A Proof of Concept Study of Maintenance Therapy With Tasquinimod in Patients With Metastatic Castrate-resistant Prostate Cancer Who Are Not Progressing After a First Line Docetaxel Based Chemotherapy

• ClinicalTrials.gov Identifier: NCT01732549
• Recruitment Status: Terminated
• First Posted: November 26, 2012
• Results First Posted: October 3, 2016
• Last Update Posted: November 22, 2019
• Sponsor: Ipsen
• Information provided by (Responsible Party): Ipsen

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Metastatic Castrate Resistant Prostate Cancer
• Interventions: Drug: Tasquinimod; Drug: Placebo
• Enrollment: 144

Participant Flow

Recruitment Details	The study was performed as a multicentre study at 51 investigational sites (of which 44 randomised patients) in Belgium, Czech Republic, Denmark, France, Germany, Hungary, Italy, Lithuania, Poland, Spain and United Kingdom (UK)
Pre-assignment Details	A total of 219 patients were screened and 144 patients were randomised.

Arm/Group Title	Tasquinimod	Placebo
Arm/Group Description	1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression. Tasquinimod: Patients received initially an oral dose of 0.25 mg/day of tasquinimod, starting on Day 1, for at least 2 weeks. Once tolerability of the 0.25 mg/day dose was established, patients received a dose increase to 0.5 mg/day for at least 2 weeks, and then increased to 1 mg/day of study treatment. Patients showing poor tolerability for the escalated doses of tasquinimod were allowed to continue study treatment at the highest individually tolerated dose	1 capsule daily, taken orally with water and food until disease progression Placebo: Patients received Placebo capsules (identical to tasquinimod capsules) to be taken orally once a day with water and food
Period Title: Overall Study
Started	71	73
Ongoing in Treatment Period:Data Cut-off	12	12
Withdrawn During Treatment:Data Cut-off	59 [1]	61 [2]
Ongoing Treatment Period:Final Analysis	0	0
Withdrawn During Treatment:Final Analysi	71	73
Completed	0	0
Not Completed	71	73
Reason Not Completed
Adverse Event	13	3
Consent withdrawn	13	6
Disease progression	37	50
Other	8	14
[1] Withdrawn during treatment period 59 (AE 13, Consent withdrawn 13, Disease progression 31, Other 2); [2] Withdrawn during treatment period 61 (AE 3, Consent withdrawn 6, Disease progression 46, Other 6)

Baseline Characteristics

Arm/Group Title		Tasquinimod	Placebo	Total
Arm/Group Description		1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression. Tasquinimod: Patients received initially an oral dose of 0.25 mg/day of tasquinimod, starting on Day 1, for at least 2 weeks. Once tolerability of the 0.25 mg/day dose was established, patients received a dose increase to 0.5 mg/day for at least 2 weeks, and then increased to 1 mg/day of study treatment. Patients showing poor tolerability for the escalated doses of tasquinimod were allowed to continue study treatment at the highest individually tolerated dose	1 capsule daily, taken orally with water and food until disease progression Placebo: Patients received Placebo capsules (identical to tasquinimod capsules) to be taken orally once a day with water and food	Total of all reporting groups
Overall Number of Baseline Participants		71	73	144
Baseline Analysis Population Description		ITT population: All randomised patients. Patients were allocated to the treatment they were randomised to. Patients randomised that have been actually dead before randomisation were not retained in the intention to treat (ITT) population
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	71 participants	73 participants	144 participants
		69.6 (7.18)	69.6 (5.57)	69.6 (6.39)
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	71 participants	73 participants	144 participants
18 to ≤ 65 years		18	17	35
66 to ≤ 75 years		40	45	85
> 75 years		13	11	24
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	71 participants	73 participants	144 participants
	Female	0 0.0%	0 0.0%	0 0.0%
	Male	71 100.0%	73 100.0%	144 100.0%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	71 participants	73 participants	144 participants
Black/African American		0	1	1
Caucasian/White		52	58	110
Multiple Race		1	0	1
Missing		18	14	32
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	71 participants	73 participants	144 participants
Czech Republic		5	1	6
Belgium		5	6	11
Hungary		2	2	4
Denmark		6	13	19
Poland		4	3	7
Italy		9	5	14
United Kingdom		8	6	14
France		17	14	31
Lithuania		7	10	17
Germany		3	3	6
Spain		5	10	15
Weight; Mean (Standard Deviation); Unit of measure: Kg
	Number Analyzed	71 participants	73 participants	144 participants
		83.7 (12.57)	83.4 (15.09)	83.6 (13.86)
BMI; Mean (Standard Deviation); Unit of measure: Kg/m^2
	Number Analyzed	71 participants	73 participants	144 participants
		27.67 (3.543)	28.01 (4.399)	27.84 (3.987)
Ethnicity; Measure Type: Number; Unit of measure: Participants	Number Analyzed	71 participants	73 participants	144 participants
Hispanic or Latino		2	4	6
Not Hispanic or Latino		52	55	107
Missing		17	14	31
ECOG Performance Status Score [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	71 participants	73 participants	144 participants
0 (Normal Activity)		39	31	70
1 (Restricted Activity)		32	38	70
Missing		0	4	4
		[1] Measure Description: Eastern Co-operative Oncology Group (ECOG) Score: 0=Fully active, able to carry on all pre-disease performance without restriction, 1=Restricted in physically strenuous activity, but ambulatory & able to carry out work of a light or sedentary nature, e.g. light house work, office work, 2=Ambulatory & capable of all self-care but unable to carry out any work activities. Up & about more than 50% of waking hours, 3=Capable of limited self-care,confined to bed or chair more than 50% of waking hours, 4=Completely disabled. Cannot carry on any self care. Totally confined to bed or chair, 5=Dead
Region; Measure Type: Number; Unit of measure: Participants	Number Analyzed	71 participants	73 participants	144 participants
Eastern Europe		18	16	34
Western Europe		53	57	110

Outcome Measures

1. Primary Outcome

Title	Time to Radiological Progression Free Survival [PFS]
Description	The time from the date of randomisation to the date of radiological progression or death due to any cause. Radiological progression was defined - Using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue lesions (Eisenhauer, EJC 2009), as at least a 20% relative and a 5 mm absolute increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded on study (including Screening or the appearance of one or more new lesions) for target Lesions. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions - Using Prostate Cancer Clinical Working Group in March 2008 (PCWG2) criteria for bone lesions (Scher, JCO 2008). Progression was defined as appearance of 2 or more bone lesions.
Time Frame	Every 8 weeks until disease progression documentation (approximately up to 2.5 years)

Outcome Measure Data

Analysis Population Description

Intention to treat (ITT) Population

Arm/Group Title	Tasquinimod	Placebo
Arm/Group Description:	1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression.	1 capsule daily, taken orally with water and food until disease progression
Overall Number of Participants Analyzed	71	73
Median (90% Confidence Interval); Unit of Measure: weeks
	31.7; (24.3 to 53.7)	22.7; (16.1 to 25.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasquinimod, Placebo
	Comments	Stratified[a]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.0315
	Comments	Log-rank test adjusting for presence (or absence) of visceral metastases, opioid analgesic use and region (Eastern Europe, Western Europe). Two-sided p-value.
	Method	Log Rank
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tasquinimod, Placebo
	Comments	Unstratified[b]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.0344
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]

2. Secondary Outcome

Title	Overall Survival Based on Number of Subjects Who Died
Description	Overall survival is defined as the time from randomisation to death due to any cause. The number of participants who died is presented since the Median was not reached for this assessment. Tasquinimod: Patients censored = 63, Patients at risk (t=0) = 71 Placebo: Patients censored = 67, Patients at risk (t=0) = 73
Time Frame	Every 3 months after study treatment stop until death (approximately up to 2.5 years)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Tasquinimod	Placebo
Arm/Group Description:	1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression	1 capsule daily, taken orally with water and food until disease progression
Overall Number of Participants Analyzed	71	73
Measure Type: Number; Unit of Measure: participants
	8	6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasquinimod, Placebo
	Comments	Stratified[a]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.4430
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Adjusting for presence (or absence) of visceral metastases, opioid analgesic use and region (Eastern Europe, Western Europe). One-sided p-value

3. Secondary Outcome

Title	Time to Progression Free Survival [PFS] on Next-line Therapy (PFS 2)
Description	The time from the date of randomisation to the date of radiological progression free survival [PFS] on next-line therapy (PFS 2) or death due to any cause. Radiological progression was defined - Using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for soft tissue lesions (Eisenhauer, EJC 2009), as at least a 20% relative and a 5 mm absolute increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded on study (including Screening or the appearance of one or more new lesions) for target Lesions. Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions - Using Prostate Cancer Clinical Working Group in March 2008 (PCWG2) criteria for bone lesions (Scher, JCO 2008). Progression was defined as appearance of 2 or more bone lesions.
Time Frame	Every 3 months after study treatment stop (follow-up) until progression under the next line therapy (approximately up to 2.5 years)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Tasquinimod	Placebo
Arm/Group Description:	1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression	1 capsule daily, taken orally with water and food until disease progression
Overall Number of Participants Analyzed	71	73
Median (90% Confidence Interval); Unit of Measure: weeks
	19.3; (7.1 to 30.7)	24.1 [1]; (12.6 to NA)

[1]

The data for this maximum confidence interval (CI) is not evaluable (NE), listed as Not Available (NA).

Patients censored = 44 Patients at risk (t=0) = 47

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasquinimod, Placebo
	Comments	Stratified[a]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.5219
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Adjusting for presence (or absence) of visceral metastases, opioid analgesic use and region (Eastern Europe, Western Europe). One-sided p-value

4. Secondary Outcome

Title	Symptomatic PFS Based on Number of Subjects Who Had Symptomatic Progression or Death
Description	Symptomatic PFS is defined as the time from the date of randomisation to the date of symptomatic progression or death due to prostate cancer, whichever occurs first [symptomatic progression as assessed by Brief Pain Inventory (BPI) and analgesic use]. Symptomatic progression was defined by the occurrence of pain with documented disease, skeleton related adverse events. The median symptomatic PFS for placebo and tasquinimod groups was not reached. Tasquinimod: Patients censored = 48, Patients at risk (t=0) = 71 Placebo: Patients censored = 54, Patients at risk (t=0) = 73
Time Frame	Every 8 weeks until symptomatic or radiological progression documentation (approximately up to 2.5 years)

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Tasquinimod	Placebo
Arm/Group Description:	1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression.	1 capsule daily, taken orally with water and food until disease progression
Overall Number of Participants Analyzed	71	73
Measure Type: Number; Unit of Measure: participants
	23	19

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasquinimod, Placebo
	Comments	Stratified[a]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.5442
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Adjusting for presence (or absence) of visceral metastases, opioid analgesic use and region (Eastern Europe, Western Europe). One-sided p-value

5. Secondary Outcome

Title	Time to Further Anticancer Treatment for Prostate Cancer
Description	Time from randomisation to further treatment for prostate cancer
Time Frame	Every 3 months after study treatment stop until further anticancer therapy for prostate cancer (approximately up to 2.5 years)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Tasquinimod	Placebo
Arm/Group Description:	1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression.	1 capsule daily, taken orally with water and food until disease progression
Overall Number of Participants Analyzed	71	73
Median (90% Confidence Interval); Unit of Measure: weeks
	42.3; (32.0 to 58.0)	29.0; (23.1 to 39.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasquinimod, Placebo
	Comments	Stratified[a]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.1120
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Adjusting for presence (or absence) of visceral metastases, opioid analgesic use and region (Eastern Europe, Western Europe). One-sided p-value

6. Secondary Outcome

Title	Time to Deterioration in Functional Assessment of Cancer Therapy - Prostate (FACT-P)
Description	End of Study visit (within 14 days of last dose of study treatment) Impact of tasquinimod on health related quality of life (QoL) - Analysis of time to deterioration in FACT-P The FACT-P measurement system is a validated collection of health related quality of life (HRQOL) questionnaires used to assess HRQOL in men with prostate cancer. It is appropriate for use with patients with any form of cancer and extensions of it have been used and validated in other chronic illness condition. The FACT-P is a self-administered 39-item scale comprising five domains: physical well-being, social/family well-being, functional well-being, emotional well-being and additional concerns. The individual subscale scores range from 0 to a high between 24 and 48 and the total score ranges between 0 and 156, with higher scores representing better Quality of Life (QoL)
Time Frame	Up to End of Study visit (approximately up to 2.5 years)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Tasquinimod	Placebo
Arm/Group Description:	1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression.	1 capsule daily, taken orally with water and food until disease progression
Overall Number of Participants Analyzed	71	73
Median (90% Confidence Interval); Unit of Measure: weeks
	8.1; (8.1 to 13.1)	15.7; (10.6 to 16.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasquinimod, Placebo
	Comments	Stratified[a]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	=0.2491
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Adjusting for presence (or absence) of visceral metastases, opioid analgesic use (or not) & region (Eastern Europe, Western Europe). One-sided p-value

7. Secondary Outcome

Title	Change From Baseline of EuroQol-5 Dimension QoL Instrument (EQ-5D) VAS Score
Description	Baseline is defined as last measurement collected prior to the first dose of study drug. End of Study visit (within 14 days of last dose of study treatment) The EQ-5D, a 5-item scale useful in health resource utilisation and cost comparisons between treatment groups designed for self-completion by patients consists of two pages [EQ-5 descriptive system and EQ Visual Analogue Scale(VAS)]. The EQ-5 descriptive system comprises five dimensions: mobility, self care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, severe problems. The EQ-VAS records the respondent's self-rated health on a vertical VAS. The respondents are asked to mark health status on the day of the interview on a 10cm vertical scale with end points of 0 to100. There are notes at the both ends of the scale that the bottom rate(0) corresponds to "the worst health you can imagine", and the highest rate(100) corresponds to "the best health you can imagine"
Time Frame	Baseline and End-of-study Visit (approximately up to 2.5 years)

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	Tasquinimod	Placebo
Arm/Group Description:	1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression.	1 capsule daily, taken orally with water and food until disease progression
Overall Number of Participants Analyzed	39	50
Median (Inter-Quartile Range); Unit of Measure: Score on scale
	-9.0; (-74 to 63)	-3.5; (-55 to 30)

8. Secondary Outcome

Title	Safety Profile of Tasquinimod
Description	Number of subjects reporting adverse events
Time Frame	At regular intervals during the study treatment period and every 3 months during the follow-up until death (approximately up to 2.5 years)

Outcome Measure Data

Analysis Population Description

Safety Population: All patients who received at least one dose of study treatment. Patients were allocated to the treatment they actually received

Arm/Group Title	Tasquinimod	Placebo
Arm/Group Description:	1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression.	1 capsule daily, taken orally with water and food until disease progression
Overall Number of Participants Analyzed	71	70
Measure Type: Number; Unit of Measure: participants
Any Treatment Emergent Adverse Event (TEAEs)	69	66
Intensity of TEAEs [Grade 3-5 (severe)]	36	19
Intensity of TEAEs [Grade 5]	1	3
Intensity of TEAEs [Grade 4]	3	2
Intensity of TEAEs [Grade 3]	32	14
Intensity of TEAEs [Grade 2 (moderate)]	28	28
Intensity of TEAEs [Grade 1 (mild)]	5	19
Causality of TEAEs [Drug Related]	54	38
Causality of TEAEs [Not Drug Related]	15	28
TEAEs Leading to Drug Withdrawal	12	3
TEAEs leading to Dose Reduction	16	2
TEAEs leading to Drug Interruption	33	12
TEAEs Leading to Death	1	0
Serious Adverse Event (SAEs)	24	16
Drug Related SAEs	6	2

Adverse Events

Time Frame	At regular intervals during the study treatment period and every 3 months during the follow-up until death (approximately up to 2.5 years)
Adverse Event Reporting Description	Non-SAE details: A summary of common (incidence >5%) TEAEs is presented
Arm/Group Title	Tasquinimod	Placebo
Arm/Group Description	1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg and then to 1 mg per day) until disease progression. Tasquinimod: Patients received initially an oral dose of 0.25 mg/day of tasquinimod, starting on Day 1, for at least 2 weeks. Once tolerability of the 0.25 mg/day dose was established, patients received a dose increase to 0.5 mg/day for at least 2 weeks, and then increased to 1 mg/day of study treatment. Patients showing poor tolerability for the escalated doses of tasquinimod were allowed to continue study treatment at the highest individually tolerated dose	1 capsule daily, taken orally with water and food until disease progression Placebo: Patients received Placebo capsules (identical to tasquinimod capsules) to be taken orally once a day with water and food
All-Cause Mortality
	Tasquinimod	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Tasquinimod	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	24/71 (33.80%)	16/70 (22.86%)
Blood and lymphatic system disorders
Anaemia † 1	1/71 (1.41%)	0/70 (0.00%)
Cardiac disorders
Myocardial ischaemia † 1	1/71 (1.41%)	1/70 (1.43%)
Arteriosclerosis coronary artery † 1	1/71 (1.41%)	0/70 (0.00%)
Cardiac failure † 1	1/71 (1.41%)	0/70 (0.00%)
Myocardial infarction † 1	1/71 (1.41%)	0/70 (0.00%)
Pericarditis † 1	0/71 (0.00%)	1/70 (1.43%)
Eye disorders
Dacryostenosis acquired † 1	0/71 (0.00%)	1/70 (1.43%)
Gastrointestinal disorders
Vomiting † 1	2/71 (2.82%)	1/70 (1.43%)
Ileus † 1	1/71 (1.41%)	1/70 (1.43%)
Nausea † 1	1/71 (1.41%)	1/70 (1.43%)
Abdominal pain † 1	0/71 (0.00%)	1/70 (1.43%)
Colitis † 1	1/71 (1.41%)	0/70 (0.00%)
Constipation † 1	0/71 (0.00%)	1/70 (1.43%)
Large intestine perforation † 1	1/71 (1.41%)	0/70 (0.00%)
Proctitis † 1	1/71 (1.41%)	0/70 (0.00%)
General disorders
Fatigue † 1	1/71 (1.41%)	1/70 (1.43%)
Disease progression † 1	1/71 (1.41%)	0/70 (0.00%)
General physical health deterioration † 1	0/71 (0.00%)	1/70 (1.43%)
Pyrexia † 1	1/71 (1.41%)	0/70 (0.00%)
Hepatobiliary disorders
Biliary cyst † 1	1/71 (1.41%)	0/70 (0.00%)
Infections and infestations
Urinary tract infection † 1	1/71 (1.41%)	1/70 (1.43%)
Appendicitis perforated † 1	0/71 (0.00%)	1/70 (1.43%)
Bronchitis † 1	0/71 (0.00%)	1/70 (1.43%)
Erysipelas † 1	0/71 (0.00%)	1/70 (1.43%)
Pyelonephritis acute † 1	1/71 (1.41%)	0/70 (0.00%)
Injury, poisoning and procedural complications
Facial bones fracture † 1	0/71 (0.00%)	1/70 (1.43%)
Fall † 1	0/71 (0.00%)	1/70 (1.43%)
Laceration † 1	0/71 (0.00%)	1/70 (1.43%)
Spinal fracture † 1	1/71 (1.41%)	0/70 (0.00%)
Investigations
Blood creatinine increased † 1	1/71 (1.41%)	0/70 (0.00%)
Metabolism and nutrition disorders
Decreased appetite † 1	2/71 (2.82%)	0/70 (0.00%)
Fluid retention † 1	1/71 (1.41%)	0/70 (0.00%)
Musculoskeletal and connective tissue disorders
Chondrocalcinosis † 1	1/71 (1.41%)	0/70 (0.00%)
Lumbar spinal stenosis † 1	1/71 (1.41%)	0/70 (0.00%)
Muscular weakness † 1	1/71 (1.41%)	0/70 (0.00%)
Pain in extremity † 1	1/71 (1.41%)	0/70 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma † 1	0/71 (0.00%)	1/70 (1.43%)
Metastases to central nervous system † 1	0/71 (0.00%)	1/70 (1.43%)
Nervous system disorders
Headache † 1	1/71 (1.41%)	0/70 (0.00%)
Loss of consciousness † 1	1/71 (1.41%)	0/70 (0.00%)
Movement disorder † 1	1/71 (1.41%)	0/70 (0.00%)
Paraesthesia † 1	1/71 (1.41%)	0/70 (0.00%)
Polyneuropathy † 1	1/71 (1.41%)	0/70 (0.00%)
Psychiatric disorders
Delirium † 1	1/71 (1.41%)	0/70 (0.00%)
Depression † 1	1/71 (1.41%)	0/70 (0.00%)
Renal and urinary disorders
Urinary retention † 1	1/71 (1.41%)	1/70 (1.43%)
Acute kidney injury † 1	1/71 (1.41%)	0/70 (0.00%)
Haematuria † 1	0/71 (0.00%)	1/70 (1.43%)
Renal failure † 1	0/71 (0.00%)	1/70 (1.43%)
Ureteric stenosis † 1	0/71 (0.00%)	1/70 (1.43%)
Urethral stenosis † 1	1/71 (1.41%)	0/70 (0.00%)
Urinary tract pain † 1	1/71 (1.41%)	0/70 (0.00%)
Reproductive system and breast disorders
Prostatic obstruction † 1	0/71 (0.00%)	1/70 (1.43%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion † 1	2/71 (2.82%)	0/70 (0.00%)
Interstitial lung disease † 1	1/71 (1.41%)	0/70 (0.00%)
Vascular disorders
Deep vein thrombosis † 1	1/71 (1.41%)	1/70 (1.43%)
Circulatory collapse † 1	1/71 (1.41%)	0/70 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 17.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Tasquinimod	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	69/71 (97.18%)	66/70 (94.29%)
Blood and lymphatic system disorders
Anaemia † 1	9/71 (12.68%)	2/70 (2.86%)
Gastrointestinal disorders
Nausea † 1	19/71 (26.76%)	15/70 (21.43%)
Constipation † 1	23/71 (32.39%)	8/70 (11.43%)
Vomiting † 1	9/71 (12.68%)	9/70 (12.86%)
Diarrhoea † 1	9/71 (12.68%)	6/70 (8.57%)
Abdominal pain † 1	9/71 (12.68%)	4/70 (5.71%)
Flatulence † 1	4/71 (5.63%)	3/70 (4.29%)
Abdominal pain upper † 1	4/71 (5.63%)	1/70 (1.43%)
General disorders
Fatigue † 1	21/71 (29.58%)	15/70 (21.43%)
Asthenia † 1	17/71 (23.94%)	10/70 (14.29%)
Oedema peripheral † 1	13/71 (18.31%)	8/70 (11.43%)
Pain † 1	5/71 (7.04%)	4/70 (5.71%)
Pyrexia † 1	6/71 (8.45%)	3/70 (4.29%)
Influenza like illness † 1	5/71 (7.04%)	0/70 (0.00%)
Infections and infestations
Cystitis † 1	5/71 (7.04%)	2/70 (2.86%)
Injury, poisoning and procedural complications
Fall † 1	1/71 (1.41%)	5/70 (7.14%)
Investigations
Weight decreased † 1	6/71 (8.45%)	1/70 (1.43%)
Metabolism and nutrition disorders
Decreased appetite † 1	26/71 (36.62%)	8/70 (11.43%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	18/71 (25.35%)	15/70 (21.43%)
Back pain † 1	15/71 (21.13%)	14/70 (20.00%)
Pain in extremity † 1	11/71 (15.49%)	11/70 (15.71%)
Myalgia † 1	5/71 (7.04%)	10/70 (14.29%)
Bone pain † 1	6/71 (8.45%)	5/70 (7.14%)
Musculoskeletal chest pain † 1	6/71 (8.45%)	5/70 (7.14%)
Musculoskeletal pain † 1	7/71 (9.86%)	4/70 (5.71%)
Spinal pain † 1	4/71 (5.63%)	5/70 (7.14%)
Neck pain † 1	4/71 (5.63%)	2/70 (2.86%)
Nervous system disorders
Headache † 1	8/71 (11.27%)	7/70 (10.00%)
Paraesthesia † 1	6/71 (8.45%)	2/70 (2.86%)
Peripheral sensory neuropathy † 1	8/71 (11.27%)	0/70 (0.00%)
Dizziness † 1	4/71 (5.63%)	3/70 (4.29%)
Psychiatric disorders
Insomnia † 1	10/71 (14.08%)	6/70 (8.57%)
Depression † 1	4/71 (5.63%)	0/70 (0.00%)
Renal and urinary disorders
Urinary retention † 1	1/71 (1.41%)	5/70 (7.14%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	8/71 (11.27%)	3/70 (4.29%)
Pleural effusion † 1	4/71 (5.63%)	0/70 (0.00%)
Rhinorrhoea † 1	4/71 (5.63%)	0/70 (0.00%)
Skin and subcutaneous tissue disorders
Onycholysis † 1	4/71 (5.63%)	0/70 (0.00%)
Vascular disorders
Hypertension † 1	9/71 (12.68%)	6/70 (8.57%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 17.1

Limitations and Caveats

The study was terminated early due to the stop of the project as decided by sponsor. The trial included number of planned patients & number of events(PFS)were met to draw conclusions. Only follow-up of patients were discontinued earlier than planned.

More Information

Certain Agreements

Principal Investigators are NOT 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.

Results Point of Contact

• Name/Title: Medical Director, Oncology
• Organization: Ipsen
• Phone: clinical.trials@ipsen.com
• EMail: clinical.trials@ipsen.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Fizazi K, Ulys A, Sengelov L, Moe M, Ladoire S, Thiery-Vuillemin A, Flechon A, Guida A, Bellmunt J, Climent MA, Chowdhury S, Dumez H, Matouskova M, Penel N, Liutkauskiene S, Stachurski L, Sternberg CN, Baton F, Germann N, Daugaard G. A randomized, double-blind, placebo-controlled phase II study of maintenance therapy with tasquinimod in patients with metastatic castration-resistant prostate cancer responsive to or stabilized during first-line docetaxel chemotherapy. Ann Oncol. 2017 Nov 1;28(11):2741-2746. doi: 10.1093/annonc/mdx487.

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT01732549
• Other Study ID Numbers: 8-55-58102-002; 2012-001038-32 ( EudraCT Number )
• First Submitted: October 24, 2012
• First Posted: November 26, 2012
• Results First Submitted: April 29, 2016
• Results First Posted: October 3, 2016
• Last Update Posted: November 22, 2019