Brief Title
Randomized Study of Docetaxel +/- Vandetanib in Metastatic TCC
Official Title
Randomized Study of Docetaxel +/- Vandetanib in Metastatic TCC
Brief 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.
Detailed Description
- 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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Median Progression-Free Survival (PFS)
Secondary Outcome
Grade 3-5 Toxicity Rate
Condition
Transitional Cell Carcinoma
Intervention
Docetaxel
Study Arms / Comparison Groups
vandetanib & Docetaxel
Description: vandetanib orally and Docetaxel intravenously
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
149
Start Date
September 2006
Completion Date
May 2015
Primary Completion Date
December 2013
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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Toni Choueiri, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00880334
Organization ID
06-116
Responsible Party
Principal Investigator
Study Sponsor
Dana-Farber Cancer Institute
Collaborators
Brigham and Women's Hospital
Study Sponsor
Toni Choueiri, MD, Principal Investigator, Dana-Farber Cancer Institute
Verification Date
August 2018