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

• Sponsor: Ipsen (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01732549
• Collaborator: (none)
• Enrollment: 144
• Locations: 58
• Arms: 2
• Duration (Months): 27.9
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to confirm that tasquinimod used as maintenance therapy is active and tolerable in patients with metastatic castrate-resistant prostate cancer not progressing after a first chemotherapy with docetaxel.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Castrate Resistant Prostate Cancer	Drug: Tasquinimod; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 144 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomised, Double-Blind, Placebo-Controlled 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
• Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tasquinimod 1 capsule daily, taken orally with water and food (0.25 mg initially then dose escalated to 0.5 mg or 1 mg per day) until disease progression or toxicity or patient's willingness to stop.	Drug: Tasquinimod; A patient's dose will escalate from one level to the next, once tolerability of the current dose is established. If tolerability issues arise at 0.5 or 1 mg/day, patients will have their dose reduced to 0.25 or 0.5 mg/day, respectively.
Placebo Comparator: Placebo 1 capsule daily, taken orally with water and food until disease progression or toxicity or patient's willingness to stop.	Drug: Placebo; Placebo capsules are identical to tasquinimod capsules in appearance and excipients but exclude the active compound (tasquinimod), to be taken orally once a day with water and food

Outcome Measures

Primary Outcome Measures

1. Time to Radiological Progression Free Survival [PFS] [Every 8 weeks until disease progression documentation (approximately up to 2.5 years)]

   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.

Secondary Outcome Measures

1. Overall Survival Based on Number of Subjects Who Died [Every 3 months after study treatment stop until death (approximately up to 2.5 years)]

   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

2. Time to Progression Free Survival [PFS] on Next-line Therapy (PFS 2) [Every 3 months after study treatment stop (follow-up) until progression under the next line therapy (approximately up to 2.5 years)]

   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.

3. Symptomatic PFS Based on Number of Subjects Who Had Symptomatic Progression or Death [Every 8 weeks until symptomatic or radiological progression documentation (approximately up to 2.5 years)]

   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

4. Time to Further Anticancer Treatment for Prostate Cancer [Every 3 months after study treatment stop until further anticancer therapy for prostate cancer (approximately up to 2.5 years)]

   Time from randomisation to further treatment for prostate cancer

5. Time to Deterioration in Functional Assessment of Cancer Therapy - Prostate (FACT-P) [Up to End of Study visit (approximately up to 2.5 years)]

   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)

6. Change From Baseline of EuroQol-5 Dimension QoL Instrument (EQ-5D) VAS Score [Baseline and End-of-study Visit (approximately up to 2.5 years)]

   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"

7. Safety Profile of Tasquinimod [At regular intervals during the study treatment period and every 3 months during the follow-up until death (approximately up to 2.5 years)]

   Number of subjects reporting adverse events

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically documented prostate cancer with evidence of metastatic disease on radiological evaluation, with or without symptoms (defined according to the BPI scale, with use of analgesics or narcotics)

• Has received a first line docetaxel based chemotherapy (as a monotherapy) every 3 weeks schedule of administration with corticosteroids for a minimum of 6 cycles with a cumulative dose ≥360 mg/m2. Any combination with investigational or non investigational agent is prohibited

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Docetaxel-related adverse effects must have been resolved to NCI-CTCAE v4.03 (Common Toxicity Criteria for Adverse Effects) Grade ≤1. Chemotherapy-induced alopecia and Grade 2 peripheral neuropathy are allowed

• No progressive disease at the end of docetaxel treatment defined according to RECIST criteria, no new lesion(s) assessed by bone scan and no elevated prostate specific antigen (PSA) for the three last tests with PSA3≤PSA2≤PSA1. The time between each PSA test should be preferably at least 14 days, however, a minimum of 7 days is acceptable.

Note: PSA value can be rounded to the nearest whole number if PSA>10 ng/mL. If the PSA3 value is above the PSA2, a fourth PSA test will be performed. The PSA4 value should be below or equal to PSA2

• Last dose of docetaxel administered between 21 and 42 days before randomisation

• Chemical or surgical castration verified by levels of serum testosterone ≤50 ng/dL (1.75 nmol/L)

Exclusion Criteria:

• Has concurrent use of other anticancer agents or treatments, with the following exceptions: ongoing treatment with luteinising hormone-releasing hormone agonists or antagonists, denosumab or bisphosphonate (e.g., zoledronic acid) is permitted if started ≥4 weeks prior to Screening. Ongoing treatment should be kept at a stable dose regimen

• Has ongoing treatment with warfarin

• Had prior radiation therapy since starting docetaxel. Exceptions may be made for palliative non-myelosuppressive radiation therapy administered more than 2 weeks prior to randomisation

• Had prior strontium, samarium or radium therapy or prior treatment with tasquinimod, or any agents with antiangiogenic properties

• Has ongoing treatment with corticosteroids at >10 mg/day prednisolone equivalent

• Has prostate cancer pain that warrants the initiation of radiotherapy or chemotherapy

• Has known brain or epidural metastases. Patients with previous medullary cord compression without any neurological deficit could be included

• Has a history of other malignancies, except adequately treated non-melanoma skin cancer or other solid tumours curatively treated, without evidence of disease for >5 years

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	AZ Maria Middelares	Gent		Belgium
2	UZ Gent	Gent		Belgium
3		Leuven		Belgium
4		Roeselare		Belgium
5		Praha	Hradčany	Czechia
6		Praha	Libeň	Czechia
7		Brno		Czechia
8		Olomouc		Czechia
9		Prague 2		Czechia
10		Aalborg		Denmark
11		Aarhus		Denmark
12		Herlev		Denmark
13		København		Denmark
14		Angers		France
15		Bordeaux		France
16		Clermont Ferrand		France
17		Dijon		France
18		Lille		France
19	Besancon	Lyon		France
20	Centre Leon Berard	Lyon		France
21	Hopital Edouard Herriot	Lyon		France
22		Paris		France
23		St Herblain		France
24		Toulouse		France
25		Villejuif		France
26		Aachen		Germany
27		Essen		Germany
28		München		Germany
29		Nürtingen		Germany
30		Tübingen		Germany
31	Bajcsy-Zsilinszky Kórház	Budapest		Hungary
32	Országos Onkológia Intézet	Budapest		Hungary
33	Uzsoki utcai Kórház	Budapest		Hungary
34		Genova		Italy
35		Milano		Italy
36		Modena		Italy
37		Pavia		Italy
38		Roma		Italy
39		Rozzano		Italy
40		Torino		Italy
41		Kaunas		Lithuania
42		Vilnius		Lithuania
43		Gdansk		Poland
44		Gdynia		Poland
45		Olsztyn		Poland
46	Urology and Urological Oncology Department and Clinic	Wroclaw		Poland
47	Wojewódzki Szpital Specjalistyczny we Wrocławiu	Wroclaw		Poland
48	Hospital Clinic Vllarroel	Barcelona		Spain
49	Hospital del Mar	Barcelona		Spain
50	Hospital Valle de Hebrón	Barcelona		Spain
51		Elche		Spain
52		Sabadell		Spain
53		Valencia		Spain
54		Leeds		United Kingdom
55	Guy's & St Thomas NHS Foundation	London		United Kingdom
56	The Royal Marsden NHS Trust	London		United Kingdom
57	University College Hospitals London	London		United Kingdom
58		Sutton		United Kingdom

Sponsors and Collaborators

• Ipsen

Investigators

• Study Director: Ipsen Medical Director, Ipsen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT01732549
• Other Study ID Numbers: 8-55-58102-002; 2012-001038-32
• First Posted: Nov 26, 2012
• Last Update Posted: Nov 22, 2019
• Last Verified: Nov 1, 2019

• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

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 Detail	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	61
Ongoing Treatment Period:Final Analysis	0	0
Withdrawn During Treatment:Final Analysi	71	73
COMPLETED	0	0
NOT COMPLETED	71	73

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 Participants	71	73	144
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69.6 (7.18)	69.6 (5.57)	69.6 (6.39)
Age, Customized (participants) [Number]
18 to ≤ 65 years	18 25.4%	17 23.3%	35 24.3%
66 to ≤ 75 years	40 56.3%	45 61.6%	85 59%
> 75 years	13 18.3%	11 15.1%	24 16.7%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	71 100%	73 100%	144 100%
Race/Ethnicity, Customized (participants) [Number]
Black/African American	0 0%	1 1.4%	1 0.7%
Caucasian/White	52 73.2%	58 79.5%	110 76.4%
Multiple Race	1 1.4%	0 0%	1 0.7%
Missing	18 25.4%	14 19.2%	32 22.2%
Region of Enrollment (participants) [Number]
Czech Republic	5 7%	1 1.4%	6 4.2%
Belgium	5 7%	6 8.2%	11 7.6%
Hungary	2 2.8%	2 2.7%	4 2.8%
Denmark	6 8.5%	13 17.8%	19 13.2%
Poland	4 5.6%	3 4.1%	7 4.9%
Italy	9 12.7%	5 6.8%	14 9.7%
United Kingdom	8 11.3%	6 8.2%	14 9.7%
France	17 23.9%	14 19.2%	31 21.5%
Lithuania	7 9.9%	10 13.7%	17 11.8%
Germany	3 4.2%	3 4.1%	6 4.2%
Spain	5 7%	10 13.7%	15 10.4%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	83.7 (12.57)	83.4 (15.09)	83.6 (13.86)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	27.67 (3.543)	28.01 (4.399)	27.84 (3.987)
Ethnicity (participants) [Number]
Hispanic or Latino	2 2.8%	4 5.5%	6 4.2%
Not Hispanic or Latino	52 73.2%	55 75.3%	107 74.3%
Missing	17 23.9%	14 19.2%	31 21.5%
ECOG Performance Status Score (participants) [Number]
0 (Normal Activity)	39 54.9%	31 42.5%	70 48.6%
1 (Restricted Activity)	32 45.1%	38 52.1%	70 48.6%
Missing	0 0%	4 5.5%	4 2.8%
Region (participants) [Number]
Eastern Europe	18 25.4%	16 21.9%	34 23.6%
Western Europe	53 74.6%	57 78.1%	110 76.4%

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
Measure Participants	71	73
Median (90% Confidence Interval) [weeks]	31.7	22.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasquinimod, Placebo
	Comments	Stratified[a]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
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

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tasquinimod, Placebo
	Comments	Unstratified[b]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	=0.0344
	Comments
	Method	Log Rank
	Comments

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
Measure Participants	71	73
Number [participants]	8 11.3%	6 8.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasquinimod, Placebo
	Comments	Stratified[a]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	=0.4430
	Comments
	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
Measure Participants	71	73
Median (90% Confidence Interval) [weeks]	19.3	24.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasquinimod, Placebo
	Comments	Stratified[a]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.5219
	Comments
	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
Measure Participants	71	73
Number [participants]	23 32.4%	19 26%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasquinimod, Placebo
	Comments	Stratified[a]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	=0.5442
	Comments
	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
Measure Participants	71	73
Median (90% Confidence Interval) [weeks]	42.3	29.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasquinimod, Placebo
	Comments	Stratified[a]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	=0.1120
	Comments
	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
Measure Participants	71	73
Median (90% Confidence Interval) [weeks]	8.1	15.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasquinimod, Placebo
	Comments	Stratified[a]
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	=0.2491
	Comments
	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
Measure Participants	39	50
Median (Inter-Quartile Range) [Score on scale]	-9.0	-3.5

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
Measure Participants	71	70
Any Treatment Emergent Adverse Event (TEAEs)	69 97.2%	66 90.4%
Intensity of TEAEs [Grade 3-5 (severe)]	36 50.7%	19 26%
Intensity of TEAEs [Grade 5]	1 1.4%	3 4.1%
Intensity of TEAEs [Grade 4]	3 4.2%	2 2.7%
Intensity of TEAEs [Grade 3]	32 45.1%	14 19.2%
Intensity of TEAEs [Grade 2 (moderate)]	28 39.4%	28 38.4%
Intensity of TEAEs [Grade 1 (mild)]	5 7%	19 26%
Causality of TEAEs [Drug Related]	54 76.1%	38 52.1%
Causality of TEAEs [Not Drug Related]	15 21.1%	28 38.4%
TEAEs Leading to Drug Withdrawal	12 16.9%	3 4.1%
TEAEs leading to Dose Reduction	16 22.5%	2 2.7%
TEAEs leading to Drug Interruption	33 46.5%	12 16.4%
TEAEs Leading to Death	1 1.4%	0 0%
Serious Adverse Event (SAEs)	24 33.8%	16 21.9%
Drug Related SAEs	6 8.5%	2 2.7%

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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Tasquinimod		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/71 (33.8%)		16/70 (22.9%)
Blood and lymphatic system disorders
Anaemia	1/71 (1.4%)		0/70 (0%)
Cardiac disorders
Myocardial ischaemia	1/71 (1.4%)		1/70 (1.4%)
Arteriosclerosis coronary artery	1/71 (1.4%)		0/70 (0%)
Cardiac failure	1/71 (1.4%)		0/70 (0%)
Myocardial infarction	1/71 (1.4%)		0/70 (0%)
Pericarditis	0/71 (0%)		1/70 (1.4%)
Eye disorders
Dacryostenosis acquired	0/71 (0%)		1/70 (1.4%)
Gastrointestinal disorders
Vomiting	2/71 (2.8%)		1/70 (1.4%)
Ileus	1/71 (1.4%)		1/70 (1.4%)
Nausea	1/71 (1.4%)		1/70 (1.4%)
Abdominal pain	0/71 (0%)		1/70 (1.4%)
Colitis	1/71 (1.4%)		0/70 (0%)
Constipation	0/71 (0%)		1/70 (1.4%)
Large intestine perforation	1/71 (1.4%)		0/70 (0%)
Proctitis	1/71 (1.4%)		0/70 (0%)
General disorders
Fatigue	1/71 (1.4%)		1/70 (1.4%)
Disease progression	1/71 (1.4%)		0/70 (0%)
General physical health deterioration	0/71 (0%)		1/70 (1.4%)
Pyrexia	1/71 (1.4%)		0/70 (0%)
Hepatobiliary disorders
Biliary cyst	1/71 (1.4%)		0/70 (0%)
Infections and infestations
Urinary tract infection	1/71 (1.4%)		1/70 (1.4%)
Appendicitis perforated	0/71 (0%)		1/70 (1.4%)
Bronchitis	0/71 (0%)		1/70 (1.4%)
Erysipelas	0/71 (0%)		1/70 (1.4%)
Pyelonephritis acute	1/71 (1.4%)		0/70 (0%)
Injury, poisoning and procedural complications
Facial bones fracture	0/71 (0%)		1/70 (1.4%)
Fall	0/71 (0%)		1/70 (1.4%)
Laceration	0/71 (0%)		1/70 (1.4%)
Spinal fracture	1/71 (1.4%)		0/70 (0%)
Investigations
Blood creatinine increased	1/71 (1.4%)		0/70 (0%)
Metabolism and nutrition disorders
Decreased appetite	2/71 (2.8%)		0/70 (0%)
Fluid retention	1/71 (1.4%)		0/70 (0%)
Musculoskeletal and connective tissue disorders
Chondrocalcinosis	1/71 (1.4%)		0/70 (0%)
Lumbar spinal stenosis	1/71 (1.4%)		0/70 (0%)
Muscular weakness	1/71 (1.4%)		0/70 (0%)
Pain in extremity	1/71 (1.4%)		0/70 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/71 (0%)		1/70 (1.4%)
Metastases to central nervous system	0/71 (0%)		1/70 (1.4%)
Nervous system disorders
Headache	1/71 (1.4%)		0/70 (0%)
Loss of consciousness	1/71 (1.4%)		0/70 (0%)
Movement disorder	1/71 (1.4%)		0/70 (0%)
Paraesthesia	1/71 (1.4%)		0/70 (0%)
Polyneuropathy	1/71 (1.4%)		0/70 (0%)
Psychiatric disorders
Delirium	1/71 (1.4%)		0/70 (0%)
Depression	1/71 (1.4%)		0/70 (0%)
Renal and urinary disorders
Urinary retention	1/71 (1.4%)		1/70 (1.4%)
Acute kidney injury	1/71 (1.4%)		0/70 (0%)
Haematuria	0/71 (0%)		1/70 (1.4%)
Renal failure	0/71 (0%)		1/70 (1.4%)
Ureteric stenosis	0/71 (0%)		1/70 (1.4%)
Urethral stenosis	1/71 (1.4%)		0/70 (0%)
Urinary tract pain	1/71 (1.4%)		0/70 (0%)
Reproductive system and breast disorders
Prostatic obstruction	0/71 (0%)		1/70 (1.4%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	2/71 (2.8%)		0/70 (0%)
Interstitial lung disease	1/71 (1.4%)		0/70 (0%)
Vascular disorders
Deep vein thrombosis	1/71 (1.4%)		1/70 (1.4%)
Circulatory collapse	1/71 (1.4%)		0/70 (0%)
Other (Not Including Serious) Adverse Events
	Tasquinimod		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	69/71 (97.2%)		66/70 (94.3%)
Blood and lymphatic system disorders
Anaemia	9/71 (12.7%)		2/70 (2.9%)
Gastrointestinal disorders
Nausea	19/71 (26.8%)		15/70 (21.4%)
Constipation	23/71 (32.4%)		8/70 (11.4%)
Vomiting	9/71 (12.7%)		9/70 (12.9%)
Diarrhoea	9/71 (12.7%)		6/70 (8.6%)
Abdominal pain	9/71 (12.7%)		4/70 (5.7%)
Flatulence	4/71 (5.6%)		3/70 (4.3%)
Abdominal pain upper	4/71 (5.6%)		1/70 (1.4%)
General disorders
Fatigue	21/71 (29.6%)		15/70 (21.4%)
Asthenia	17/71 (23.9%)		10/70 (14.3%)
Oedema peripheral	13/71 (18.3%)		8/70 (11.4%)
Pain	5/71 (7%)		4/70 (5.7%)
Pyrexia	6/71 (8.5%)		3/70 (4.3%)
Influenza like illness	5/71 (7%)		0/70 (0%)
Infections and infestations
Cystitis	5/71 (7%)		2/70 (2.9%)
Injury, poisoning and procedural complications
Fall	1/71 (1.4%)		5/70 (7.1%)
Investigations
Weight decreased	6/71 (8.5%)		1/70 (1.4%)
Metabolism and nutrition disorders
Decreased appetite	26/71 (36.6%)		8/70 (11.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	18/71 (25.4%)		15/70 (21.4%)
Back pain	15/71 (21.1%)		14/70 (20%)
Pain in extremity	11/71 (15.5%)		11/70 (15.7%)
Myalgia	5/71 (7%)		10/70 (14.3%)
Bone pain	6/71 (8.5%)		5/70 (7.1%)
Musculoskeletal chest pain	6/71 (8.5%)		5/70 (7.1%)
Musculoskeletal pain	7/71 (9.9%)		4/70 (5.7%)
Spinal pain	4/71 (5.6%)		5/70 (7.1%)
Neck pain	4/71 (5.6%)		2/70 (2.9%)
Nervous system disorders
Headache	8/71 (11.3%)		7/70 (10%)
Paraesthesia	6/71 (8.5%)		2/70 (2.9%)
Peripheral sensory neuropathy	8/71 (11.3%)		0/70 (0%)
Dizziness	4/71 (5.6%)		3/70 (4.3%)
Psychiatric disorders
Insomnia	10/71 (14.1%)		6/70 (8.6%)
Depression	4/71 (5.6%)		0/70 (0%)
Renal and urinary disorders
Urinary retention	1/71 (1.4%)		5/70 (7.1%)
Respiratory, thoracic and mediastinal disorders
Cough	8/71 (11.3%)		3/70 (4.3%)
Pleural effusion	4/71 (5.6%)		0/70 (0%)
Rhinorrhoea	4/71 (5.6%)		0/70 (0%)
Skin and subcutaneous tissue disorders
Onycholysis	4/71 (5.6%)		0/70 (0%)
Vascular disorders
Hypertension	9/71 (12.7%)		6/70 (8.6%)

Limitations/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.