This study uses the drugs Abraxane (also called ABI-007) and Vandetanib (also called Zactima
and ZD6474). Abraxane has been approved by the Food and Drug Administration (FDA), for the
treatment of breast cancer. Vandetanib is an experimental drug and has not been approved by
the FDA for the treatment of any condition. Vandetanib has shrunk some non-small cell lung
cancer, prostate cancer and thyroid cancer in some studies in humans. This combination of
drugs is not approved for the treatment of any condition by the FDA.
This study is being done in two phases. The first phase of the trial has two main
objectives: 1) To find the highest daily dose of vandetanib that can be given safely with
once weekly Abraxane and 2) To find the highest daily dose of vandetanib that can be given
safely with Abraxane given every three weeks. Participants will be randomly assigned (like
flipping a coin) to receive Abraxane weekly (Arm A) or once every three weeks (Arm B). The
dose of Abraxane given will remain the same for the whole study - 100 mg/m2 when given
weekly and 260 mg/m2 when given every three weeks. Participants will be entered onto each
arm of the study in groups of three, and higher doses of vandetanib will be given each group
of participants. The increase of vandetanib will stop once more than one participant has
serious side effects. The highest dose of vandetanib that can be given with Abraxane
(without serious side effects) in each Arm will be called the pilot dose.
In the second phase of the study twenty participants will be randomly assigned to Arm A or
Arm B and receive the pilot dose of vandetanib that was reached in the first phase of the
study. The purpose of the second phase of the study is to see how many tumors shrink when
participants receive the pilot dose of the drug combination on each Arm, as well as to
gather more information about the side effects.
- SWOG performance status of 0-2
- Projected life expectancy of at least 3 months
- Female and or male age 18 years and over
- Provision of informed consent prior to any study-related procedures.
- Patients must not have history of torsades de pointes ventricular arrythmia
- Patients must not have a prolonged QT interval > 450 msec on baseline EKG in the
presence of normal serum and magnesium values. Patients with QTc with Bazett's
correction that is unmeasurable are ineligible. (Note: If a subject has a QTc
interval less than or equal to 450 msec on screening ECG, the screen ECG may be
repeated twice (at least 24 hours apart). The average QTc from the three screening
ECGs must be <450 msec in order for the subject to be eligible for the study.)
Patients who are receiving a drug that has a risk of QTc prolongation are excluded
if QTc is ≥ 460 msec.
- Female patients must not be pregnant due to the potential mutagenicity and
teratogenicity of this treatment. A pregnancy test must be administered 7 days prior
to administration of therapy to women of childbearing potential.
- Patients must agree to use some form of contraception while on this study at
initiation and for the duration of participation in the study. Sexually active males
must also use a reliable and appropriate method of contraception. Post-menopausal
women must be amenorrheic for at least 12 months to be considered of non-childbearing
- Patients must have recovered from acute toxicities from previous surgery,
chemotherapy or radiation therapy
- Adequate organ function defined as:
ANC > 1500/mm3 Platelet count > 100,000 cells/mm3 Hemoglobin > 9.0g/dL Serum creatinine <
1.5 mg/dl or creatinine clearance > 50 mL/minute Hepatic function: Patients must have
adequate liver functions: AST or ALT < 2.5 X upper limit of normal (ULN), alkaline
phosphatase < 2.5 X upper limit of normal. In patients with bone metastasis and no
evidence of liver metastasis and bilirubin < upper limit of normal an alkaline phosphatase
< 5 ULN will be allowed.
In patients with known liver involvement: AST or ALT and alkaline phosphatase < 5 ULN,
Serum Bilirubin < 1.5 mg/dL
- Peripheral neuropathy grade 0-1
- No other concomitant therapy directed at the cancer is allowed. All prior therapy
must have been completed > 4 weeks prior to study enrollment.
- Patients diagnosed with advanced prostate cancer must have progressed on or have been
intolerant of a docetaxel based regimen.
- Laboratory results:
- Serum bilirubin > 1.5 the upper limit of reference range (ULRR)
- Serum creatinine >1.5 x ULRR or creatinine clearance < 50 mL/minute (calculated
by Cockcroft-Gault formula.)
- Potassium, < 4.0 mmol/L despite supplementation; serum calcium (ionized or
adjusted for albumin,) or magnesium out of normal range despite supplementation
- Evidence of severe or uncontrolled systemic disease or any concurrent condition
which in the Investigator's opinion makes it undesirable for the patient to
participate in the trial or which would jeopardize compliance with the protocol.
- Clinically significant cardiovascular event (e.g. myocardial infarction,
superior vena cava syndrome (SVC), New York Heart Association (NYHA)
classification of heart disease >2 (see Appendix B) within 3 months before
entry; or presence of cardiac disease that, in the opinion of the Investigator,
increases the risk of ventricular arrhythmia.
- History of arrhythmia (multifocal premature ventricular contractions (PVCs),
bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial
fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or
asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled
on medication is not excluded.
- QTc prolongation with other medications that required discontinuation of that
- Congenital long QT syndrome,or 1st degree relative with unexplained sudden death
under 40 years of age.
- Presence of left bundle branch block (LBBB.)
- Any concurrent medication that may cause QTc prolongation or induce Torsades de
Pointes ( Protocol Appendix A lists relevant medications that have a risk of
Torsades de Pointes or QTc prolongation.) Drugs listed in Appendix A, Table 2,
that in the investigator's opinion cannot be discontinued, are allowed however,
must be monitored closely (please see section 4.2).
- Hypertension not controlled by medical therapy (systolic blood pressure greater
than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg)
- Currently active diarrhea that may affect the ability of the patient to absorb
the Vandetanib or tolerate diarrhea.
- Women who are currently pregnant or breast feeding.
- Receipt of any investigational agents within 30 days prior to commencing study
- Last dose of prior chemotherapy discontinued less than 4 weeks before the start
of study therapy
- Last radiation therapy within the last 4 weeks before the start of study
therapy, except palliative radiotherapy
- Any unresolved toxicity greater than CTC grade 1 from previous anti-cancer
- Major surgery within 4 weeks or incompletely healed surgical incision before
starting study therapy.
- Previous enrollment in the current study.
- Patients with the following conditions: Colon cancer, Rectal cancer