib exposure on steady state pharmacokinetcs. 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. ;Timepoint(s) of evaluation of this end point: On day 14 and 56 after start with pazopanib, pharmacokinetcs and metabolic response will be performed.

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