Randomized Study of Docetaxel +/- Vandetanib in Metastatic TCC

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00880334
• Collaborator: Brigham and Women's Hospital (Other), Beth Israel Deaconess Medical Center (Other), Massachusetts General Hospital (Other), AstraZeneca (Industry)
• Enrollment: 149
• Locations: 3
• Arms: 2
• Duration (Months): 104
• Patients Per Site: 49.7
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Transitional Cell Carcinoma; Bladder Cancer	Drug: Docetaxel; Drug: vandetanib; Drug: Placebo	Phase 2

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

• Study Type: Interventional
• Actual Enrollment: 149 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomized Study of Docetaxel +/- Vandetanib in Metastatic TCC
• Study Start Date: Sep 1, 2006
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: vandetanib & Docetaxel vandetanib orally and Docetaxel intravenously	Drug: Docetaxel; Given intravenously on Day 1 of each 21-day cycle; Other Names: Taxotere ; Drug: vandetanib; taken orally once a day, every day; Other Names: ZD6474 Zactima
Active Comparator: Placebo and Docetaxel Placebo orally and docetaxel intravenously	Drug: Docetaxel; Given intravenously on Day 1 of each 21-day cycle; Other Names: Taxotere ; Drug: Placebo; Taken orally once a day every day

Outcome Measures

Primary Outcome Measures

1. Median Progression-Free Survival (PFS) [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.

Secondary Outcome Measures

1. 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).]

   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.

2. 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).]

   Overall survival is defined from date of randomization to date of death or censored at the date the patient was last known alive.

3. 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).]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

1. 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

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02115
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115

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

Study Documents (Full-Text)

None provided.

More Information

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.

• Responsible Party: Toni Choueiri, MD, Assistant Professor of Medicine, Harvard Medical School, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00880334
• Other Study ID Numbers: 06-116; NCT00378794
• First Posted: Apr 13, 2009
• Last Update Posted: Sep 18, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Toni Choueiri, MD, Assistant Professor of Medicine, Harvard Medical School, Dana-Farber Cancer Institute: TCC; Zactima; docetaxel; ZD6474; taxotere
• Additional relevant MeSH terms: Carcinoma, Transitional Cell; Docetaxel

Study Results

Participant Flow

Recruitment Details	Patients enrolled from February 2007 through May 2010.
Pre-assignment Detail	There were 7 cancelled patients who were randomized but did not receive treatment.

Arm/Group Title	Vandetanib and Docetaxel	Placebo and Docetaxel
Arm/Group Description	Docetaxel: Given intravenously on Day 1 of each 21-day cycle Vandetanib: taken orally once a day, every day	Docetaxel: Given intravenously on Day 1 of each 21-day cycle Placebo: Taken orally once a day every day Eligible participants were allowed to crossover to single agent vandetanib.
Period Title: Randomized Phase
STARTED	74	75
Eligible & Treated	70	72
COMPLETED	70	35
NOT COMPLETED	4	40
Period Title: Randomized Phase
STARTED	0	37
COMPLETED	0	37
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Vandetanib & Docetaxel	Placebo and Docetaxel	Total
Arm/Group Description	Docetaxel: Given intravenously on Day 1 of each 21-day cycle Vandetanib: taken orally once a day, every day	Docetaxel: Given intravenously on Day 1 of each 21-day cycle Placebo: Taken orally once a day every day	Total of all reporting groups
Overall Participants	70	72	142
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	32 45.7%	39 54.2%	71 50%
>=65 years	38 54.3%	33 45.8%	71 50%
Sex: Female, Male (Count of Participants)
Female	22 31.4%	23 31.9%	45 31.7%
Male	48 68.6%	49 68.1%	97 68.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 2.9%	1 1.4%	3 2.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 4.3%	0 0%	3 2.1%
White	61 87.1%	67 93.1%	128 90.1%
More than one race	1 1.4%	0 0%	1 0.7%
Unknown or Not Reported	3 4.3%	4 5.6%	7 4.9%

Outcome Measures

1. Primary Outcome

Title	Median Progression-Free Survival (PFS)
Description	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.
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).

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all eligible and treated patients.

Arm/Group Title	Vandetanib and Docetaxel	Placebo and Docetaxel
Arm/Group Description	Docetaxel: Given intravenously on Day 1 of each 21-day cycle Vandetanib: taken orally once a day, every day	Placebo orally and docetaxel intravenously Docetaxel: Given intravenously on Day 1 of each 21-day cycle Placebo: Taken orally once a day every day
Measure Participants	70	72
Median (95% Confidence Interval) [months]	2.56	1.58

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vandetanib and Docetaxel, Placebo and Docetaxel
	Comments	The study was designed with 80% power to detect 60% improvement in median PFS from 18 to 28.8 weeks (Vandetanib+docetaxel/Placebo+docetaxel hazard ratio of 0.625) with the addition of Vandetanib while maintaining an overall significance level of 5% in a one-sided test. This assumed exponential distribution of events, accrual of 1.75 patients per week (7-8 patients per month) for 78 weeks with 34 weeks of additional follow-up (112 weeks total). Full information was 118 PFS events.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.939
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.69 to 1.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Grade 3-5 Toxicity Rate
Description	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.
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).

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all eligible and treated patients.

Arm/Group Title	Vandetanib and Docetaxel	Placebo and Docetaxel
Arm/Group Description	Docetaxel: Given intravenously on Day 1 of each 21-day cycle Vandetanib: taken orally once a day, every day	Docetaxel: Given intravenously on Day 1 of each 21-day cycle Placebo: Taken orally once a day every day
Measure Participants	70	72
Number (95% Confidence Interval) [percentage of participants]	73 104.3%	57 79.2%

3. Secondary Outcome

Title	Median Overall Survival
Description	Overall survival is defined from date of randomization to date of death or censored at the date the patient was last known alive.
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).

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all eligible and treated patients.

Arm/Group Title	Vandetanib and Docetaxel	Placebo and Docetaxel
Arm/Group Description	Docetaxel: Given intravenously on Day 1 of each 21-day cycle Vandetanib: taken orally once a day, every day	Docetaxel: Given intravenously on Day 1 of each 21-day cycle Placebo: Taken orally once a day every day
Measure Participants	70	72
Median (95% Confidence Interval) [months]	5.85	7.03

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vandetanib and Docetaxel, Placebo and Docetaxel
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.873
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Objective Response Rate
Description	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.
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).

Outcome Measure Data

Analysis Population Description

The analysis dataset is comprised of all eligible and treated patients.

Arm/Group Title	Vandetanib and Docetaxel	Placebo and Docetaxel
Arm/Group Description	Docetaxel: Given intravenously on Day 1 of each 21-day cycle Vandetanib: taken orally once a day, every day	Docetaxel: Given intravenously on Day 1 of each 21-day cycle Placebo: Taken orally once a day every day
Measure Participants	70	72
Number (95% Confidence Interval) [percentage of participants]	7.1 10.1%	11.1 15.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vandetanib and Docetaxel, Placebo and Docetaxel
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.56
	Comments
	Method	Fisher Exact
	Comments

5. Post-Hoc Outcome

Title	Disease Control Rate
Description	Disease control rate is defined as the percentage of participants with confirmed overall Stable Disease (SD) or better using RECIST 1.0 criteria which parallels absence of disease progression (PD) on treatment during the randomized phase. 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. Patients without measurable disease only at baseline are included, based on status of non-target lesions.
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).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib and Docetaxel	Placebo and Docetaxel
Arm/Group Description	Docetaxel: Given intravenously on Day 1 of each 21-day cycle Vandetanib: taken orally once a day, every day	Docetaxel: Given intravenously on Day 1 of each 21-day cycle Placebo: Taken orally once a day every day
Measure Participants	70	72
Number (95% Confidence Interval) [percentage of participants]	51 72.9%	42 58.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vandetanib and Docetaxel, Placebo and Docetaxel
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.31
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	Assessed each cycle throughout treatment on the randomized and crossover phases from time of first dose and up to day 30 post-treatment. Median treatment duration for the randomized study cohort was 2 cycles (range 1-31 cycles). Median treatment duration for the crossover study cohort was 2 cycles (range 1-23 cycles).
Adverse Event Reporting Description	Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with vandetanib treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with vandetanib treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3. No further data is available to specify classification of other beyond the general term.
Arm/Group Title	Vandetanib and Docetaxel		Placebo and Docetaxel		Placebo and Docetaxel-Crossover
Arm/Group Description	Docetaxel: Given intravenously on Day 1 of each 21-day cycle Vandetanib: taken orally once a day, every day		Docetaxel: Given intravenously on Day 1 of each 21-day cycle Placebo: Taken orally once a day every day		Docetaxel: Given intravenously on Day 1 of each 21-day cycle Vandetanib: taken orally once a day, every day
All Cause Mortality
	Vandetanib and Docetaxel		Placebo and Docetaxel		Placebo and Docetaxel-Crossover
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Vandetanib and Docetaxel		Placebo and Docetaxel		Placebo and Docetaxel-Crossover
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/70 (60%)		26/72 (36.1%)		6/37 (16.2%)
Blood and lymphatic system disorders
Febrile neutropenia	1/70 (1.4%)		2/72 (2.8%)		0/37 (0%)
Hemoglobin	3/70 (4.3%)		1/72 (1.4%)		0/37 (0%)
Gastrointestinal disorders
Diarrhea w/o prior colostomy	5/70 (7.1%)		0/72 (0%)		0/37 (0%)
Esophagitis	0/70 (0%)		1/72 (1.4%)		0/37 (0%)
GI-other	0/70 (0%)		1/72 (1.4%)		0/37 (0%)
Vomiting	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Vomiting	0/70 (0%)		0/72 (0%)		1/37 (2.7%)
General disorders
Fatigue	6/70 (8.6%)		4/72 (5.6%)		2/37 (5.4%)
Nausea	0/70 (0%)		0/72 (0%)		1/37 (2.7%)
Immune system disorders
Allergic reaction	0/70 (0%)		1/72 (1.4%)		0/37 (0%)
Infections and infestations
Infection Gr0-2 neut, bladder	0/70 (0%)		1/72 (1.4%)		0/37 (0%)
Infection Gr 0-2 neut, blood	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Infection Gr0-2 neut, lung	1/70 (1.4%)		1/72 (1.4%)		0/37 (0%)
Infection w/ gr 3-4 neut, blood	0/70 (0%)		1/72 (1.4%)		0/37 (0%)
Infection w/ gr3-4 neut, lung	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Infection w/ unk ANC bladder	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Infection w/ unk ANC peritoneal cavity	0/70 (0%)		1/72 (1.4%)		0/37 (0%)
Infection Gr0-2 neut, urinary tract	0/70 (0%)		0/72 (0%)		1/37 (2.7%)
Injury, poisoning and procedural complications
Vascular access,Thrombosis/embolism	0/70 (0%)		1/72 (1.4%)		0/37 (0%)
Investigations
Creatinine	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Leukocytes	5/70 (7.1%)		7/72 (9.7%)		0/37 (0%)
Lymphopenia	4/70 (5.7%)		1/72 (1.4%)		0/37 (0%)
Neutrophils	10/70 (14.3%)		10/72 (13.9%)		0/37 (0%)
PTT	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
QTc interval	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Metabolism and nutrition disorders
Anorexia	1/70 (1.4%)		1/72 (1.4%)		0/37 (0%)
Dehydration	2/70 (2.9%)		1/72 (1.4%)		0/37 (0%)
Hyperglycemia	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Hyponatremia	2/70 (2.9%)		1/72 (1.4%)		1/37 (2.7%)
Hypophosphatemia	5/70 (7.1%)		3/72 (4.2%)		0/37 (0%)
Musculoskeletal and connective tissue disorders
Back, pain	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Joint, pain	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Muscle, pain	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Nonneuropathic generalized weakness	1/70 (1.4%)		1/72 (1.4%)		0/37 (0%)
Nervous system disorders
Neuropathy-sensory	2/70 (2.9%)		0/72 (0%)		0/37 (0%)
Syncope	0/70 (0%)		1/72 (1.4%)		0/37 (0%)
Psychiatric disorders
Depression	0/70 (0%)		1/72 (1.4%)		0/37 (0%)
Renal and urinary disorders
Urinary frequency/urgency	0/70 (0%)		1/72 (1.4%)		0/37 (0%)
Urinary retention	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Urinary hemorrhage NOS	0/70 (0%)		0/72 (0%)		1/37 (2.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/70 (2.9%)		1/72 (1.4%)		2/37 (5.4%)
Pulmonary/Upper Respiratory-other	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Skin and subcutaneous tissue disorders
Erythema multiforme	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Photosensitivity	3/70 (4.3%)		0/72 (0%)		0/37 (0%)
Rash/desquamation	5/70 (7.1%)		0/72 (0%)		0/37 (0%)
Rash: acne/acneiform	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Skin-other	2/70 (2.9%)		0/72 (0%)		0/37 (0%)
Ulceration	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Vascular disorders
Hypertension	0/70 (0%)		1/72 (1.4%)		1/37 (2.7%)
Thrombosis/thrombus/embolism	0/70 (0%)		1/72 (1.4%)		0/37 (0%)
Other (Not Including Serious) Adverse Events
	Vandetanib and Docetaxel		Placebo and Docetaxel		Placebo and Docetaxel-Crossover
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/70 (31.4%)		12/72 (16.7%)		5/37 (13.5%)
Blood and lymphatic system disorders
Febrile neutropenia	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Hematologic-other	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Hemoglobin	1/70 (1.4%)		1/72 (1.4%)		1/37 (2.7%)
Cardiac disorders
Atrial fibrillation	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Atrial flutter	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Palpitations	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Eye disorders
Dry eye syndrome	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Vision-blurred	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Gastrointestinal disorders
Abdomen, pain	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Diarrhea w/o prior colostomy	6/70 (8.6%)		0/72 (0%)		1/37 (2.7%)
Dyspepsia	2/70 (2.9%)		0/72 (0%)		0/37 (0%)
Dysphagia	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Flatulence	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
GI-other	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Muco/stomatitis by exam, oral cavity	1/70 (1.4%)		1/72 (1.4%)		0/37 (0%)
Muco/stomatitis by exam, stomach	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Nausea	4/70 (5.7%)		3/72 (4.2%)		0/37 (0%)
General disorders
Constitutional, other	0/70 (0%)		1/72 (1.4%)		0/37 (0%)
Edema head and neck	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Edema limb	3/70 (4.3%)		1/72 (1.4%)		0/37 (0%)
Edema trunk/genital	2/70 (2.9%)		0/72 (0%)		0/37 (0%)
Fatigue	9/70 (12.9%)		6/72 (8.3%)		3/37 (8.1%)
Fever w/o neutropenia	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Rigors/chills	2/70 (2.9%)		0/72 (0%)		0/37 (0%)
Infections and infestations
Infection Gr0-2 neut, oral cavity	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Infection w/ gr3-4 neut, bladder	0/70 (0%)		1/72 (1.4%)		0/37 (0%)
Infection w/ unk ANC skin (cellulitis)	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Investigations
Alkaline phosphatase	0/70 (0%)		1/72 (1.4%)		0/37 (0%)
Bilirubin	1/70 (1.4%)		0/72 (0%)		1/37 (2.7%)
Leukocytes	1/70 (1.4%)		1/72 (1.4%)		0/37 (0%)
Lymphopenia	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
AST, SGOT	0/70 (0%)		0/72 (0%)		1/37 (2.7%)
ALT, SGPT	0/70 (0%)		0/72 (0%)		1/37 (2.7%)
Alkaline phosphatase	0/70 (0%)		0/72 (0%)		1/37 (2.7%)
Metabolism and nutrition disorders
Anorexia	3/70 (4.3%)		1/72 (1.4%)		1/37 (2.7%)
Dehydration	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Hyperglycemia	2/70 (2.9%)		1/72 (1.4%)		0/37 (0%)
Hyperkalemia	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Hypoalbuminemia	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Hypokalemia	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Hypomagnesemia	4/70 (5.7%)		0/72 (0%)		0/37 (0%)
Hyponatremia	2/70 (2.9%)		0/72 (0%)		0/37 (0%)
Musculoskeletal and connective tissue disorders
Extremity-limb, pain	2/70 (2.9%)		0/72 (0%)		1/37 (2.7%)
Joint, pain	0/70 (0%)		1/72 (1.4%)		0/37 (0%)
Muscle, pain	2/70 (2.9%)		1/72 (1.4%)		0/37 (0%)
Nonneuropathic generalized weakness	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Nonneuropathic lower extr muscle weak	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Musculoskeletal/soft tissue-other	0/70 (0%)		0/72 (0%)		1/37 (2.7%)
Nervous system disorders
Dizziness	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Head/headache	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Neurologic-other	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Neuropathy-motor	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Neuropathy-sensory	2/70 (2.9%)		2/72 (2.8%)		1/37 (2.7%)
Taste disturbance	3/70 (4.3%)		1/72 (1.4%)		1/37 (2.7%)
Tremor	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Psychiatric disorders
Insomnia	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Renal and urinary disorders
Proteinuria	0/70 (0%)		1/72 (1.4%)		0/37 (0%)
Renal failure	0/70 (0%)		1/72 (1.4%)		0/37 (0%)
Urinary hemorrhage NOS	2/70 (2.9%)		0/72 (0%)		0/37 (0%)
Reproductive system and breast disorders
Pelvic, pain	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary, hemorrhage	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Respiratory tract hemorrhage NOS	0/70 (0%)		1/72 (1.4%)		0/37 (0%)
Cough	0/70 (0%)		0/72 (0%)		1/37 (2.7%)
Pulmonary/Upper Respiratory-other	0/70 (0%)		0/72 (0%)		1/37 (2.7%)
Skin and subcutaneous tissue disorders
Alopecia	3/70 (4.3%)		1/72 (1.4%)		0/37 (0%)
Dry skin	2/70 (2.9%)		1/72 (1.4%)		0/37 (0%)
Erythema multiforme	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Nail changes	1/70 (1.4%)		0/72 (0%)		1/37 (2.7%)
Photosensitivity	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Pruritus/itching	2/70 (2.9%)		0/72 (0%)		0/37 (0%)
Rash/desquamation	0/70 (0%)		1/72 (1.4%)		0/37 (0%)
Rash: acne/acneiform	0/70 (0%)		1/72 (1.4%)		0/37 (0%)
Skin-other	0/70 (0%)		1/72 (1.4%)		0/37 (0%)
Vascular disorders
Flushing	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Hypertension	1/70 (1.4%)		0/72 (0%)		0/37 (0%)
Hemorrhage-other	0/70 (0%)		0/72 (0%)		1/37 (2.7%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.