Randomized Study of Docetaxel +/- Vandetanib in Metastatic TCC
Condition: Transitional Cell Carcinoma; Bladder Cancer
MeSH terms: Carcinoma, Transitional Cell
Intervention: Docetaxel; vandetanib; Placebo
Intervention description: Given intravenously on Day 1 of each 21-day cycle; taken orally once a day, every day; Taken orally once a day every day
Intervention MeSH terms: Docetaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 149.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: TCC; Zactima; docetaxel; ZD6474; taxotere

Summary:

      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.
    

Eligibility criteria:

        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.