Randomized Study of Docetaxel +/- ZD6474 in Metastatic TCC

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Massachusetts General Hospital
AstraZeneca
Information provided by (Responsible Party):
Toni Choueiri, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00880334
First received: April 10, 2009
Last updated: June 5, 2013
Last verified: June 2013
  Purpose

In this research study the investigators are looking to see if the combination of docetaxel plus Zactima 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. Zactima is a drug that is believed to stop new blood vessels from forming around cancer cells. The combination of docetaxel and Zactima 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 Zactima is better or worse then docetaxel alone.


Condition Intervention Phase
Transitional Cell Carcinoma
Urothelial Cancer
Drug: Docetaxel
Drug: Zactima
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Randomized Study of Docetaxel +/- ZD6474 in Metastatic TCC

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • To assess the efficacy of Zactima given in combination with docetaxel compared with the efficacy of docetaxel combined with placebo in this patient population. [ Time Frame: 4 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To study the tolerability and safety of Zactima given in combination with docetaxel compared with docetaxel combined with placebo in this patient population. [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 140
Study Start Date: September 2006
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Zactima & Docetaxel
Zactima orally and Docetaxel intravenously
Drug: Docetaxel
Given intravenously on Day 1 of each 21-day cycle
Other Name: Taxotere
Drug: Zactima
taken orally once a day, every day
Other Name: ZD6474
Active Comparator: Placebo and Docetaxel
Placebo orally and docetaxel intravenously
Drug: Docetaxel
Given intravenously on Day 1 of each 21-day cycle
Other Name: Taxotere
Drug: Placebo
Taken orally once a day every day

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 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 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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00880334

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Massachusetts General Hospital
AstraZeneca
Investigators
Principal Investigator: Toni Choueiri, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Toni Choueiri, MD, Assistant Professor of Medicine, Harvard Medical School, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00880334     History of Changes
Obsolete Identifiers: NCT00378794
Other Study ID Numbers: 06-116
Study First Received: April 10, 2009
Last Updated: June 5, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
TCC
Zactima
docetaxel
ZD6474
taxotere

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Docetaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014