Randomized Study of Docetaxel +/- Vandetanib in Metastatic TCC

Randomized Study of Docetaxel +/- Vandetanib in Metastatic TCC

In this research study the investigators are looking to see if the combination of docetaxel plus Vandetanib is effective in the treatment of metastatic transitional cell carcinoma (TCC). Docetaxel is a chemotherapy drug that kills cancer cells that are dividing. It is widely used in TCC. Vandetanib is a drug that is believed to stop new blood vessels from forming around cancer cells. The combination of docetaxel and Vandetanib has been studied in people with lung cancer and found to be helpful in killing cancer cells. Thus, this study is looking at people with TCC, to see if the combination of docetaxel plus Vandetanib is better or worse then docetaxel alone.

• Because no one knows which of the study options is best, and all of the options are considered equally likely to work, participants will be randomized into one of two study groups: docetaxel plus Vandetanib or docetaxel plus placebo.
• Each treatment cycle lasts three weeks during which time the participant will be taking Vandetanib or placebo once a day, every day. On Day 1 of each cycle (a cycle is 21 days), participants will receive docetaxel as an infusion through a vein in the arm over one hour.
• On Day 1 of every cycle the following tests and procedures will be performed: physical exam and blood tests. On day 1 and on Day 8 of the first cycle only, participants will have an ECG. Every 6-9 weeks (every 2 to 3 cycles), the participants tumor will be assessed by x-ray, CT scan, bone scan, and/or MRI.

Inclusion Criteria:

• Histologically or cytologically confirmed TCC. Mixed histologies are allowed as long as the predominant histology is TCC.
• Must have received chemotherapy treatment for TCC and have stage IV TCC at the time of study entry. 1-3 prior systemic chemotherapeutic or investigational treatment regimens for TCC are allowed. Patient with more regimens than the ones allowed may be included at the discretion of the Overall Principal Investigator if it is felt that the regimen has shown minimal activity and toxicity and will not influence prior or subsequent therapies. Specifically, participants must meet one or more of the following criteria: a) Progression after treatment with a regimen that includes a platinum salt (e.g. carboplatin or cisplatin) for Stage IV disease OR b) Disease recurrence within two years (from the date of last dose of chemotherapy or surgery until day the informed consent is signed) after neoadjuvant or adjuvant treatment with a regimen that includes a platinum salt.
• Measurable or evaluable disease, as defined by RECIST. If all sites of measurable or evaluable disease have been irradiated, one site must have demonstrated growth after irradiation.
• Adequate contraceptive method for subjects with reproductive potential (females with reproductive potential must have a negative serum pregnancy test within 7 days of study entry).
• ECOG PS 0 or 1
• 18 years of age or older

Exclusion Criteria:

• History of treatment of TCC (in any setting-neoadjuvant, adjuvant or for metastatic disease) with docetaxel. Patients treated with prior paclitaxel (Taxol) are eligible.
• History of treatment with a VEGF-axis active agent, including antibodies to VEGF, antibodies to VEGF receptors, or VEGF receptor tyrosine kinase inhibitors.
• Laboratory results as outlined in the protocol
• Evidence of uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol
• Clinically significant cardiac event such as myocardial infarction; NHYA classification of heart disease >2 within three months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia
• History of arrhythmia, 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.
• Previous history of QTc prolongation as a result from other medication that required discontinuation of that medication.
• Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age.
• Presence of left bundle branch block (LBBB)
• QTc with Bazett's correction that is unmeasurable, or 480 msec or greater on screening ECG. If a subject has a QTc of 480msec or greater 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 <480 msec in order for the subject to be eligible for the study.
• Any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes or induce CYP3A4 function.
• Hypertension not controlled by medical therapy
• Currently active diarrhea
• Women who are currently pregnant or breast feeding
• Receipt of any investigational agent, chemotherapy or radiation therapy within 21 days prior to Study Day 1
• Any unresolved non-hematologic toxicity greater than CTCAE grade 1 from previous anti-cancer therapy (other than alopecia).
• Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy.
• Grade 2 or greater peripheral neuropathy
• Previous or current malignancies within the last 3 years, with the exception of in situ carcinoma of the cervix, adequately treated carcinoma of the skin, small renal masses, and adequately treated localized prostate cancer. Other cancers that are highly likely to be cured (cure rate of 75% or greater) may be included at the discretion of the Overall Principal Investigator.
• History of severe hypersensitivity reaction to drugs formulated with polysorbate 80.