An Efficacy and Safety Study of Intetumumab (CNTO 95) in Participants With Metastatic Hormone Refractory Prostate Cancer

• Sponsor: Centocor, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00537381
• Collaborator: (none)
• Enrollment: 131
• Locations: 60
• Arms: 2
• Duration (Months): 30.1
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the effects of intetumumab when given in combination with docetaxel and prednisone to participants with metastatic (spread of cancer cells from one part of the body to another) hormone-refractory (not responding to treatment) prostate cancer (abnormal tissue that grows and spreads in the body until it kills).

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms	Drug: Docetaxel; Drug: Prednisone; Biological: Intetumumab; Drug: Placebo	Phase 2

Detailed Description

This is a multicenter (when more than one hospital or medical school team work on a medical research study), randomized (the study drug is assigned by chance), double-blind (neither physician nor participant knows the treatment that the participant receives) study of intetumumab in combination with docetaxel and prednisone for the first-line treatment of participants with metastatic hormone-refractory prostate cancer. There will be 2 study groups. One group will receive intetumumab in combination with docetaxel and prednisone (study treatment) and the other group will receive placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial) matching to intetumumab in combination with docetaxel and prednisone (control treatment). The duration of treatment will be 6 months. Participants who respond to treatment with stable disease or better will receive extended treatment until disease progression (disease worsening) or for an additional 6 months, whichever occurs first. Treatment can be further continued with the sponsor's discretion after receiving 6 months of extended treatment, if participant response to the treatment (with stable disease, partial response, or complete response). Participants who have confirmed progressive disease while receiving study treatment may have their treatment unblinded (participants will know the name of drug which was given to them), if they wish to be considered for alternative treatment. Participants who were receiving the control treatment will be considered to have completed the study treatment, and will have the option to receive alternative treatment. Alternative treatment will either be intetumumab along with docetaxel and prednisone or intetumumab alone. Participants' safety will be monitored throughout the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 131 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Multicenter, Phase 2 Study of a Human Monoclonal Antibody to Human av Integrins (CNTO 95) in Combination With Docetaxel for the First-Line Treatment of Subjects With Metastatic Hormone Refractory Prostate Cancer
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Docetaxel + Prednisone + Placebo Matching placebo as intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 milligram per square meter (mg/m^2) as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression.	Drug: Docetaxel; Docetaxel 75 mg/m^2 as intravenous infusion every 3 weeks.; Drug: Prednisone; Prednisone 5 mg orally twice daily.; Drug: Placebo; Placebo matching to intetumumab, as intravenous infusion every week for initial 6 weeks, then every 3 weeks.
Experimental: Docetaxel + Prednisone + Intetumumab Intetumumab 10 mg per kilogram (mg/kg) as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 mg/m^2 as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression.	Drug: Docetaxel; Docetaxel 75 mg/m^2 as intravenous infusion every 3 weeks.; Drug: Prednisone; Prednisone 5 mg orally twice daily.; Biological: Intetumumab; Intetumumab 10 mg/kg as intravenous infusion every week for initial 6 weeks, then every 3 weeks.; Other Names: CNTO 95

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) [Baseline up to 6 months after last dose of study treatment, assessed up to 551 days]

   The PFS was assessed as median number of days from baseline until the first documented sign of disease progression (increase in disease; radiographic, clinical, or both) or death due to any cause, whichever occurred earlier.

Secondary Outcome Measures

1. Number of Participants With Best Overall Response (OR) [Baseline up to 6 months after last dose of study treatment, assessed up to 551 days]

   Number of participants with best OR is based on assessment of confirmed complete response (CR) or confirmed partial response (PR). Confirmed CR is defined as disappearance of all target lesions. Confirmed PR is defined as greater than or equal to 30 percent decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD. Confirmed responses are those that persist on repeat imaging study greater than or equal to 4 weeks after initial documentation of response.

2. Number of Participants With Prostate Specific Antigen (PSA) Response [Baseline up to 6 months after last dose of study treatment or early withdrawal, assessed up to 601 days]

   The PSA response is defined as at least a 50 percent decrease in PSA below the baseline value, confirmed by a second PSA value greater than or equal to 6 weeks later. A participant was considered to be a PSA responder if and only if the response occurs prior to PSA progression (increase of at least 25 percent and an increase of 5 nanogram per milliliter from the lowest observed PSA value since initiation of treatment, to be confirmed greater than or equal to 3 weeks later).

3. Overall Survival [Baseline until death (up to 887 days)]

   Overall Survival is defined as the time from the date of randomization to death due to any cause. For participants who were alive at the time of analysis, overall survival was censored at the last contact date.

4. Percent Change From Baseline in 'C-telopeptide of Type I Collagen (CTx)' Marker Concentration [Baseline, Week 6, 7, 10 and 13]

   Percent change = marker concentration at time of measurement minus baseline value divided by baseline value multiplied by 100.

5. Percent Change From Baseline in 'N-telopeptide of Type I Collagen (NTx)' Marker Concentration [Baseline, Week 6, 7, 10 and 13]

   Percent change = marker concentration at time of measurement minus baseline value divided by baseline value multiplied by 100.

6. Percent Change From Baseline in 'Vascular Endothelial Growth Factor (VEGF)' Marker Concentration [Baseline, Week 6, 7, 10 and 13]

   Percent change = marker concentration at time of measurement minus baseline value divided by baseline value multiplied by 100.

Eligibility Criteria

Criteria

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

Inclusion Criteria

• Confirmed cancer of the prostate

• Evidence of metastatic disease

• Have a life expectancy greater than 12 weeks

• Have at least 4 weeks from previous major surgery to date of first study agent given

• Have progressive hormone-refractory disease after orchiectomy or gonadotropin-releasing hormone analog and/or antiandrogen treatment within 6 months prior to the first study agent administration Exclusion Criteria

• Have known Central Nervous System metastases (cancerous tumors that have spread to the brain from somewhere else in the body)

• Had prior systemic non-hormonal therapy for hormone refractory prostate cancer

• Have known Human Immunodeficiency Virus (HIV, a life-threatening infection which you can get from an infected person's blood or from having sex with an infected person) seropositivity or known hepatitis B or C infection

• Have planned major surgery during the study

• Have taken any over-the-counter (medicine that can be bought without a prescription) or herbal treatment for prostate cancer within 4 weeks prior to the first study treatment administration

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States
2		Los Angeles	California	United States
3		San Bernardino	California	United States
4		Wichita	Kansas	United States
5		Shreveport	Louisiana	United States
6		Charleston	South Carolina	United States
7		N Charleston	South Carolina	United States
8		Graz		Austria
9		Wels N/A		Austria
10		Wien		Austria
11		Antwerpen		Belgium
12		Brasschaat		Belgium
13		Brussel		Belgium
14		Doornik		Belgium
15		Haine-Saint-Paul, La Louviere		Belgium
16		Leuven		Belgium
17		Liÿge		Belgium
18		Ottignies		Belgium
19		Roeselare		Belgium
20		Wilrijk		Belgium
21		Aschaffenburg		Germany
22		Berlin		Germany
23		Freiburg		Germany
24		Kirchheim		Germany
25		Köln		Germany
26		Marburg		Germany
27		München		Germany
28		Tübingen		Germany
29		Ahmedabad		India
30		Bangalore		India
31		Chennai		India
32		Mumbai		India
33		New Delhi		India
34		Pune		India
35		Apeldoorn		Netherlands
36		Den Haag		Netherlands
37		Leiden		Netherlands
38		Maastricht		Netherlands
39		Nijmegen		Netherlands
40		Bydgoszcz		Poland
41		Gdansk		Poland
42		Inowroclaw		Poland
43		Koscierzyna		Poland
44		Lodz		Poland
45		Lublin		Poland
46		Ekaterinburg		Russian Federation
47		Moscow N/A		Russian Federation
48		Moscow Region		Russian Federation
49		Moscow		Russian Federation
50		St Petersburg		Russian Federation
51		St-Petersburg Leningrad		Russian Federation
52		Voronezh		Russian Federation
53		Yaroslavl		Russian Federation
54		Johannesburg Gauteng		South Africa
55		Pretoria Gauteng		South Africa
56		Pretoria		South Africa
57		Cambridge		United Kingdom
58		Leicester		United Kingdom
59		Lincoln		United Kingdom
60		London		United Kingdom

Sponsors and Collaborators

• Centocor, Inc.

Investigators

• Study Director: Centocor, Inc. Clinical Trial, Centocor, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Centocor, Inc.
• ClinicalTrials.gov Identifier: NCT00537381
• Other Study ID Numbers: CR013249; C1034T08; 2006-005766-39
• First Posted: Oct 1, 2007
• Last Update Posted: Jun 20, 2013
• Last Verified: Jun 1, 2013

• Keywords provided by Centocor, Inc.: Prostatic neoplasms; CNTO 95; Intetumumab; Docetaxel; Prednisone
• Additional relevant MeSH terms: Prostatic Neoplasms; Prednisone; Docetaxel; Intetumumab

Study Results

Participant Flow

Arm/Group Title	Docetaxel + Prednisone + Placebo	Docetaxel + Prednisone + Intetumumab
Arm/Group Description	Matching placebo as intravenous infusion (a fluid or a medicine delivered into a vein by way of a needle) every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 milligram per square meter (mg/m^2) as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression. Participants with disease progression at any time had option to crossover to alternative treatment with intetumumab alone or intetumumab in combination with docetaxel and prednisone.	Intetumumab 10 mg per kilogram (mg/kg) as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 mg/m^2 as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression.
Period Title: Overall Study
STARTED	65	66
COMPLETED	9	4
NOT COMPLETED	56	62

Baseline Characteristics

Arm/Group Title	Docetaxel + Prednisone + Placebo	Docetaxel + Prednisone + Intetumumab	Total
Arm/Group Description	Matching placebo as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 milligram per square meter (mg/m^2) as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression. Participants with disease progression at any time had option to crossover to alternative treatment with intetumumab alone or intetumumab in combination with docetaxel and prednisone.	Intetumumab 10 mg per kilogram (mg/kg) as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 mg/m^2 as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression.	Total of all reporting groups
Overall Participants	65	66	131
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	67.2 (8.74)	66.3 (7.51)	66.7 (8.13)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	65 100%	66 100%	131 100%
Region of Enrollment (participants) [Number]
AUSTRIA	3 4.6%	2 3%	5 3.8%
BELGIUM	10 15.4%	9 13.6%	19 14.5%
GERMANY	19 29.2%	14 21.2%	33 25.2%
INDIA	11 16.9%	10 15.2%	21 16%
NETHERLANDS	2 3.1%	5 7.6%	7 5.3%
POLAND	13 20%	10 15.2%	23 17.6%
RUSSIAN FEDERATION	4 6.2%	12 18.2%	16 12.2%
SOUTH AFRICA	1 1.5%	0 0%	1 0.8%
UNITED KINGDOM	1 1.5%	1 1.5%	2 1.5%
UNITED STATES	1 1.5%	3 4.5%	4 3.1%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS)
Description	The PFS was assessed as median number of days from baseline until the first documented sign of disease progression (increase in disease; radiographic, clinical, or both) or death due to any cause, whichever occurred earlier.
Time Frame	Baseline up to 6 months after last dose of study treatment, assessed up to 551 days

Outcome Measure Data

Analysis Population Description

Efficacy population included all participants randomly assigned to study treatment.

Arm/Group Title	Docetaxel + Prednisone + Placebo	Docetaxel + Prednisone + Intetumumab
Arm/Group Description	Matching placebo as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 milligram per square meter (mg/m^2) as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression. Participants with disease progression at any time had option to crossover to alternative treatment with intetumumab alone or intetumumab in combination with docetaxel and prednisone.	Intetumumab 10 mg per kilogram (mg/kg) as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 mg/m^2 as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression.
Measure Participants	65	66
Median (95% Confidence Interval) [Days]	336.0	232.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Docetaxel + Prednisone + Placebo, Docetaxel + Prednisone + Intetumumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.728
	Confidence Interval	(2-Sided) 95%; 1.112 to 2.686
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio and 95% confidence interval was estimated from a Cox proportional hazards model with treatment as the only explanatory factor.

2. Secondary Outcome

Title	Number of Participants With Best Overall Response (OR)
Description	Number of participants with best OR is based on assessment of confirmed complete response (CR) or confirmed partial response (PR). Confirmed CR is defined as disappearance of all target lesions. Confirmed PR is defined as greater than or equal to 30 percent decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD. Confirmed responses are those that persist on repeat imaging study greater than or equal to 4 weeks after initial documentation of response.
Time Frame	Baseline up to 6 months after last dose of study treatment, assessed up to 551 days

Outcome Measure Data

Analysis Population Description

Response evaluable population included participants who had target lesion or non-target lesion at baseline and received at least 1 study treatment and had at least 1 post-baseline response assessment or discontinued study treatment due to disease progression, or death.

Arm/Group Title	Docetaxel + Prednisone + Placebo	Docetaxel + Prednisone + Intetumumab
Arm/Group Description	Matching placebo as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 milligram per square meter (mg/m^2) as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression. Participants with disease progression at any time had option to crossover to alternative treatment with intetumumab alone or intetumumab in combination with docetaxel and prednisone.	Intetumumab 10 mg per kilogram (mg/kg) as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 mg/m^2 as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression.
Measure Participants	50	50
Complete Response	1 1.5%	0 0%
Partial Response	9 13.8%	8 12.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Docetaxel + Prednisone + Placebo, Docetaxel + Prednisone + Intetumumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.795
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Number of Participants With Prostate Specific Antigen (PSA) Response
Description	The PSA response is defined as at least a 50 percent decrease in PSA below the baseline value, confirmed by a second PSA value greater than or equal to 6 weeks later. A participant was considered to be a PSA responder if and only if the response occurs prior to PSA progression (increase of at least 25 percent and an increase of 5 nanogram per milliliter from the lowest observed PSA value since initiation of treatment, to be confirmed greater than or equal to 3 weeks later).
Time Frame	Baseline up to 6 months after last dose of study treatment or early withdrawal, assessed up to 601 days

Outcome Measure Data

Analysis Population Description

Included all participants randomly assigned to study treatment and had baseline PSA evaluation and at least two post-baseline evaluations that are at least 3 weeks apart.

Arm/Group Title	Docetaxel + Prednisone + Placebo	Docetaxel + Prednisone + Intetumumab
Arm/Group Description	Matching placebo as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 milligram per square meter (mg/m^2) as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression. Participants with disease progression at any time had option to crossover to alternative treatment with intetumumab alone or intetumumab in combination with docetaxel and prednisone.	Intetumumab 10 mg per kilogram (mg/kg) as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 mg/m^2 as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression.
Measure Participants	63	58
Number [Participants]	43 66.2%	27 40.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Docetaxel + Prednisone + Placebo, Docetaxel + Prednisone + Intetumumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.018
	Comments
	Method	Fisher Exact
	Comments

4. Secondary Outcome

Title	Overall Survival
Description	Overall Survival is defined as the time from the date of randomization to death due to any cause. For participants who were alive at the time of analysis, overall survival was censored at the last contact date.
Time Frame	Baseline until death (up to 887 days)

Outcome Measure Data

Analysis Population Description

Efficacy population included all participants randomly assigned to study treatment.

Arm/Group Title	Docetaxel + Prednisone + Placebo	Docetaxel + Prednisone + Intetumumab
Arm/Group Description	Matching placebo as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 milligram per square meter (mg/m^2) as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression. Participants with disease progression at any time had option to crossover to alternative treatment with intetumumab alone or intetumumab in combination with docetaxel and prednisone.	Intetumumab 10 mg per kilogram (mg/kg) as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 mg/m^2 as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression.
Measure Participants	65	66
Median (95% Confidence Interval) [Days]	626.0	522.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Docetaxel + Prednisone + Placebo, Docetaxel + Prednisone + Intetumumab
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.163
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.476
	Confidence Interval	(2-Sided) 95%; 0.853 to 2.522
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio and 95% confidence interval was estimated from a Cox proportional hazards model with treatment as the only explanatory factor.

5. Secondary Outcome

Title	Percent Change From Baseline in 'C-telopeptide of Type I Collagen (CTx)' Marker Concentration
Description	Percent change = marker concentration at time of measurement minus baseline value divided by baseline value multiplied by 100.
Time Frame	Baseline, Week 6, 7, 10 and 13

Outcome Measure Data

Analysis Population Description

The pharmacodynamic (PD) analysis set included all participants who received at least 1 dose of study treatment and had at least 1 PD measurement. Here 'n' signifies those participants evaluable for this measure at the specified time point for each arm group, respectively.

Arm/Group Title	Docetaxel + Prednisone + Placebo	Docetaxel + Prednisone + Intetumumab
Arm/Group Description	Matching placebo as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 milligram per square meter (mg/m^2) as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression. Participants with disease progression at any time had option to crossover to alternative treatment with intetumumab alone or intetumumab in combination with docetaxel and prednisone.	Intetumumab 10 mg per kilogram (mg/kg) as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 mg/m^2 as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression.
Measure Participants	11	65
Percent Change at Week 6 (n = 10, 48)	1.45 (51.019)	-30.81 (42.091)
Percent Change at Week 7 (n = 10, 54)	-11.58 (45.396)	-39.78 (32.437)
Percent Change at Week 10 (n = 11, 51)	2.39 (53.537)	-25.48 (122.178)
Percent Change at Week 13 (n = 11, 41)	5.22 (59.728)	-44.89 (40.941)

6. Secondary Outcome

Title	Percent Change From Baseline in 'N-telopeptide of Type I Collagen (NTx)' Marker Concentration
Description	Percent change = marker concentration at time of measurement minus baseline value divided by baseline value multiplied by 100.
Time Frame	Baseline, Week 6, 7, 10 and 13

Outcome Measure Data

Analysis Population Description

The PD analysis set included all participants who received at least 1 dose of study treatment and had at least 1 PD measurement. Here 'n' signifies those participants evaluable for this measure at the specified time point for each arm group, respectively.

Arm/Group Title	Docetaxel + Prednisone + Placebo	Docetaxel + Prednisone + Intetumumab
Arm/Group Description	Matching placebo as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 milligram per square meter (mg/m^2) as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression. Participants with disease progression at any time had option to crossover to alternative treatment with intetumumab alone or intetumumab in combination with docetaxel and prednisone.	Intetumumab 10 mg per kilogram (mg/kg) as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 mg/m^2 as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression.
Measure Participants	11	65
Percent Change at Week 6 (n = 10, 48)	-0.77 (37.584)	-21.37 (47.747)
Percent Change at Week 7 (n = 10, 54)	1.58 (40.651)	-23.44 (34.703)
Percent Change at Week 10 (n = 11, 51)	2.55 (46.433)	-21.71 (63.890)
Percent Change at Week 13 (n = 11, 40)	-3.87 (31.845)	-36.47 (25.701)

7. Secondary Outcome

Title	Percent Change From Baseline in 'Vascular Endothelial Growth Factor (VEGF)' Marker Concentration
Description	Percent change = marker concentration at time of measurement minus baseline value divided by baseline value multiplied by 100.
Time Frame	Baseline, Week 6, 7, 10 and 13

Outcome Measure Data

Analysis Population Description

The PD analysis set included all participants who received at least 1 dose of study treatment and had at least 1 PD measurement. Here 'n' signifies those participants evaluable for this measure at the specified time point for each arm group, respectively.

Arm/Group Title	Docetaxel + Prednisone + Placebo	Docetaxel + Prednisone + Intetumumab
Arm/Group Description	Matching placebo as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 milligram per square meter (mg/m^2) as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression. Participants with disease progression at any time had option to crossover to alternative treatment with intetumumab alone or intetumumab in combination with docetaxel and prednisone.	Intetumumab 10 mg per kilogram (mg/kg) as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 mg/m^2 as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression.
Measure Participants	11	65
Percent Change at Week 6 (n = 10, 48)	-10.00 (29.609)	-9.64 (34.229)
Percent Change at Week 7 (n = 10, 54)	-3.10 (24.465)	11.69 (41.338)
Percent Change at Week 10 (n = 11, 51)	3.96 (27.859)	32.11 (85.953)
Percent Change at Week 13 (n = 11, 41)	8.22 (32.622)	20.19 (55.565)

Adverse Events

Arm/Group Title	Docetaxel + Prednisone + Placebo		Docetaxel + Prednisone + Intetumumab		Docetaxel + Prednisone + Placebo/ Intetumumab		Docetaxel + Prednisone + Placebo/ D+ P + Intetumumab
Arm/Group Description	Matching placebo as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 milligram per square meter (mg/m^2) as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression. Participants with disease progression at any time had option to crossover to alternative treatment with intetumumab alone or intetumumab in combination with docetaxel and prednisone.		Intetumumab 10 mg per kilogram (mg/kg) as intravenous infusion every week for initial 6 weeks, then every 3 weeks; along with docetaxel 75 mg/m^2 as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily were administered till 6 months or disease progression.		Participants who initially received Docetaxel + Prednisone + Placebo until disease progression were switched their treatment to intetumumab alone (2 participants) and received intetumumab 10 mg/kg as intravenous infusion every 3 weeks till disease progression.		Participants who initially received Docetaxel + Prednisone + Placebo until disease progression were switched their treatment to Docetaxel (D) + Prednisone (P) + intetumumab (9 participants) and received intetumumab 10 mg/kg as intravenous infusion every 3 weeks; along with docetaxel 75 mg/m^2 as intravenous infusion every 3 weeks and prednisone 5 mg orally twice daily till disease progression.
All Cause Mortality
	Docetaxel + Prednisone + Placebo		Docetaxel + Prednisone + Intetumumab		Docetaxel + Prednisone + Placebo/ Intetumumab		Docetaxel + Prednisone + Placebo/ D+ P + Intetumumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Docetaxel + Prednisone + Placebo		Docetaxel + Prednisone + Intetumumab		Docetaxel + Prednisone + Placebo/ Intetumumab		Docetaxel + Prednisone + Placebo/ D+ P + Intetumumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/65 (35.4%)		24/66 (36.4%)		1/2 (50%)		4/9 (44.4%)
Blood and lymphatic system disorders
Anaemia	2/65 (3.1%)		2/66 (3%)		0/2 (0%)		0/9 (0%)
Febrile neutropenia	2/65 (3.1%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Haemorrhagic anaemia	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Leukopenia	0/65 (0%)		3/66 (4.5%)		0/2 (0%)		0/9 (0%)
Neutropenia	2/65 (3.1%)		2/66 (3%)		0/2 (0%)		0/9 (0%)
Cardiac disorders
Atrial fibrillation	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Cardiac disorder	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Cardiac failure	1/65 (1.5%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Ischaemic cardiomyopathy	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Myocardial infarction	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Gastrointestinal disorders
Abdominal pain	1/65 (1.5%)		3/66 (4.5%)		0/2 (0%)		1/9 (11.1%)
Diarrhoea	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		1/9 (11.1%)
Diverticular perforation	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Dysphagia	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Gastric ulcer	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Gastrointestinal haemorrhage	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Intestinal obstruction	0/65 (0%)		0/66 (0%)		0/2 (0%)		1/9 (11.1%)
Intestinal perforation	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Peritonitis	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Stomatitis	0/65 (0%)		2/66 (3%)		0/2 (0%)		0/9 (0%)
Upper gastrointestinal haemorrhage	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Vomiting	0/65 (0%)		0/66 (0%)		1/2 (50%)		0/9 (0%)
General disorders
Asthenia	2/65 (3.1%)		3/66 (4.5%)		0/2 (0%)		0/9 (0%)
Death	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Disease progression	0/65 (0%)		0/66 (0%)		0/2 (0%)		1/9 (11.1%)
Extravasation	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
General physical health deterioration	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Oedema	1/65 (1.5%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Pyrexia	3/65 (4.6%)		1/66 (1.5%)		1/2 (50%)		0/9 (0%)
Hepatobiliary disorders
Hepatic function abnormal	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Jaundice	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Infections and infestations
Bronchitis	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Cellulitis	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Necrotising fasciitis	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Oesophageal candidiasis	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Perirectal abscess	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Pneumonia	1/65 (1.5%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Sepsis	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Staphylococcal infection	0/65 (0%)		0/66 (0%)		1/2 (50%)		0/9 (0%)
Systemic candida	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Upper respiratory tract infection	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Urinary tract infection bacterial	0/65 (0%)		0/66 (0%)		0/2 (0%)		1/9 (11.1%)
Injury, poisoning and procedural complications
Alcohol poisoning	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Hip fracture	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Spinal cord injury	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Investigations
Coagulation time prolonged	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Weight decreased	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/65 (0%)		0/66 (0%)		1/2 (50%)		0/9 (0%)
Dehydration	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Hypercreatinaemia	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Pain in extremity	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone	0/65 (0%)		0/66 (0%)		0/2 (0%)		1/9 (11.1%)
Nervous system disorders
Balance disorder	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Dizziness	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Hypotonia	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Paraesthesia	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Paralysis	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Paraparesis	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Paraplegia	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Peripheral motor neuropathy	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Spinal cord compression	0/65 (0%)		3/66 (4.5%)		0/2 (0%)		0/9 (0%)
Syncope	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Renal and urinary disorders
Haematuria	2/65 (3.1%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Renal failure acute	1/65 (1.5%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Urinary retention	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		1/9 (11.1%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Cough	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Dyspnoea	2/65 (3.1%)		1/66 (1.5%)		1/2 (50%)		0/9 (0%)
Epistaxis	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Pulmonary embolism	2/65 (3.1%)		2/66 (3%)		0/2 (0%)		0/9 (0%)
Surgical and medical procedures
Pneumatic compression therapy	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Vascular disorders
Aneurysm	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Deep vein thrombosis	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Hypotension	2/65 (3.1%)		0/66 (0%)		0/2 (0%)		0/9 (0%)
Thrombosis	0/65 (0%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Docetaxel + Prednisone + Placebo		Docetaxel + Prednisone + Intetumumab		Docetaxel + Prednisone + Placebo/ Intetumumab		Docetaxel + Prednisone + Placebo/ D+ P + Intetumumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	59/65 (90.8%)		59/66 (89.4%)		2/2 (100%)		6/9 (66.7%)
Blood and lymphatic system disorders
Anaemia	12/65 (18.5%)		9/66 (13.6%)		1/2 (50%)		0/9 (0%)
Leukopenia	22/65 (33.8%)		16/66 (24.2%)		0/2 (0%)		1/9 (11.1%)
Neutropenia	21/65 (32.3%)		14/66 (21.2%)		0/2 (0%)		1/9 (11.1%)
Eye disorders
Dry eye	4/65 (6.2%)		3/66 (4.5%)		0/2 (0%)		0/9 (0%)
Keratoconjunctivitis sicca	5/65 (7.7%)		2/66 (3%)		0/2 (0%)		0/9 (0%)
Lacrimation increased	8/65 (12.3%)		7/66 (10.6%)		0/2 (0%)		2/9 (22.2%)
Ocular hyperaemia	1/65 (1.5%)		4/66 (6.1%)		0/2 (0%)		0/9 (0%)
Ocular hypertension	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		1/9 (11.1%)
Photophobia	0/65 (0%)		4/66 (6.1%)		0/2 (0%)		0/9 (0%)
Vision blurred	4/65 (6.2%)		3/66 (4.5%)		0/2 (0%)		0/9 (0%)
Gastrointestinal disorders
Abdominal pain	2/65 (3.1%)		2/66 (3%)		0/2 (0%)		1/9 (11.1%)
Colitis	0/65 (0%)		0/66 (0%)		0/2 (0%)		1/9 (11.1%)
Constipation	13/65 (20%)		9/66 (13.6%)		1/2 (50%)		2/9 (22.2%)
Diarrhoea	22/65 (33.8%)		18/66 (27.3%)		0/2 (0%)		2/9 (22.2%)
Gastritis	4/65 (6.2%)		3/66 (4.5%)		0/2 (0%)		0/9 (0%)
Nausea	17/65 (26.2%)		18/66 (27.3%)		1/2 (50%)		3/9 (33.3%)
Oesophagitis	1/65 (1.5%)		0/66 (0%)		0/2 (0%)		1/9 (11.1%)
Stomatitis	9/65 (13.8%)		3/66 (4.5%)		0/2 (0%)		0/9 (0%)
Vomiting	10/65 (15.4%)		6/66 (9.1%)		1/2 (50%)		0/9 (0%)
General disorders
Asthenia	16/65 (24.6%)		15/66 (22.7%)		1/2 (50%)		0/9 (0%)
Fatigue	17/65 (26.2%)		17/66 (25.8%)		0/2 (0%)		2/9 (22.2%)
Hypothermia	4/65 (6.2%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Mucosal inflammation	4/65 (6.2%)		2/66 (3%)		0/2 (0%)		0/9 (0%)
Oedema peripheral	7/65 (10.8%)		8/66 (12.1%)		0/2 (0%)		0/9 (0%)
Pain	5/65 (7.7%)		1/66 (1.5%)		0/2 (0%)		0/9 (0%)
Pyrexia	10/65 (15.4%)		13/66 (19.7%)		0/2 (0%)		0/9 (0%)
Hepatobiliary disorders
Hepatic function abnormal	6/65 (9.2%)		3/66 (4.5%)		0/2 (0%)		1/9 (11.1%)
Infections and infestations
Bronchitis	1/65 (1.5%)		0/66 (0%)		1/2 (50%)		0/9 (0%)
Moraxella infection	0/65 (0%)		0/66 (0%)		1/2 (50%)		0/9 (0%)
Nasopharyngitis	4/65 (6.2%)		5/66 (7.6%)		0/2 (0%)		1/9 (11.1%)
Rhinitis	1/65 (1.5%)		0/66 (0%)		1/2 (50%)		0/9 (0%)
Urinary tract infection	5/65 (7.7%)		2/66 (3%)		1/2 (50%)		1/9 (11.1%)
Metabolism and nutrition disorders
Decreased appetite	13/65 (20%)		9/66 (13.6%)		1/2 (50%)		1/9 (11.1%)
Enzyme abnormality	4/65 (6.2%)		5/66 (7.6%)		0/2 (0%)		0/9 (0%)
Hyperglycaemia	9/65 (13.8%)		9/66 (13.6%)		0/2 (0%)		0/9 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/65 (10.8%)		5/66 (7.6%)		0/2 (0%)		1/9 (11.1%)
Back pain	9/65 (13.8%)		4/66 (6.1%)		1/2 (50%)		2/9 (22.2%)
Bone pain	6/65 (9.2%)		3/66 (4.5%)		1/2 (50%)		1/9 (11.1%)
Musculoskeletal pain	3/65 (4.6%)		5/66 (7.6%)		0/2 (0%)		0/9 (0%)
Myalgia	8/65 (12.3%)		3/66 (4.5%)		0/2 (0%)		2/9 (22.2%)
Myositis	0/65 (0%)		0/66 (0%)		0/2 (0%)		1/9 (11.1%)
Pain in extremity	7/65 (10.8%)		7/66 (10.6%)		0/2 (0%)		0/9 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	1/65 (1.5%)		1/66 (1.5%)		0/2 (0%)		1/9 (11.1%)
Nervous system disorders
Dizziness	7/65 (10.8%)		6/66 (9.1%)		0/2 (0%)		0/9 (0%)
Dysgeusia	15/65 (23.1%)		13/66 (19.7%)		0/2 (0%)		1/9 (11.1%)
Headache	9/65 (13.8%)		13/66 (19.7%)		0/2 (0%)		0/9 (0%)
Neuropathy peripheral	4/65 (6.2%)		2/66 (3%)		0/2 (0%)		0/9 (0%)
Paraesthesia	10/65 (15.4%)		11/66 (16.7%)		0/2 (0%)		1/9 (11.1%)
Paresis	0/65 (0%)		0/66 (0%)		1/2 (50%)		0/9 (0%)
Peripheral sensory neuropathy	11/65 (16.9%)		9/66 (13.6%)		0/2 (0%)		0/9 (0%)
Psychiatric disorders
Depression	0/65 (0%)		1/66 (1.5%)		1/2 (50%)		0/9 (0%)
Insomnia	2/65 (3.1%)		7/66 (10.6%)		1/2 (50%)		0/9 (0%)
Renal and urinary disorders
Haematuria	4/65 (6.2%)		8/66 (12.1%)		1/2 (50%)		2/9 (22.2%)
Proteinuria	4/65 (6.2%)		1/66 (1.5%)		0/2 (0%)		1/9 (11.1%)
Respiratory, thoracic and mediastinal disorders
Cough	3/65 (4.6%)		4/66 (6.1%)		1/2 (50%)		1/9 (11.1%)
Dyspnoea	5/65 (7.7%)		4/66 (6.1%)		1/2 (50%)		0/9 (0%)
Epistaxis	8/65 (12.3%)		9/66 (13.6%)		0/2 (0%)		0/9 (0%)
Sputum increased	0/65 (0%)		0/66 (0%)		1/2 (50%)		0/9 (0%)
Skin and subcutaneous tissue disorders
Alopecia	28/65 (43.1%)		17/66 (25.8%)		0/2 (0%)		0/9 (0%)
Dry skin	1/65 (1.5%)		2/66 (3%)		1/2 (50%)		0/9 (0%)
Erythema	9/65 (13.8%)		7/66 (10.6%)		1/2 (50%)		0/9 (0%)
Nail disorder	12/65 (18.5%)		7/66 (10.6%)		0/2 (0%)		0/9 (0%)
Onychomadesis	0/65 (0%)		0/66 (0%)		0/2 (0%)		1/9 (11.1%)
Rash	6/65 (9.2%)		3/66 (4.5%)		0/2 (0%)		0/9 (0%)
Vascular disorders
Hypertension	5/65 (7.7%)		2/66 (3%)		0/2 (0%)		0/9 (0%)

Limitations/Caveats

Treatment with intetumumab/placebo was permanently discontinued after a planned, preliminary review of interim analysis data. Therefore, study treatment with intetumumab was not completed for some participants.

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Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.