The purpose of this study is to test the effect of the combination of sunitinib and
bortezomib. We will see what effects it has on your cancer and find the highest dose of each
agent that can be given without causing severe side effects.
This is a Phase I study assessing the combination of bortezomib and sunitinib in patients
with solid tumors that are refractory to standard chemotherapy.
The study will take place in two stages. In both stages, patients will receive sunitinib
orally with food once daily for 4 weeks and bortezomib by injection into a vein once a week
for 4 weeks. This will be followed by 2 weeks of rest. This 6-week period is called one
In stage 1, a maximum of 10 patients will be treated sequentially with increasing doses of
sunitinib (and a fixed dose of bortezomib). Each dose level must be well tolerated for the
next patient to start treatment at the next dose level. Whichever is the highest dose of
sunitinib that is well tolerated will then be used for the next stage.
In stage 2, a maximum of 20 patients will be treated sequentially with increasing doses of
bortezomib (and a fixed dose of sunitinib). Each dose level must be well tolerated for the
next patient to start treatment at the next dose level.
Together, the two stages will determine the highest doses of both sunitinib and bortezomib
that are well tolerated when given this combination. Determining these optimal doses is the
primary aim of this study. Patients will also be followed to see whether their tumor
responds to the treatment.
If a patient's cancer remains stable or improves, they can repeat the treatment cycles.
There is no defined end date to this study since patients will be followed for the duration
of their survival.
Each patient must meet all of the following inclusion criteria to be enrolled in the
- Refractory advanced solid tumor that has failed standard therapy.
- ECOG PS ≤ 2
- Voluntary written informed consent before performance of any study-related procedure
not part of normal medical care, with the understanding that consent may be withdrawn
by the subject at any time without prejudice to future medical care.
- Female subject is either post-menopausal or surgically sterilized or willing to use
an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine
device, diaphragm with spermicide, condom with spermicide, or abstinence) for the
duration of the study.
- Male subject agrees to use an acceptable method for contraception for the duration of
- Cardiac ejection fraction is more than 45%
- Patient has a platelet count of <100 x 109/L within 14 days before enrollment.
- Patient has an absolute neutrophil count of ANC <1.0 x 109/L within 14 days before
- Patient has a calculated or measured creatinine clearance of <30 mL/minute within 14
days before enrollment.
- AST, ALT, total bilirubin > twice the upper limits of normal.
- Received radiation to more than 30% of marrow volume
- Patient has greater than or equal to Grade 2 peripheral neuropathy within 14 days
- Myocardial infarction within 6 months prior to enrollment or has New York Heart
Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled
angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence
of acute ischemia or active conduction system abnormalities. Prior to study entry,
any ECG abnormality at Screening has to be documented by the investigator as not
- Patient has hypersensitivity to sunitinib, bortezomib, boron or mannitol.
- Uncontrolled hypertension
- History of venous thromboembolic events.
- Female subject is pregnant or breast-feeding. Confirmation that the subject is not
pregnant must be established by a negative serum Beta-human chorionic gonadotropin
(Beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not
required for post-menopausal or surgically sterilized women.
- Patient has received other investigational drugs with 14 days before enrollment
- Serious medical or psychiatric illness likely to interfere with participation in this
- Hemorrhagic tendency of the tumor