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Randomized Study of Docetaxel +/- ZD6474 in Metastatic TCC

Phase 2
18 Years
Open (Enrolling)
Transitional Cell Carcinoma, Urothelial Cancer

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Trial Information

Randomized Study of Docetaxel +/- ZD6474 in Metastatic TCC

- 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 Zactima or docetaxel plus placebo.

- Each treatment cycle lasts three weeks during which time the participant will be taking
Zactima 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

- 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

- 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

- 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.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

To assess the efficacy of Zactima given in combination with docetaxel compared with the efficacy of docetaxel combined with placebo in this patient population.

Outcome Time Frame:

4 years

Safety Issue:


Principal Investigator

Toni Choueiri, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

September 2006

Completion Date:

December 2013

Related Keywords:

  • Transitional Cell Carcinoma
  • Urothelial Cancer
  • TCC
  • Zactima
  • docetaxel
  • ZD6474
  • taxotere
  • Carcinoma
  • Carcinoma, Transitional Cell



Beth Israel Deaconess Medical Center Boston, Massachusetts  02215
Dana-Farber Cancer Institute Boston, Massachusetts  02115
Massachusetts General Hospital Boston, Massachusetts  02114-2617