Transitional Cell CarcinomaPhase 2NCT00880334
Randomized Study of Docetaxel +/- Vandetanib in Metastatic TCC
A Phase 2 study testing Docetaxel and vandetanib in people with Transitional Cell Carcinoma and Bladder Cancer, run by Dana-Farber Cancer Institute at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Transitional Cell Carcinoma, Bladder Cancer
- What is being tested?
- Docetaxel and vandetanib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 149 participants
- Where
- 3 sitesUnited States
- Study dates
- Sep 2006to May 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
About this study
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.
Read the 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.
- Conditions
- Transitional Cell Carcinoma, Bladder Cancer
- Being tested
- Docetaxel, vandetanib, Placebo
- Keywords
- TCC, Zactima, docetaxel, ZD6474, taxotere
- Medical subject headings
- Carcinoma, Transitional Cell, Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DocetaxelDrug
Also called Taxotere
Given intravenously on Day 1 of each 21-day cycle
vandetanibDrug
Also called ZD6474, Zactima
taken orally once a day, every day
PlaceboDrug
Taken orally once a day every day
| Study group | Role | What they receive |
|---|---|---|
| vandetanib & Docetaxel | Experimental | vandetanib orally and Docetaxel intravenously Receives: Drug: Docetaxel; Drug: vandetanib |
| Placebo and Docetaxel | Active comparator | Placebo orally and docetaxel intravenously Receives: Drug: Docetaxel; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Grade 3-5 toxicity rate is the percentage of participants experiencing maximum grade of all toxicity types of grade 3-5 with any attribution on treatment during the randomized phase.
Measured: 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
Overall survival is defined from date of randomization to date of death or censored at the date the patient was last known alive.
Measured: 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
Objective response rate is defined as the percentage of participants who achieved a confirmed overall partial response (PR) or complete response (CR) using RECIST criteria on treatment during the randomized phase. Patients without measurable disease only at baseline are included, based on status of non-target lesions.Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2009 (estimated)
- Study startSep 2006
- Primary completionDec 2013
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Transitional Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 149 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, Massachusetts General Hospital, AstraZeneca
- Responsible party
- Principal investigator, Toni Choueiri, MD, Dana-Farber Cancer Institute
- Investigators
- Toni Choueiri, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00880334
- Sponsor's protocol ID
- 06-116
- Status last verified
- Aug 2018
- First submitted
- 10 Apr 2009
- Last updated
- 18 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 22184381
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Study of Docetaxel +/- Vandetanib in Metastatic TCC
- ClinicalTrials.gov ID
- NCT00880334
- Acronym / sponsor ID
- 06-116
- Conditions
- Transitional Cell Carcinoma, Bladder Cancer
- Keywords
- TCC, Zactima, docetaxel, ZD6474, taxotere
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 149 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, Massachusetts General Hospital, AstraZeneca
- Study start
- Sep 2006
- Primary completion
- Dec 2013 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 13 Apr 2009 (estimated)
- Results
- Posted 4 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| vandetanib & Docetaxel | Experimental | Drug: Docetaxel, Drug: vandetanibvandetanib orally and Docetaxel intravenously |
| Placebo and Docetaxel | Active comparator | Drug: Docetaxel, Drug: PlaceboPlacebo orally and docetaxel intravenously |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DocetaxelAlso: TaxotereGiven intravenously on Day 1 of each 21-day cycle | Drug | Placebo and Docetaxel, vandetanib & Docetaxel |
| vandetanibAlso: ZD6474, Zactimataken orally once a day, every day | Drug | vandetanib & Docetaxel |
| PlaceboTaken orally once a day every day | Drug | Placebo and Docetaxel |
Primary outcome
Median Progression-Free Survival (PFS)
Time frame: 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).
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.
3 secondary outcomes
Grade 3-5 Toxicity Rate
Time frame: 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
Time frame: 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
Time frame: 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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22184381Choueiri 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Toni Choueiri, MD principal investigator
Dana-Farber Cancer Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Docetaxel and vandetanib in people with Transitional Cell Carcinoma and Bladder Cancer, run by Dana-Farber Cancer Institute at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median Progression-Free Survival (PFS) (time frame: 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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00880334, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2018.