ZODIAC: ZACTIMA (an Anti-EGFR / Anti-VEGF Agent) Combined With Docetaxel Compared to Docetaxel in Non-small Cell Lung Cancer

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00312377
• Collaborator: (none)
• Enrollment: 1,690
• Locations: 157
• Arms: 2
• Duration (Months): 94
• Patients Per Site: 10.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This large phase III clinical study is studying the effect of vandetanib (ZACTIMA) in treating non-small cell lung cancer (NSCLC). Vandetanib is a new type of agent that targets the blood supply to a cancer tumour (through it's anti-vascular endothelial growth factor receptor (VEGFR) properties) and the tumour cells themselves (through it's anti-endothelial growth factor receptor (EGFR) actions). This study will look at the effects of vandetanib in lung cancer patients who have had their cancer re-appear after treatment with standard chemotherapy.

This clinical study will test if the vandetanib anti-VEGF and anti-EGFR characteristics can deliver longer improved progression free survival and improved overall survival than docetaxel (Taxotere) alone.

All patients participating this clinical study will receive treatment with docetaxel, a commonly used treatment for recurrent non-small cell lung cancer.

In addition, some patients will also receive vandetanib (ZACTIMA), an anti-EGFR / anti-VEGF agent.

Recent clinical research shows that vascular endothelial growth factor receptor (VEGFR) inhibition, when used with standard chemotherapy, can lead to increased survival in advanced non-small cell lung cancer (NSCLC) patients.

Other research shows that epidermal growth factor receptor (EGFR) inhibitors, like erlotinib (Tarceva) can also increase overall non-small cell lung cancer survival by killing tumour cells and stopping them from dividing.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer; Lung Cancer	Drug: Docetaxel; Drug: Vandetanib	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1690 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III, Randomized, Double-Blinded, Multi-Center, Study to Assess the Efficacy of Docetaxel (TAXOTERE™) in Combination With ZD6474 (ZACTIMA™) Versus Docetaxel (TAXOTERE™) With Placebo in Subjects With Locally Advanced or Metastatic NSCLC
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Docetaxel monotherapy	Drug: Docetaxel; infusion; Other Names: TAXOTERE™
Experimental: 2 Vandetanib + Docetaxel	Drug: Docetaxel; infusion; Other Names: TAXOTERE™ ; Drug: Vandetanib; oral; Other Names: ZACTIMA™ ZD6474

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) in the Overall Population [RECIST tumour assessments carried out every 6 weeks from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first assessed up to 24 months]

   Median time (in weeks) from randomisation until objective disease progression or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment. Progression was derived according to RECIST 1.0 and is defined as an increase of at least 20% in the total tumour size of measurable lesions over the nadir measurement, unequivocal progression in the non-target lesions or the appearance of one or more new lesions.

2. Progression-Free Survival (PFS) in the Female Population [RECIST tumour assessments carried out every 6 weeks from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first assessed up to 24 months]

   Median time (in weeks) from randomisation until objective disease progression or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment. Progression was derived according to RECIST 1.0 and is defined as an increase of at least 20% in the total tumour size of measurable lesions over the nadir measurement, unequivocal progression in the non-target lesions or the appearance of one or more new lesions.

Secondary Outcome Measures

1. Overall Survival (OS) in the Overall Population [Time to death in months]

   Overall survival is defined as the time from date of randomization until death. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive (ie their status must be known at the censored date and should not be lost to follow up or unknown).

2. Overall Survival (OS) in the Female Population [Time to death in months]

   Overall survival is defined as the time from date of randomization until death. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive (ie their status must be known at the censored date and should not be lost to follow up or unknown).

3. Objective Response Rate (ORR) [Each patient was assessed for objective response from the sequence of RECIST scan data up to data cut off. RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression]

   The ORR is the number of patients that are responders ie those patients with a confirmed best objective response of complete response (CR) or partial response (PR) as determined according to RECIST 1.0. CR is defined as the disappearance of all target lesions with no evidence of tumour elsewhere and PR is defined as at least a 30% reduction in the total tumour size of measurable lesions with no new lesions and no progression in the non-target lesions.

4. Disease Control Rate (DCR) [RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression]

   Disease control rate is defined as the number of patients who achieved disease control at least 6 weeks following randomisation. Disease control at 6 weeks is defined as a best objective response of complete response (CR), partial response (PR) or stable disease (SD) >= 6 weeks as determined according to RECIST 1.0. CR is defined as the disappearance of all target lesions with no evidence of tumour elsewhere, PR is defined as at least a 30% reduction in the total tumour size of measurable lesions with no new lesions and no progression in the non-target lesions and SD >= 6 is assigned to patients who have not responded and have no evidence of progression at least 6 weeks after randomisation.

5. Duration of Response (DoR) [RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression]

   Response is defined as a confirmed best objective response of CR or PR. Duration of response is defined as time from the date of first documented response until date of documented progression or death in the absence of disease progression (provided death is within 3 months of last RECIST assessment)

6. Time to Deterioration of Disease-related Symptoms (TDS) by Functional Assessment of Cancer Therapy - Lung (FACT-L) Lung Cancer Subscale (LCS). [FACT-L questionnaires are to be administered every 3 weeks after randomisation]

   The lung cancer subscale (LCS) consists of 7 items of the FACT-L (3 items relating to breathing/dyspnea, and 1 item each relating to cough, weight loss, appetite, and cognition). The LCS total score is the sum of the scores from the 7 items. Time to deterioration is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 21 days. A patient will be defined as having a deterioration in symptoms if they have a single visit assessment of 'worsened' with no visit assessment of 'improved' within the next 21 days.

7. Time to Deterioration of Disease-related Symptoms (TDS) by FACT-L Pulmonary Symptom Index (PSI) [FACT-L questionnaires are to be administered every 3 weeks after randomisation]

   The pulmonary symptom index (PSI) consists of 4 items of the LCS relating to pulmonary symptoms (i.e. 3 items relating to breathing/dyspnea, and 1 item relating to cough). The PSI score is the sum of the scores from the 4 items. Time to deterioration is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 21 days. A patient will be defined as having a deterioration in symptoms if they have a single visit assessment of 'worsened' with no visit assessment of 'improved' within the next 21 days.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

Lung cancer patients who answer true to the following statements are eligible to join this clinical study.

• I have a confirmed diagnosis of locally advanced or metastatic non small cell lung cancer (Stage IIIb - IV)

• I have had 1st line anti-cancer therapy. Previous treatment with Avastin (bevacizumab) in first line NSCLC is allowed.

Exclusion Criteria:

Lung cancer patients who answer true to the following are NOT eligible to join this clinical study.

• I do not have non small cell lung cancer (NSCLC)

• I have received treatment with docetaxel (Taxotere). Prior treatment with paclitaxel is acceptable.

• I have received 2nd line anti-cancer therapy (For example, patients with previous 2nd line non small cell lung cancer (NSCLC) treatment with Tarceva (erlotinib, OSI-744), Alimta (pemetrexed) are not eligible)

• I have been treated with VEGFR-tyrosine kinase inhibitors (TKIs) (sunitinib, sorafenib, other VEGF TKIs). Previous treatment with Avastin (bevacizumab) in 1st line non small cell lung cancer is permitted.

• I have a history of uncontrolled irregular heartbeat

• I have a history of high blood pressure which has not been controlled with medication If you are unsure of the meaning of the inclusion and exclusion criteria above, please contact the call center number for help.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Fullerton	California	United States
2	Research Site	Los Angeles	California	United States
3	Research Site	Northridge	California	United States
4	Research Site	Colorado Springs	Colorado	United States
5	Research Site	Norwalk	Connecticut	United States
6	Research Site	Ocala	Florida	United States
7	Research Site	Marietta	Georgia	United States
8	Research Site	Joliet	Illinois	United States
9	Research Site	Park Ridge	Illinois	United States
10	Research Site	Hutchinson	Kansas	United States
11	Research Site	Louisville	Kentucky	United States
12	Research Site	Boston	Massachusetts	United States
13	Research Site	Ann Arbor	Michigan	United States
14	Research Site	St. Louis	Missouri	United States
15	Research Site	Henderson	Nevada	United States
16	Research Site	Albany	New York	United States
17	Research Site	Armonk	New York	United States
18	Research Site	New York	New York	United States
19	Research Site	Durham	North Carolina	United States
20	Research Site	Hickory	North Carolina	United States
21	Research Site	Portland	Oregon	United States
22	Research Site	Austin	Texas	United States
23	Research Site	Houston	Texas	United States
24	Research Site	Ogden	Utah	United States
25	Research Site	Alexandria	Virginia	United States
26	Research Site	Salem	Virginia	United States
27	Research Site	Vancouver	Washington	United States
28	Research Site	Bahía Blanca		Argentina
29	Research Site	Capital Federal		Argentina
30	Research Site	Ciudad de Buenos Aires		Argentina
31	Research Site	Mendoza		Argentina
32	Research Site	Rosario		Argentina
33	Research Site	Graz		Austria
34	Research Site	Grimmenstein		Austria
35	Research Site	Innsbruck		Austria
36	Research Site	Linz		Austria
37	Research Site	Wels		Austria
38	Research Site	Wien		Austria
39	Research Site	Brussels (Jette)		Belgium
40	Research Site	Brussels (Woluwé-St-Lambert)		Belgium
41	Research Site	Edegem		Belgium
42	Research Site	Genk		Belgium
43	Research Site	Liege		Belgium
44	Research Site	Fortaleza		Brazil
45	Research Site	Goiânia		Brazil
46	Research Site	Porto Alegre		Brazil
47	Research Site	Rio de Janeiro		Brazil
48	Research Site	Sao Paulo		Brazil
49	Research Site	Edmonton	Alberta	Canada
50	Research Site	Moncton	New Brunswick	Canada
51	Research Site	Halifax	Nova Scotia	Canada
52	Research Site	Kitchener	Ontario	Canada
53	Research Site	London	Ontario	Canada
54	Research Site	Toronto	Ontario	Canada
55	Research Site	Laval	Quebec	Canada
56	Research Site	Quebec		Canada
57	Research Site	Beijing		China
58	Research Site	Chongqing		China
59	Research Site	Guangzhou		China
60	Research Site	Nanjing		China
61	Research Site	Shanghai		China
62	Research Site	Wuhan		China
63	Research Site	Herlev		Denmark
64	Research Site	København Ø		Denmark
65	Research Site	Odense		Denmark
66	Research Site	Roskilde		Denmark
67	Research Site	Vejle		Denmark
68	Research Site	Bordeaux Cedex		France
69	Research Site	Boulogne Billancourt		France
70	Research Site	Caen Cedex		France
71	Research Site	Dijon		France
72	Research Site	Nancy		France
73	Research Site	Paris		France
74	Research Site	Pierre Benite Cedex		France
75	Research Site	Saint Herblain		France
76	Research Site	Bad Berka		Germany
77	Research Site	Berlin		Germany
78	Research Site	Essen		Germany
79	Research Site	Großhansdorf		Germany
80	Research Site	Halle		Germany
81	Research Site	Hamburg		Germany
82	Research Site	Heidelberg		Germany
83	Research Site	Köln		Germany
84	Research Site	Oldenburg		Germany
85	Research Site	Ulm		Germany
86	Research Site	Wiesbaden		Germany
87	Research Site	Athens		Greece
88	Research Site	Heraklion		Greece
89	Research Site	Ahmedabad		India
90	Research Site	Chennai		India
91	Research Site	Hyderabad		India
92	Research Site	Kolkata		India
93	Research Site	New Delhi		India
94	Research Site	Pune		India
95	Research Site	Vellore		India
96	Research Site	Jakarta Timur		Indonesia
97	Research Site	Yogyakarta		Indonesia
98	Research Site	Ancona		Italy
99	Research Site	Avellino		Italy
100	Research Site	Bologna		Italy
101	Research Site	Genova		Italy
102	Research Site	Mantova		Italy
103	Research Site	Napoli		Italy
104	Research Site	Orbassano		Italy
105	Research Site	Parma		Italy
106	Research Site	Perugia		Italy
107	Research Site	Pisa		Italy
108	Research Site	Reggio Emilia		Italy
109	Research Site	Akashi-shi		Japan
110	Research Site	Fukuoka-shi		Japan
111	Research Site	Fukuoka		Japan
112	Research Site	Isehara-shi		Japan
113	Research Site	Kobe-shi		Japan
114	Research Site	Koto-ku		Japan
115	Research Site	Kumamoto-shi		Japan
116	Research Site	Matsuyama-shi		Japan
117	Research Site	Nagoya-shi		Japan
118	Research Site	Okayama-shi		Japan
119	Research Site	Okazaki-shi		Japan
120	Research Site	Osaka-shi		Japan
121	Research Site	Osakasayama-shi		Japan
122	Research Site	Sakai-shi		Japan
123	Research Site	Sapporo-shi		Japan
124	Research Site	Shinjuku-ku		Japan
125	Research Site	Sunto-gun		Japan
126	Research Site	Toyonaka		Japan
127	Research Site	Ube-shi		Japan
128	Research Site	Utsunomiya-shi		Japan
129	Research Site	Yokohama-shi		Japan
130	Research Site	Seoul		Korea, Republic of
131	Research Site	Kubang Kerian		Malaysia
132	Research Site	Nilai		Malaysia
133	Research Site	Penang		Malaysia
134	Research Site	Durango		Mexico
135	Research Site	Morelia		Mexico
136	Research Site	Toluca		Mexico
137	Research Site	Amsterdam		Netherlands
138	Research Site	Den Bosch		Netherlands
139	Research Site	Groningen		Netherlands
140	Research Site	Maastricht		Netherlands
141	Research Site	Coimbra		Portugal
142	Research Site	Funchal		Portugal
143	Research Site	Lisboa		Portugal
144	Research Site	Porto		Portugal
145	Research Site	Vila Nova de Gaia		Portugal
146	Research Site	Singapore		Singapore
147	Research Site	A Coruña		Spain
148	Research Site	Alicante		Spain
149	Research Site	Madrid		Spain
150	Research Site	Málaga		Spain
151	Research Site	Zaragoza		Spain
152	Research Site	Chiang Mai		Thailand
153	Research Site	Ankara		Turkey
154	Research Site	Istanbul		Turkey
155	Research Site	Izmir		Turkey
156	Research Site	Hanoi city		Vietnam
157	Research Site	Ho Chi Minh city		Vietnam

Sponsors and Collaborators

• Genzyme, a Sanofi Company

Investigators

• Study Director: [e-mail], Sanofi

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• CSR-D4200C00032.pdf
• CSP Redacted

Publications

None provided.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT00312377
• Other Study ID Numbers: D4200C00032; 6474IL/0032; 2005-004749-32
• First Posted: Apr 10, 2006
• Last Update Posted: Sep 30, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by Genzyme, a Sanofi Company: Non-small cell lung cancer; NSCLC
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Docetaxel

Study Results

Participant Flow

Recruitment Details	First patient enrolled 08 May 2006, last patient enrolled 14 March 2008, cut off date 22 August 2008

Arm/Group Title	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description	Vandetanib 100 mg oral tablet taken once daily in combination with docetaxel 75 mg/m2 IVb infusion every 21 days up to a maximum of 6 cycles	Placebo tablet taken once daily plus docetaxel 75 mg/m2 IVb infusion every 21 days up to a maximum of 6 cycles
Period Title: Overall Study
STARTED	694	697
COMPLETED	50	29
NOT COMPLETED	644	668

Baseline Characteristics

Arm/Group Title	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel	Total
Arm/Group Description	Vandetanib 100 mg plus docetaxel	Placebo plus docetaxel	Total of all reporting groups
Overall Participants	694	697	1391
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	58.5	58.4	58.45
Sex: Female, Male (Count of Participants)
Female	497 71.6%	473 67.9%	970 69.7%
Male	197 28.4%	224 32.1%	421 30.3%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS) in the Overall Population
Description	Median time (in weeks) from randomisation until objective disease progression or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment. Progression was derived according to RECIST 1.0 and is defined as an increase of at least 20% in the total tumour size of measurable lesions over the nadir measurement, unequivocal progression in the non-target lesions or the appearance of one or more new lesions.
Time Frame	RECIST tumour assessments carried out every 6 weeks from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first assessed up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description	Vandetanib 100 mg plus docetaxel	Placebo plus docetaxel
Measure Participants	694	697
Median (95% Confidence Interval) [Weeks]	17.3	14

2. Primary Outcome

Title	Progression-Free Survival (PFS) in the Female Population
Description	Median time (in weeks) from randomisation until objective disease progression or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment. Progression was derived according to RECIST 1.0 and is defined as an increase of at least 20% in the total tumour size of measurable lesions over the nadir measurement, unequivocal progression in the non-target lesions or the appearance of one or more new lesions.
Time Frame	RECIST tumour assessments carried out every 6 weeks from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first assessed up to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description	Vandetanib 100 mg plus docetaxel	Placebo plus docetaxel
Measure Participants	197	224
Median (95% Confidence Interval) [Weeks]	20.1	18.3

3. Secondary Outcome

Title	Overall Survival (OS) in the Overall Population
Description	Overall survival is defined as the time from date of randomization until death. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive (ie their status must be known at the censored date and should not be lost to follow up or unknown).
Time Frame	Time to death in months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description	Vandetanib 100 mg plus docetaxel	Placebo plus docetaxel
Measure Participants	694	697
Median (95% Confidence Interval) [Months]	10.6	10

4. Secondary Outcome

Title	Overall Survival (OS) in the Female Population
Description	Overall survival is defined as the time from date of randomization until death. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive (ie their status must be known at the censored date and should not be lost to follow up or unknown).
Time Frame	Time to death in months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description	Vandetanib 100 mg plus docetaxel	Placebo plus docetaxel
Measure Participants	197	224
Median (95% Confidence Interval) [Months]	12.7	14.2

5. Secondary Outcome

Title	Objective Response Rate (ORR)
Description	The ORR is the number of patients that are responders ie those patients with a confirmed best objective response of complete response (CR) or partial response (PR) as determined according to RECIST 1.0. CR is defined as the disappearance of all target lesions with no evidence of tumour elsewhere and PR is defined as at least a 30% reduction in the total tumour size of measurable lesions with no new lesions and no progression in the non-target lesions.
Time Frame	Each patient was assessed for objective response from the sequence of RECIST scan data up to data cut off. RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description	Vandetanib 100 mg plus docetaxel	Placebo plus docetaxel
Measure Participants	694	697
Number [Participants]	120 17.3%	71 10.2%

6. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	Disease control rate is defined as the number of patients who achieved disease control at least 6 weeks following randomisation. Disease control at 6 weeks is defined as a best objective response of complete response (CR), partial response (PR) or stable disease (SD) >= 6 weeks as determined according to RECIST 1.0. CR is defined as the disappearance of all target lesions with no evidence of tumour elsewhere, PR is defined as at least a 30% reduction in the total tumour size of measurable lesions with no new lesions and no progression in the non-target lesions and SD >= 6 is assigned to patients who have not responded and have no evidence of progression at least 6 weeks after randomisation.
Time Frame	RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description	Vandetanib 100 mg plus docetaxel	Placebo plus docetaxel
Measure Participants	694	697
Number [Participants]	413 59.5%	380 54.5%

7. Secondary Outcome

Title	Duration of Response (DoR)
Description	Response is defined as a confirmed best objective response of CR or PR. Duration of response is defined as time from the date of first documented response until date of documented progression or death in the absence of disease progression (provided death is within 3 months of last RECIST assessment)
Time Frame	RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description	Vandetanib 100 mg plus docetaxel	Placebo plus docetaxel
Measure Participants	694	697
Median (Full Range) [Weeks]	29.9	19.7

8. Secondary Outcome

Title	Time to Deterioration of Disease-related Symptoms (TDS) by Functional Assessment of Cancer Therapy - Lung (FACT-L) Lung Cancer Subscale (LCS).
Description	The lung cancer subscale (LCS) consists of 7 items of the FACT-L (3 items relating to breathing/dyspnea, and 1 item each relating to cough, weight loss, appetite, and cognition). The LCS total score is the sum of the scores from the 7 items. Time to deterioration is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 21 days. A patient will be defined as having a deterioration in symptoms if they have a single visit assessment of 'worsened' with no visit assessment of 'improved' within the next 21 days.
Time Frame	FACT-L questionnaires are to be administered every 3 weeks after randomisation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description	Vandetanib 100 mg plus docetaxel	Placebo plus docetaxel
Measure Participants	694	697
Median (Inter-Quartile Range) [Weeks]	15	11.9

9. Secondary Outcome

Title	Time to Deterioration of Disease-related Symptoms (TDS) by FACT-L Pulmonary Symptom Index (PSI)
Description	The pulmonary symptom index (PSI) consists of 4 items of the LCS relating to pulmonary symptoms (i.e. 3 items relating to breathing/dyspnea, and 1 item relating to cough). The PSI score is the sum of the scores from the 4 items. Time to deterioration is defined as the interval from the date of randomization to the first assessment of worsened without an improvement in the next 21 days. A patient will be defined as having a deterioration in symptoms if they have a single visit assessment of 'worsened' with no visit assessment of 'improved' within the next 21 days.
Time Frame	FACT-L questionnaires are to be administered every 3 weeks after randomisation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vandetanib 100 mg Plus Docetaxel	Placebo Plus Docetaxel
Arm/Group Description	Vandetanib 100 mg plus docetaxel	Placebo plus docetaxel
Measure Participants	694	697
Median (Inter-Quartile Range) [Weeks]	12.3	11.9

Adverse Events

Arm/Group Title	Vandetanib 100 mg Plus Docetaxel		Placebo Plus Docetaxel
Arm/Group Description	Vandetanib 100 mg plus docetaxel		Placebo plus docetaxel
All Cause Mortality
	Vandetanib 100 mg Plus Docetaxel		Placebo Plus Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Vandetanib 100 mg Plus Docetaxel		Placebo Plus Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	263/694 (37.9%)		232/697 (33.3%)
Blood and lymphatic system disorders
Febrile Neutropenia	46/694 (6.6%)		38/697 (5.5%)
Neutropenia	16/694 (2.3%)		18/697 (2.6%)
Anaemia	4/694 (0.6%)		6/697 (0.9%)
Leukopenia	3/694 (0.4%)		2/697 (0.3%)
Leukocytosis	0/694 (0%)		2/697 (0.3%)
Bone Marrow Failure	1/694 (0.1%)		0/697 (0%)
Febrile Bone Marrow Aplasia	1/694 (0.1%)		0/697 (0%)
Iron Deficiency Anaemia	1/694 (0.1%)		0/697 (0%)
Thrombocytopenia	1/694 (0.1%)		1/697 (0.1%)
Cardiac disorders
Atrial Fibrillation	3/694 (0.4%)		10/697 (1.4%)
Myocardial Infarction	0/694 (0%)		4/697 (0.6%)
Cardiac Arrest	1/694 (0.1%)		3/697 (0.4%)
Cardiac Failure	0/694 (0%)		3/697 (0.4%)
Acute Myocardial Infarction	2/694 (0.3%)		2/697 (0.3%)
Atrial Flutter	2/694 (0.3%)		1/697 (0.1%)
Angina Unstable	1/694 (0.1%)		0/697 (0%)
Arrhythmia	0/694 (0%)		1/697 (0.1%)
Atrioventricular Block Complete	1/694 (0.1%)		0/697 (0%)
Atrioventricular Block Second Degree	0/694 (0%)		1/697 (0.1%)
Cardiac Tamponade	0/694 (0%)		1/697 (0.1%)
Cardio-Respiratory Arrest	1/694 (0.1%)		0/697 (0%)
Extrasystoles	1/694 (0.1%)		0/697 (0%)
Pericardial Effusion	1/694 (0.1%)		0/697 (0%)
Pericarditis	0/694 (0%)		1/697 (0.1%)
Supraventricular Tachycardia	1/694 (0.1%)		0/697 (0%)
Tachyarrhythmia	0/694 (0%)		1/697 (0.1%)
Tachycardia	1/694 (0.1%)		0/697 (0%)
Ventricular Extrasystoles	0/694 (0%)		1/697 (0.1%)
Congenital, familial and genetic disorders
Hereditary Angioedema	1/694 (0.1%)		0/697 (0%)
Ear and labyrinth disorders
Deafness Unilateral	1/694 (0.1%)		0/697 (0%)
Vertigo	1/694 (0.1%)		0/697 (0%)
Eye disorders
Ocular Surface Disease	1/694 (0.1%)		0/697 (0%)
Retinal Artery Occlusion	1/694 (0.1%)		0/697 (0%)
Gastrointestinal disorders
Diarrhoea	14/694 (2%)		11/697 (1.6%)
Vomiting	7/694 (1%)		8/697 (1.1%)
Nausea	5/694 (0.7%)		4/697 (0.6%)
Abdominal Pain Upper	4/694 (0.6%)		1/697 (0.1%)
Constipation	0/694 (0%)		3/697 (0.4%)
Gastric Ulcer	0/694 (0%)		3/697 (0.4%)
Abdominal Pain	2/694 (0.3%)		1/697 (0.1%)
Gastrointestinal Haemorrhage	1/694 (0.1%)		2/697 (0.3%)
Stomatitis	2/694 (0.3%)		0/697 (0%)
Appendicitis Perforated	1/694 (0.1%)		0/697 (0%)
Ascites	0/694 (0%)		1/697 (0.1%)
Dyspepsia	0/694 (0%)		1/697 (0.1%)
Dysphagia	1/694 (0.1%)		1/697 (0.1%)
Enteritis	1/694 (0.1%)		0/697 (0%)
Enterocolitis	1/694 (0.1%)		0/697 (0%)
Gastric Haemorrhage	0/694 (0%)		1/697 (0.1%)
Gastritis	0/694 (0%)		1/697 (0.1%)
Gastrointestinal Inflammation	1/694 (0.1%)		0/697 (0%)
Haematochezia	1/694 (0.1%)		0/697 (0%)
Ileus Paralytic	1/694 (0.1%)		0/697 (0%)
Inguinal Hernia	1/694 (0.1%)		0/697 (0%)
Intestinal Obstruction	1/694 (0.1%)		0/697 (0%)
Lower Gastrointestinal Haemorrhage	1/694 (0.1%)		0/697 (0%)
Oesophageal Fistula	1/694 (0.1%)		0/697 (0%)
Oesophageal Stenosis	1/694 (0.1%)		0/697 (0%)
Proctitis Haemorrhagic	0/694 (0%)		1/697 (0.1%)
Upper Gastrointestinal Haemorrhage	0/694 (0%)		1/697 (0.1%)
General disorders
Pyrexia	13/694 (1.9%)		12/697 (1.7%)
Asthenia	2/694 (0.3%)		5/697 (0.7%)
Chest Pain	3/694 (0.4%)		0/697 (0%)
Malaise	3/694 (0.4%)		0/697 (0%)
Performance Status Decreased	3/694 (0.4%)		0/697 (0%)
Fatigue	1/694 (0.1%)		2/697 (0.3%)
General Physical Health Deterioration	1/694 (0.1%)		2/697 (0.3%)
Mucosal Inflammation	1/694 (0.1%)		2/697 (0.3%)
Chills	1/694 (0.1%)		0/697 (0%)
Death	0/694 (0%)		1/697 (0.1%)
Multi-Organ Failure	1/694 (0.1%)		1/697 (0.1%)
Pain	1/694 (0.1%)		0/697 (0%)
Sudden Death	1/694 (0.1%)		1/697 (0.1%)
Systemic Inflammatory Response Syndrome	0/694 (0%)		1/697 (0.1%)
Immune system disorders
Anaphylactic Shock	1/694 (0.1%)		2/697 (0.3%)
Drug Hypersensitivity	2/694 (0.3%)		1/697 (0.1%)
Infections and infestations
Pneumonia	33/694 (4.8%)		26/697 (3.7%)
Respiratory Tract Infection	5/694 (0.7%)		6/697 (0.9%)
Sepsis	5/694 (0.7%)		5/697 (0.7%)
Upper Respiratory Tract Infection	0/694 (0%)		5/697 (0.7%)
Gastroenteritis	4/694 (0.6%)		3/697 (0.4%)
Lung Infection	4/694 (0.6%)		2/697 (0.3%)
Urinary Tract Infection	4/694 (0.6%)		3/697 (0.4%)
Lower Respiratory Tract Infection	3/694 (0.4%)		1/697 (0.1%)
Septic Shock	3/694 (0.4%)		1/697 (0.1%)
Bacterial Infection	2/694 (0.3%)		0/697 (0%)
Bronchitis	0/694 (0%)		2/697 (0.3%)
Bronchopneumonia	0/694 (0%)		2/697 (0.3%)
Infection	0/694 (0%)		2/697 (0.3%)
Neutropenic Infection	1/694 (0.1%)		2/697 (0.3%)
Urosepsis	2/694 (0.3%)		0/697 (0%)
Appendicitis	1/694 (0.1%)		0/697 (0%)
Bacteraemia	1/694 (0.1%)		0/697 (0%)
Bacterial Sepsis	1/694 (0.1%)		0/697 (0%)
Bronchopulmonary Aspergillosis	1/694 (0.1%)		0/697 (0%)
Catheter Related Infection	0/694 (0%)		1/697 (0.1%)
Cellulitis	1/694 (0.1%)		0/697 (0%)
Central Line Infection	0/694 (0%)		1/697 (0.1%)
Diverticulitis	1/694 (0.1%)		1/697 (0.1%)
Empyema	1/694 (0.1%)		0/697 (0%)
Epiglottitis	0/694 (0%)		1/697 (0.1%)
Gastrointestinal Infection	1/694 (0.1%)		0/697 (0%)
Infective Exacerbation Of Chronic Obstructive Airways Disease	0/694 (0%)		1/697 (0.1%)
Infective Myositis	1/694 (0.1%)		0/697 (0%)
Lobar Pneumonia	1/694 (0.1%)		0/697 (0%)
Lung Abscess	1/694 (0.1%)		1/697 (0.1%)
Oesophageal Candidiasis	1/694 (0.1%)		0/697 (0%)
Perianal Abscess	0/694 (0%)		1/697 (0.1%)
Pneumocystis Jiroveci Pneumonia	1/694 (0.1%)		0/697 (0%)
Pneumonia Streptococcal	0/694 (0%)		1/697 (0.1%)
Pyothorax	1/694 (0.1%)		0/697 (0%)
Rash Pustular	1/694 (0.1%)		0/697 (0%)
Rectal Abscess	1/694 (0.1%)		0/697 (0%)
Respiratory Tract Infection Bacterial	0/694 (0%)		1/697 (0.1%)
Skin Bacterial Infection	1/694 (0.1%)		0/697 (0%)
Staphylococcal Infection	1/694 (0.1%)		0/697 (0%)
Tuberculosis	1/694 (0.1%)		0/697 (0%)
Injury, poisoning and procedural complications
Femur Fracture	2/694 (0.3%)		1/697 (0.1%)
Humerus Fracture	0/694 (0%)		2/697 (0.3%)
Brain Contusion	0/694 (0%)		1/697 (0.1%)
Facial Bones Fracture	0/694 (0%)		1/697 (0.1%)
Foot Fracture	1/694 (0.1%)		0/697 (0%)
Hip Fracture	1/694 (0.1%)		0/697 (0%)
Lower Limb Fracture	1/694 (0.1%)		0/697 (0%)
Multiple Fractures	0/694 (0%)		1/697 (0.1%)
Radiation Pneumonitis	1/694 (0.1%)		0/697 (0%)
Skin Laceration	0/694 (0%)		1/697 (0.1%)
Skull Fracture	0/694 (0%)		1/697 (0.1%)
Weight Decreased	0/694 (0%)		2/697 (0.3%)
White Blood Cell Count Decreased	0/694 (0%)		2/697 (0.3%)
Alanine Aminotransferase Increased	0/694 (0%)		1/697 (0.1%)
Aspartate Aminotransferase Increased	0/694 (0%)		1/697 (0.1%)
Blood Alkaline Phosphatase Increased	0/694 (0%)		1/697 (0.1%)
Blood Pressure Orthostatic Decreased	1/694 (0.1%)		0/697 (0%)
Electrocardiogram T Wave Abnormal	1/694 (0.1%)		0/697 (0%)
Neutrophil Count Decreased	0/694 (0%)		1/697 (0.1%)
Metabolism and nutrition disorders
Anorexia	3/694 (0.4%)		2/697 (0.3%)
Dehydration	1/694 (0.1%)		3/697 (0.4%)
Hyperkalaemia	1/694 (0.1%)		2/697 (0.3%)
Hypoglycaemia	2/694 (0.3%)		2/697 (0.3%)
Hyponatraemia	1/694 (0.1%)		2/697 (0.3%)
Diabetes Mellitus	1/694 (0.1%)		0/697 (0%)
Failure To Thrive	1/694 (0.1%)		0/697 (0%)
Hypercalcaemia	1/694 (0.1%)		1/697 (0.1%)
Hyperglycaemia	1/694 (0.1%)		1/697 (0.1%)
Hypokalaemia	1/694 (0.1%)		0/697 (0%)
Type 2 Diabetes Mellitus	0/694 (0%)		1/697 (0.1%)
Musculoskeletal and connective tissue disorders
Back Pain	2/694 (0.3%)		4/697 (0.6%)
Musculoskeletal Chest Pain	3/694 (0.4%)		4/697 (0.6%)
Arthralgia	0/694 (0%)		1/697 (0.1%)
Bone Pain	1/694 (0.1%)		1/697 (0.1%)
Flank Pain	0/694 (0%)		1/697 (0.1%)
Muscular Weakness	1/694 (0.1%)		1/697 (0.1%)
Musculoskeletal Pain	0/694 (0%)		1/697 (0.1%)
Myalgia	0/694 (0%)		1/697 (0.1%)
Pain In Extremity	1/694 (0.1%)		1/697 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour Pain	2/694 (0.3%)		2/697 (0.3%)
Metastatic Pain	1/694 (0.1%)		0/697 (0%)
Myelodysplastic Syndrome	1/694 (0.1%)		0/697 (0%)
Nervous system disorders
Convulsion	4/694 (0.6%)		1/697 (0.1%)
Dizziness	3/694 (0.4%)		4/697 (0.6%)
Headache	1/694 (0.1%)		3/697 (0.4%)
Loss Of Consciousness	3/694 (0.4%)		1/697 (0.1%)
Somnolence	0/694 (0%)		2/697 (0.3%)
Syncope	2/694 (0.3%)		2/697 (0.3%)
Altered State Of Consciousness	1/694 (0.1%)		0/697 (0%)
Ataxia	0/694 (0%)		1/697 (0.1%)
Brachial Plexopathy	0/694 (0%)		1/697 (0.1%)
Cauda Equina Syndrome	0/694 (0%)		1/697 (0.1%)
Cerebral Haemorrhage	0/694 (0%)		1/697 (0.1%)
Cerebral Infarction	1/694 (0.1%)		0/697 (0%)
Cerebral Ischaemia	1/694 (0.1%)		1/697 (0.1%)
Cerebrovascular Accident	1/694 (0.1%)		1/697 (0.1%)
Coma	0/694 (0%)		1/697 (0.1%)
Coma Hepatic	0/694 (0%)		1/697 (0.1%)
Dyskinesia	0/694 (0%)		1/697 (0.1%)
Hemiparesis	1/694 (0.1%)		0/697 (0%)
Ischaemic Stroke	1/694 (0.1%)		0/697 (0%)
Paraplegia	0/694 (0%)		1/697 (0.1%)
Peripheral Sensory Neuropathy	1/694 (0.1%)		0/697 (0%)
Polyneuropathy	1/694 (0.1%)		0/697 (0%)
Pyramidal Tract Syndrome	0/694 (0%)		1/697 (0.1%)
Spinal Cord Compression	1/694 (0.1%)		0/697 (0%)
Subarachnoid Haemorrhage	0/694 (0%)		1/697 (0.1%)
Psychiatric disorders
Mental Status Changes	2/694 (0.3%)		1/697 (0.1%)
Anxiety	0/694 (0%)		1/697 (0.1%)
Confusional State	1/694 (0.1%)		0/697 (0%)
Delirium	0/694 (0%)		1/697 (0.1%)
Psychotic Behaviour	1/694 (0.1%)		0/697 (0%)
Suicidal Ideation	0/694 (0%)		1/697 (0.1%)
Renal and urinary disorders
Dysuria	0/694 (0%)		2/697 (0.3%)
Renal Failure	2/694 (0.3%)		1/697 (0.1%)
Haematuria	1/694 (0.1%)		0/697 (0%)
Nephrolithiasis	0/694 (0%)		1/697 (0.1%)
Renal Failure Acute	1/694 (0.1%)		0/697 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	22/694 (3.2%)		21/697 (3%)
Interstitial Lung Disease	12/694 (1.7%)		6/697 (0.9%)
Pulmonary Embolism	2/694 (0.3%)		8/697 (1.1%)
Haemoptysis	5/694 (0.7%)		6/697 (0.9%)
Respiratory Failure	5/694 (0.7%)		6/697 (0.9%)
Pneumonitis	4/694 (0.6%)		5/697 (0.7%)
Pneumothorax	1/694 (0.1%)		5/697 (0.7%)
Pleural Effusion	4/694 (0.6%)		3/697 (0.4%)
Chronic Obstructive Pulmonary Disease	0/694 (0%)		3/697 (0.4%)
Cough	3/694 (0.4%)		0/697 (0%)
Aspiration	2/694 (0.3%)		0/697 (0%)
Epistaxis	0/694 (0%)		2/697 (0.3%)
Hypoxia	2/694 (0.3%)		1/697 (0.1%)
Pulmonary Haemorrhage	1/694 (0.1%)		2/697 (0.3%)
Respiratory Distress	1/694 (0.1%)		2/697 (0.3%)
Acute Respiratory Distress Syndrome	1/694 (0.1%)		0/697 (0%)
Asthma	0/694 (0%)		1/697 (0.1%)
Bronchospasm	1/694 (0.1%)		0/697 (0%)
Cryptogenic Organising Pneumonia	1/694 (0.1%)		0/697 (0%)
Diaphragmatic Rupture	0/694 (0%)		1/697 (0.1%)
Dyspnoea Exertional	0/694 (0%)		1/697 (0.1%)
Hydropneumothorax	1/694 (0.1%)		0/697 (0%)
Laryngeal Inflammation	1/694 (0.1%)		0/697 (0%)
Lung Infiltration	0/694 (0%)		1/697 (0.1%)
Pleurisy	0/694 (0%)		1/697 (0.1%)
Pneumonia Aspiration	1/694 (0.1%)		0/697 (0%)
Productive Cough	0/694 (0%)		1/697 (0.1%)
Pulmonary Alveolar Haemorrhage	0/694 (0%)		1/697 (0.1%)
Pulmonary Oedema	0/694 (0%)		1/697 (0.1%)
Respiratory Depression	1/694 (0.1%)		0/697 (0%)
Skin and subcutaneous tissue disorders
Rash	15/694 (2.2%)		1/697 (0.1%)
Photosensitivity Reaction	5/694 (0.7%)		0/697 (0%)
Toxic Epidermal Necrolysis	4/694 (0.6%)		0/697 (0%)
Dermatitis Exfoliative	3/694 (0.4%)		0/697 (0%)
Stevens-Johnson Syndrome	3/694 (0.4%)		0/697 (0%)
Drug Eruption	2/694 (0.3%)		0/697 (0%)
Erythema	2/694 (0.3%)		0/697 (0%)
Pruritus	2/694 (0.3%)		0/697 (0%)
Rash Erythematous	2/694 (0.3%)		0/697 (0%)
Toxic Skin Eruption	2/694 (0.3%)		0/697 (0%)
Dermatitis	1/694 (0.1%)		0/697 (0%)
Erythema Multiforme	1/694 (0.1%)		0/697 (0%)
Exfoliative Rash	1/694 (0.1%)		0/697 (0%)
Palmar-Plantar Erythrodysaesthesia Syndrome	1/694 (0.1%)		0/697 (0%)
Rash Maculo-Papular	1/694 (0.1%)		0/697 (0%)
Skin Toxicity	1/694 (0.1%)		0/697 (0%)
Telangiectasia	1/694 (0.1%)		0/697 (0%)
Vascular disorders
Deep Vein Thrombosis	1/694 (0.1%)		6/697 (0.9%)
Hypotension	5/694 (0.7%)		1/697 (0.1%)
Peripheral Arterial Occlusive Disease	1/694 (0.1%)		0/697 (0%)
Peripheral Ischaemia	1/694 (0.1%)		0/697 (0%)
Shock	0/694 (0%)		1/697 (0.1%)
Subclavian Vein Thrombosis	1/694 (0.1%)		0/697 (0%)
Superior Vena Caval Stenosis	1/694 (0.1%)		0/697 (0%)
Vasculitis	0/694 (0%)		1/697 (0.1%)
Vena Cava Thrombosis	0/694 (0%)		1/697 (0.1%)
Venous Thrombosis	1/694 (0.1%)		0/697 (0%)
Other (Not Including Serious) Adverse Events
	Vandetanib 100 mg Plus Docetaxel		Placebo Plus Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	637/694 (91.8%)		630/697 (90.4%)
Blood and lymphatic system disorders
Neutropenia	212/694 (30.5%)		174/697 (25%)
Leukopenia	125/694 (18%)		106/697 (15.2%)
Anaemia	68/694 (9.8%)		98/697 (14.1%)
Gastrointestinal disorders
Diarrhoea	284/694 (40.9%)		218/697 (31.3%)
Nausea	158/694 (22.8%)		221/697 (31.7%)
Vomiting	105/694 (15.1%)		141/697 (20.2%)
Constipation	119/694 (17.1%)		140/697 (20.1%)
Stomatitis	80/694 (11.5%)		80/697 (11.5%)
Abdominal Pain	41/694 (5.9%)		50/697 (7.2%)
Dyspepsia	37/694 (5.3%)		25/697 (3.6%)
Abdominal Pain Upper	30/694 (4.3%)		36/697 (5.2%)
General disorders
Fatigue	208/694 (30%)		214/697 (30.7%)
Pyrexia	127/694 (18.3%)		110/697 (15.8%)
Asthenia	105/694 (15.1%)		90/697 (12.9%)
Oedema Peripheral	49/694 (7.1%)		57/697 (8.2%)
Mucosal Inflammation	49/694 (7.1%)		38/697 (5.5%)
Infections and infestations
Nasopharyngitis	41/694 (5.9%)		37/697 (5.3%)
Weight Decreased	54/694 (7.8%)		41/697 (5.9%)
Metabolism and nutrition disorders
Anorexia	199/694 (28.7%)		204/697 (29.3%)
Musculoskeletal and connective tissue disorders
Myalgia	90/694 (13%)		78/697 (11.2%)
Back Pain	51/694 (7.3%)		62/697 (8.9%)
Arthralgia	61/694 (8.8%)		52/697 (7.5%)
Pain In Extremity	39/694 (5.6%)		31/697 (4.4%)
Musculoskeletal Pain	35/694 (5%)		30/697 (4.3%)
Nervous system disorders
Headache	58/694 (8.4%)		62/697 (8.9%)
Dizziness	43/694 (6.2%)		58/697 (8.3%)
Dysgeusia	40/694 (5.8%)		49/697 (7%)
Peripheral Sensory Neuropathy	42/694 (6.1%)		48/697 (6.9%)
Paraesthesia	42/694 (6.1%)		42/697 (6%)
Psychiatric disorders
Insomnia	95/694 (13.7%)		73/697 (10.5%)
Respiratory, thoracic and mediastinal disorders
Cough	130/694 (18.7%)		133/697 (19.1%)
Dyspnoea	102/694 (14.7%)		122/697 (17.5%)
Epistaxis	50/694 (7.2%)		27/697 (3.9%)
Haemoptysis	37/694 (5.3%)		45/697 (6.5%)
Dysphonia	41/694 (5.9%)		20/697 (2.9%)
Hiccups	30/694 (4.3%)		41/697 (5.9%)
Skin and subcutaneous tissue disorders
Rash	282/694 (40.6%)		166/697 (23.8%)
Alopecia	230/694 (33.1%)		240/697 (34.4%)
Pruritus	65/694 (9.4%)		42/697 (6%)
Nail Disorder	52/694 (7.5%)		46/697 (6.6%)
Dry Skin	45/694 (6.5%)		30/697 (4.3%)
Photosensitivity Reaction	42/694 (6.1%)		1/697 (0.1%)
Vascular disorders
Hypertension	41/694 (5.9%)		13/697 (1.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.