Ausschlusskriterien
1. Prior malignancy
• Note: Subjects who have had another malignancy and have been disease-free
for 5 years, or subjects with a history of completely resected nonmelanomatous
skin carcinoma or successfully treated in situ carcinoma are
eligible.
2. Patient has received prior treatment with any anti-angiogenic agent including
bevacizumab and tyrosine kinase inhibitors
3. Active malignancy or any malignancy in the last 5 years prior to first dose of study drug
other than LMS and CS
4. History or clinical evidence of central nervous system (CNS) or leptomeningeal
metastases, except for individuals who have previously-treated CNS metastases, are
asymptomatic, and have had no requirement for steroids or anti-seizure medication for
6 months prior to first dose of study drug. Screening with CNS imaging studies
(computed tomography [CT] or magnetic resonance imaging [MRI]) is required only if
clinically indicated or if the subject has a history of CNS metastases
5. Clinically significant gastrointestinal abnormalities that may increase the risk for
gastrointestinal bleeding including, but not limited to:
• Active peptic ulcer disease
• Known intraluminal metastatic lesion/s with risk of bleeding
• Inflammatory bowel disease (e.g. ulcerative colitis, Crohn’s disease), or other
gastrointestinal conditions with increased risk of perforation
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 28 days prior to beginning study treatment
• Grade 3/4 diarrhea
6. Corrected QT interval (QTc) > 450 msecs using Barzett’s formula
7. History of any one or more of the following cardiovascular conditions within the past 6
months:
• Cardiac angioplasty or stenting
• Myocardial infarction
• Unstable angina
• Coronary artery bypass graft surgery
• Symptomatic peripheral vascular disease
• Class III or IV congestive heart failure, as defined by the New York Heart
Association (NYHA)
• Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140
mmHg or diastolic blood pressure (DBP) of ≥ 90 mmHg].
Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior
to study entry. BP must be re-assessed on two occasions that are separated by a
minimum of 1 hour; on each of these occasions, the mean (of 3 readings) SBP /
DBP values from each BP assessment must be <140/90 mmHg in order for a
subject to be eligible for the study (refer to study protocol for details on BP control
and re-assessment prior to study enrollment)
8. History of cerebrovascular accident including transient ischemic attack (TIA),
pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6
months.
• Note: Subjects with recent DVT who have been treated with therapeutic anticoagulating
agents for at least 6 weeks are eligible
9. Major surgery or trauma within 28 days prior to study enrolment or any non- healing
wound, fracture or ulcer (procedures such as catheter placement not considered to
be major)
10. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to Pazopanib or Gemcitabine
11. Evidence of active bleeding or bleeding diathesis
12. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
13. Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks prior to the first
dose of study drug
14. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that
could interfere with subject’s safety, provision of informed consent, or compliance to
study procedures
15. Unable or unwilling to discontinue use of prohibited medications listed in the study
protocol for at least 14 days or five half-lives of a drug (whichever is longer) prior to
the first dose of study drug and for the duration of the study
16. Treatment with any of the following anti-cancer therapies
- Radiation therapy, surgery or tumour embolization within 14 days prior to the first
dose of study drug
- Chemotherapy, immunotherapy, biologic therapy, investigational therapy or
hormonal therapy within 14 days or five half-lives of a drug (whichever is longer)
prior to the first dose of study drug
17. Any ongoing toxicity from prior anti-cancer therapy that is >Grade 1 and/or that is
progressing in severity, except alopecia
18. Pregnancy (for women of childbearing potential to be confirmed by negative serum
pregnancy test) or lactation period
Women of childbearing potential:
missing contraception (Pearl-Index <1, e.g. hormonal contraception including the
combined oral contraceptive pill, the transdermal patch, and the contraceptive
vaginal ring, intrauterine devices or sterilization) for 14 days before exposure to
investigational product, during study treatment and for at least 21 days after the last
dose of investigational product.
19. Medical or psychological conditions that would not permit the subject to complete the
study or sign informed consent
20. Legal incapacity or limited legal capacity
21. Participation in another clinical study with experimental therapy within 30 days prior to study enrolment