Randomized Study of Docetaxel +/- Vandetanib in Metastatic TCC

NCT00880334 | Completed Phase 2 Results DMC

• 1 other identifier: 06-116
• Study Type: interventional
• Target: 149
• Locations: 1 country
• Sites: 3

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.

Conditions

Transitional Cell Carcinoma; Bladder Cancer

Keywords

TCC; Zactima; docetaxel; ZD6474; taxotere

Outcome Measures

Primary Outcomes (1)

• Median Progression-Free Survival (PFS)

  PFS based on the Kaplan-Meier method is defined as the time between randomization and documented disease progression (PD) per RECIST 1.0 criteria or death, or is censored at time of last disease assessment. Per RECIST 1.0 for target lesions, PD is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or appearance of new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

  Disease evaluations occurred at week 6 and 12 and thereafter every 3 cycles/9 weeks on treatment and every 3 months in follow-up. Participants were followed until PD, death or lost to follow-up. Median survival follow-up was 12 months (range 1-26).

Secondary Outcomes (3)

• Grade 3-5 Toxicity Rate

  Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort approximated 2 cycles (range 1-31).

• Median Overall Survival

  Off treatment, patients were followed for survival information every 6 months (±1 month) until death,up to 2 years after discontinuing therapy, or until lost to follow-up. Median survival follow-up for the study cohort was 12 months (95% CI: 9-18 months).

• Objective Response Rate

  Disease evaluations occurred at week 6 and 12 and thereafter every 3 cycles/9 weeks on treatment. Median treatment duration for this study cohort approximated 2 cycles (range 1-31).

Study Arms (2)

vandetanib & Docetaxel

EXPERIMENTAL

vandetanib orally and Docetaxel intravenously

Drug: Docetaxel; Drug: vandetanib

Placebo and Docetaxel

ACTIVE COMPARATOR

Placebo orally and docetaxel intravenously

Drug: Docetaxel; Drug: Placebo

Interventions

Docetaxel DRUG

Given intravenously on Day 1 of each 21-day cycle

Also known as: Taxotere

Placebo and Docetaxel; vandetanib & Docetaxel

vandetanib DRUG

taken orally once a day, every day

Also known as: ZD6474, Zactima

vandetanib & Docetaxel

Placebo DRUG

Taken orally once a day every day

Placebo and Docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• years of age or older

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Brigham and Women's Hospital: collaborator
• Beth Israel Deaconess Medical Center: collaborator
• Massachusetts General Hospital: collaborator
• AstraZeneca: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Choueiri TK, Ross RW, Jacobus S, Vaishampayan U, Yu EY, Quinn DI, Hahn NM, Hutson TE, Sonpavde G, Morrissey SC, Buckle GC, Kim WY, Petrylak DP, Ryan CW, Eisenberger MA, Mortazavi A, Bubley GJ, Taplin ME, Rosenberg JE, Kantoff PW. Double-blind, randomized trial of docetaxel plus vandetanib versus docetaxel plus placebo in platinum-pretreated metastatic urothelial cancer. J Clin Oncol. 2012 Feb 10;30(5):507-12. doi: 10.1200/JCO.2011.37.7002. Epub 2011 Dec 19.

  PMID: 22184381 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Urinary Bladder Neoplasms

Interventions

Docetaxel; vandetanib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Toni Choueiri, MD
• Organization: Dana-Farber Cancer Institute

toni_choueiri@dfci.harvard/edu

617-632-5456

Study Officials

• Toni Choueiri, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine, Harvard Medical School

Study Record Dates

• First Submitted: April 10, 2009
• First Posted: April 13, 2009
• Study Start: September 1, 2006
• Primary Completion: December 1, 2013
• Study Completion: May 1, 2015
• Last Updated: September 18, 2018
• Results First Posted: June 4, 2014

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)