TasQ003: Study Of Tasquinimod In Asian Chemo-Naïve Patients With Metastatic Castrate-Resistant Prostate Cancer

• Sponsor: Ipsen (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02057666
• Collaborator: (none)
• Enrollment: 146
• Locations: 36
• Arms: 2
• Duration (Months): 15.9
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The primary objective was to confirm the effect of tasquinimod in delaying disease progression or death as compared with placebo in chemo-naïve patients with metastatic castrate-resistant prostate cancer (mCRPC).

Secondary objectives included further evaluation of the safety profile of tasquinimod, comparison of clinical benefits (such as overall survival and symptoms) of tasquinimod with placebo, to evaluate the quality of life impact and to determine the pharmacokinetics of tasquinimod.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms, Castration-Resistant	Drug: Tasquinimod; Drug: Placebo	Phase 3

Detailed Description

The study involved a 4-week Screening Period, Baseline Visit (Day 1) where the patient was randomised, followed by a Double Blind Treatment Period. Patients initially received tasquinimod (or corresponding placebo) at a 0.25 mg/day dose which was then titrated through 0.5 mg/day (from Day 15) to a maximum of 1 mg/day (from Day 29). If tolerability issues arose at 0.5 or 1 mg/day, patients had their dose reduced to 0.25 or 0.5 mg/day, respectively. The Double Blind Treatment Period continued until the death of the patient or any criterion for withdrawal from study treatment was reached. Any placebo treated patients with radiological disease progression confirmed by the central imaging assessment, who remained asymptomatic or mildly symptomatic were, at the Investigator's discretion, given the option to continue on active treatment (tasquinimod) during an Open-Label Treatment Period, following the same titration rule described above until progression under active treatment. All other patients stopped study treatment.

An End-of-Study Treatment/Withdrawal Visit was to be performed within 14 days after the last dose of study treatment and patients were then to be followed up every 6 months until 80% of the patients had died or 2 years after the last patient was randomised, whichever occurred last.

A PK ancillary study was to be performed in a subgroup of 12 Asian-Chinese patients before randomisation; however, due to the early termination of this study, only some samples were analysed and no PK analyses were performed.

Study Design

• Study Type: Interventional
• Actual Enrollment: 146 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III, Randomised, Double-Blind, Placebo-Controlled Study Of Tasquinimod In Asian Chemo-Naïve Patients With Metastatic Castrate-Resistant Prostate Cancer
• Study Start Date: Jan 1, 2014
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tasquinimod One capsule (0.25, 0.50 or 1 mg), taken orally once a day with water and food (preferably the main evening meal).	Drug: Tasquinimod; A patient initially received a 0.25 mg/day dose which was then titrated through 0.5 mg/day (from Day 15) to a maximum of 1 mg/day (from Day 29). If tolerability issues arose at 0.5 or 1 mg/day, patients had their dose reduced to 0.25 or 0.5 mg/day, respectively.; Other Names: ABR-215050
Placebo Comparator: Placebo One capsule, taken orally once a day with water and food (preferably the main evening meal).	Drug: Placebo; Placebo capsules were identical to tasquinimod capsules in appearance and excipients but excluded the active compound (tasquinimod).

Outcome Measures

Primary Outcome Measures

1. Time to Radiological Progression-Free Survival (PFS) [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years]

   PFS was defined as the time from the date of randomisation to the date of radiological progression (confirmed by the central imaging assessment) or death due to any cause. Radiological progression was defined by any of the following criteria: progression of soft tissue lesions evaluated by computed tomography (CT) or magnetic resonance imaging (MRI) scan according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 criteria; progression of bone lesions detected with bone scan according to Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria; or radiologically confirmed spinal cord compression or pathological fracture due to malignant progression. The primary endpoint was centrally and independently evaluated.

Secondary Outcome Measures

1. Overall Survival [From randomisation up to 3 years]

   An overall survival event was defined as death due to any cause. The number of participants with overall survival events is reported.

2. Local Assessment of Radiological PFS [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years]

   The Investigator was to evaluate radiological disease progression in accordance with the criteria defined for the primary endpoint.

3. Time to Symptomatic PFS Based on Local Assessment [Every 3 months]

   Symptomatic PFS, defined as the time from the date of randomisation to the date of appearance of pain (using pain visual analogue scale (VAS)) at a site with documented disease and analgesic use, or skeletal-related events, or death due to prostate cancer, whichever occurred first.

4. Time From Randomisation to Further Treatment for Prostate Cancer [Every 6 months during the follow-up period]

   The need for any anti-tumour prostate cancer treatments was to be recorded during the Follow-up Period, with the time to further treatment to subsequently be derived.

5. Quality of Life (QoL) [Every 3 months]

   QoL measured by the Functional Assessment of Cancer Therapy Prostate Module (FACT-P) questionnaire and by the EuroQol 5-Dimension QoL Instrument (EQ-5D). Due to the early termination of the study, a simplified data analysis (primary endpoint and overall survival) was performed to fulfil the requirement from regulatory authorities for early termination studies. Therefore, no analyses were performed on this secondary efficacy endpoint.

6. Tasquinimod Pharmacokinetic (PK) Profile [Up to 216 hours after a single dose and during the double blind treatment period (Day 15, 29, 57 and 127)]

   Tasquinimod PK profile: Following a single 1 mg dose of tasquinimod given to a subgroup of 12 Asian-Chinese patients (ancillary study). At steady state conditions based on limited sampling strategy. Following termination of the study the PK analyses were not performed.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Asian male aged at least 20 years at the time of signing the informed consent form.

2. Histologically confirmed diagnosis of adenocarcinoma of the prostate.

3. Evidence of metastatic disease (bone and/or visceral), excluding node lesion only, on radiographic examination, whether from bone scan (bone lesions) or other imaging modality (CT scan/MRI).

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

5. Evidence of progressive disease after castration levels of testosterone had been achieved, defined by any of the following criteria:

• Increasing serum Prostate Specific Antigen (PSA) levels, with the most recent value ≥2 ng/mL (increasing levels must have been confirmed by three consecutive PSA measurements, within 15 months prior to the start of study treatment. The time between each PSA test should have been preferably at least 14 days, however a minimum of 7 days was acceptable. The third value was used for study selection).

• Progression of soft tissue metastasis documented within 6 weeks prior to randomisation (CT scan or MRI).

• Progression of bone disease (at least one new bone lesion as measured by bone scan within the 12 weeks prior to the start of study treatment).

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

2. Laboratory values as follows:

• Haemoglobin ≥90 g/L (≥9 g/dL).

• Absolute neutrophil count ≥1500/μL.

• Platelets ≥100,000/μL.

• Serum creatinine ≤1.5 times the upper limit of normal (ULN).

• Total bilirubin ≤1.5 times ULN.

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 times ULN (≤5 times ULN if liver metastases were present).

• Serum amylase ≤ULN (if serum amylase >ULN, pancreatic amylase and serum lipase should have been analysed. If both pancreatic amylase and serum lipase were >ULN, patient excluded).

1. If sexually active with partner of childbearing potential, patient agreed to use adequate contraceptive method (barrier contraceptive with spermicide) while receiving study treatment and until 14 days after the stop of study treatment or had been previously vasectomised.

2. No evidence (within last 5 years) of prior malignancies (except successfully treated basal cell or squamous cell carcinoma of the skin).

3. Able to swallow and retain oral medication.

4. Able to adhere to the study visit schedule and other protocol requirements.

5. Ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to cooperate with the Investigator and to comply with the requirements of the entire study.

6. Able to sign and date the written informed consent after being informed of the full nature and purpose of the study, including possible risks and side effects, and given ample time and opportunity to read and understand this information.

Exclusion Criteria:

1. Cytotoxic chemotherapy for the treatment of prostate cancer within 2 years prior to the start of study treatment.

2. Previous anticancer therapy using radiation, biologics or vaccines and including sipuleucel-T (Provenge®) within 4 weeks prior to the start of study treatment and abiraterone, TAK700 or MDV3100 within 2 weeks prior to the start of study treatment. Before inclusion, abiraterone, TAK700 or MDV3100 related adverse effect must have been resolved to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 Grade ≤1. If radiation therapy was applied after Baseline scan, a new Baseline scan needed to be done at least 4 weeks after the radiation therapy.

3. Therapy with antiandrogens within 4 weeks (within 6 weeks for bicalutamide e.g. Casodex®) prior to the start of study treatment.

4. Concurrent use of other anticancer agents or treatments, with the exception of ongoing treatment with luteinising hormone-releasing hormone (LHRH) agonists or antagonists, denosumab (Prolia®) or bisphosphonate (e.g. zoledronic acid), which were allowed. Ongoing treatment was to be kept at a stable schedule; however, if medically required, a change of dose, compound, or both was allowed.

5. Any treatment modalities involving major surgery within 4 weeks prior to the start of study treatment.

6. Prostate cancer pain that required ongoing treatment with narcotic analgesics or warranted the initiation of radio- or chemotherapy.

7. Both of the following criteria:

• Visceral metastasis.

• Bone lesions both on and outside of the spinal axis.

1. PSA >100 ng/mL.

2. Ongoing treatment with warfarin.

3. Maintenance treatment with corticosteroids corresponding to a prednisolone or prednisone dose above 10 mg/day. The dose must have been stable for at least 5 days.

4. Systemic exposure to ketoconazole or other strong cytochrome P450 (CYP) 3A4 isozyme inhibitors or inducers within 14 days prior to the start of study treatment. Systemic exposure to amiodarone was not allowed within 1 year prior to the start of study treatment.

5. Ongoing treatment with sensitive CYP1A2 substrate or CYP1A2 substrate with narrow therapeutic range at the start of study treatment.

6. Ongoing treatment with CYP3A4 substrate with narrow therapeutic range at the start of study treatment.

7. Simultaneous participation in any other study involving treatment with investigational drugs or having received treatment with investigational drugs less than 4 weeks prior to the start of study treatment.

8. Myocardial infarction, percutaneous coronary intervention, acute coronary syndrome, coronary artery bypass graft, New York Heart Association (NYHA) class III/IV congestive heart failure, cerebrovascular accident, transient ischaemic attack, or limb claudication at rest, within 6 months prior to start of study treatment, history of venous thrombo-embolic disease within 3 months prior to randomisation and ongoing symptomatic dysrhythmias, unstable angina, uncontrolled hypertension, and uncontrolled atrial or ventricular arrhythmias.

9. History of pancreatitis.

10. Known brain or epidural metastases.

11. Known positive serology for human immunodeficiency virus (HIV) (patients with known history of HIV were excluded because of potential for unforeseen toxicity and morbidity in an immunocompromised host).

12. Chronic hepatitis with advanced, decompensated hepatic disease or cirrhosis of the liver or history of a chronic viral hepatitis or known viral hepatitis carrier (patients who had recovered from hepatitis were allowed to enter the study) with abnormal liver function.

13. Patients with active tuberculosis (TB), or with known, untreated latent TB (country-specific TB therapy should have been given for at least 30 days prior to the start of study treatment and the patient should have intended to complete the entire course of that therapy).

14. Any condition, including other active or latent infections, medical or psychiatric conditions, or the presence of laboratory abnormalities, which could have confounded the ability to interpret data from the study or placed the patient at unacceptable risk if he participated in the study.

15. Any patient who in the opinion of the Investigator should not have participated in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beijing Chao-Yang Hospital Capital Medical University	Beijing	Beijing	China	100020
2	Peking University First Hospital	Beijing	Beijing	China	100034
3	Peking University People's Hospital	Beijing	Beijing	China	100044
4	Beijing Friendship Hospital Capital Medical University	Beijing	Beijing	China	100050
5	Peking University Third Hospital	Beijing	Beijing	China	100191
6	Peking Union Medical College Hospital	Beijing	Beijing	China	100370
7	Beijing Hospital of Ministry of Health	Beijing	Beijing	China	100730
8	Southwest Hospital (the First Affiliated Hospital of Third Military Medical University PLA)	Chongqing	Chongqing	China	400038
9	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong	China	510000
10	Guangshou First People's Hospital	Guangzhou	Guangdong	China	510180
11	Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology	Wuhan	Hubei	China	430030
12	Jiangsu Cancer Hospital	Nanjing	Jiangsu	China	210009
13	The Second Affiliated Hospital of Soochow University	Suzhou	Jiangsu	China	215004
14	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi	China	330006
15	Ruijin Hospital Shanghai Jiaotong University of Medicine	Shanghai	Shanghai	China	200025
16	Fudan University Shanghai Cancer Center	Shanghai	Shanghai	China	200032
17	Zhongshan Hospital Fudan University	Shanghai	Shanghai	China	200032
18	Huadong Hospital Fudan University	Shanghai	Shanghai	China	200040
19	Huashan Hospital Fudan University	Shanghai	Shanghai	China	200040
20	Shanghai Tenth People's Hospital	Shanghai	Shanghai	China	200072
21	Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai	China	200092
22	West China Hospital Sichuan University	Chengdu	Sichuan	China	61004
23	Sichuan Academy of Sichuan Medical Sciences & Sichuan Provincial People's Hospital	Chengdu	Sichuan	China	610072
24	General Hospital Chengdu Military Region of PLA	Chengdu	Sichuan	China	610083
25	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin	China	300060
26	The First Affiliated Hospital College of Medicine Zhujiang University	Hangzhou	Zhejiang	China	310003
27	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang	China	325000
28	Chungbuk National University Hospital	Cheongju	Chungcheong Province	Korea, Republic of	361-711
29	Chonnam National University Hospital	Gwangju		Korea, Republic of	501-757
30	Gangnam Severance Hospital	Seoul		Korea, Republic of	135-720
31	The Catholic University of Korea Seoul St. Mary's Hospital	Seoul		Korea, Republic of	137-701
32	Asan Medical Center	Seoul		Korea, Republic of	138-736
33	China Medical University Hospital	Taichung		Taiwan	40447
34	Taichung Veterans General Hospital	Taichung		Taiwan	40705
35	National Taiwan University Hospital	Taipei		Taiwan	10002
36	Taipei Veterans General Hospital	Taipei		Taiwan	11217

Sponsors and Collaborators

• Ipsen

Investigators

• Study Director: Medical Director Uro-Oncology, Ipsen

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ipsen
• ClinicalTrials.gov Identifier: NCT02057666
• Other Study ID Numbers: 8-55-58102-003
• First Posted: Feb 7, 2014
• Last Update Posted: Apr 23, 2021
• Last Verified: Mar 1, 2021

• Keywords provided by Ipsen: CRPC; Metastatic; Chemotherapy naïve; Chemo-naïve; Prostate cancer; mCRPC; Chemotherapy-naïve; Chemo naïve
• Additional relevant MeSH terms: Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant

Study Results

Participant Flow

Recruitment Details	Patients were recruited across 36 centres. The first patient first visit was on 24 January 2014. The last patient was randomised into the study on 16 April 2015; however, early termination of the study was announced on the same day. Due to a necessary visit for 1 patient, the last patient last visit of the study was on 26 May 2015.
Pre-assignment Detail	229 patients were screened, of whom 146 were randomised (96 tasquinimod, 50 placebo).

Arm/Group Title	Tasquinimod	Placebo
Arm/Group Description	One capsule (0.25, 0.50 or 1 mg), taken orally once a day with water and food (preferably the main evening meal). A patient initially received 0.25 mg/day dose which was then titrated through 0.5 mg/day (from Day 15) to a maximum of 1 mg/day (from Day 29). If tolerability issues arose at 0.5 or 1 mg/day, patients had their dose reduced to 0.25 or 0.5 mg/day, respectively.	One capsule, taken orally once a day with water and food (preferably the main evening meal). Placebo capsules were identical to tasquinimod capsules in appearance and excipients but excluded the active compound (tasquinimod).
Period Title: Double Blind Treatment Period
STARTED	96	50
COMPLETED	0	6
NOT COMPLETED	96	44
Period Title: Double Blind Treatment Period
STARTED	0	6
COMPLETED	0	0
NOT COMPLETED	0	6

Baseline Characteristics

Arm/Group Title	Tasquinimod	Placebo	Total
Arm/Group Description	One capsule (0.25, 0.50 or 1 mg), taken orally once a day with water and food (preferably the main evening meal). A patient initially received a 0.25 mg/day dose which was then titrated through 0.5 mg/day (from Day 15) to a maximum of 1 mg/day (from Day 29). If tolerability issues arose at 0.5 or 1 mg/day, patients had their dose reduced to 0.25 or 0.5 mg/day, respectively.	One capsule, taken orally once a day with water and food (preferably the main evening meal). Placebo capsules were identical to tasquinimod capsules in appearance and excipients but excluded the active compound (tasquinimod).	Total of all reporting groups
Overall Participants	96	50	146
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	16 16.7%	9 18%	25 17.1%
>=65 years	80 83.3%	41 82%	121 82.9%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	96 100%	50 100%	146 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	96 100%	50 100%	146 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
China	69 71.9%	34 68%	103 70.5%
Taiwan	5 5.2%	5 10%	10 6.8%
Korea, Republic of	22 22.9%	11 22%	33 22.6%
Status of Visceral Metastases (Count of Participants)
Presence	4 4.2%	2 4%	6 4.1%
Absence	92 95.8%	48 96%	140 95.9%

Outcome Measures

1. Primary Outcome

Title	Time to Radiological Progression-Free Survival (PFS)
Description	PFS was defined as the time from the date of randomisation to the date of radiological progression (confirmed by the central imaging assessment) or death due to any cause. Radiological progression was defined by any of the following criteria: progression of soft tissue lesions evaluated by computed tomography (CT) or magnetic resonance imaging (MRI) scan according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 criteria; progression of bone lesions detected with bone scan according to Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria; or radiologically confirmed spinal cord compression or pathological fracture due to malignant progression. The primary endpoint was centrally and independently evaluated.
Time Frame	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years

Outcome Measure Data

Analysis Population Description

ITT population: All randomised patients. Patients were allocated to the treatment they were randomised to. This population consisted of all randomised patients regardless of whether or not the patient received any dose of the study treatment.

Arm/Group Title	Tasquinimod	Placebo
Arm/Group Description	One capsule (0.25, 0.50 or 1 mg), taken orally once a day with water and food (preferably the main evening meal). A patient initially received a 0.25 mg/day dose which was then titrated through 0.5 mg/day (from Day 15) to a maximum of 1 mg/day (from Day 29). If tolerability issues arose at 0.5 or 1 mg/day, patients had their dose reduced to 0.25 or 0.5 mg/day, respectively.	One capsule, taken orally once a day with water and food (preferably the main evening meal). Placebo capsules were identical to tasquinimod capsules in appearance and excipients but excluded the active compound (tasquinimod).
Measure Participants	96	50
Median (95% Confidence Interval) [months]	11.00	7.53

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasquinimod, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.027
	Comments
	Method	Log Rank
	Comments	Stratified as per randomisation.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.406
	Confidence Interval	(2-Sided) 95%; 0.182 to 0.903
	Parameter Dispersion	Type: Value:
	Estimation Comments	Stratified as per randomisation.

2. Secondary Outcome

Title	Overall Survival
Description	An overall survival event was defined as death due to any cause. The number of participants with overall survival events is reported.
Time Frame	From randomisation up to 3 years

Outcome Measure Data

Analysis Population Description

ITT population: All randomised patients. Patients were allocated to the treatment they were randomised to. This population consisted of all randomised patients regardless of whether or not the patient received any dose of the study treatment.

Arm/Group Title	Tasquinimod	Placebo
Arm/Group Description	One capsule (0.25, 0.50 or 1 mg), taken orally once a day with water and food (preferably the main evening meal). A patient initially received a 0.25 mg/day dose which was then titrated through 0.5 mg/day (from Day 15) to a maximum of 1 mg/day (from Day 29). If tolerability issues arose at 0.5 or 1 mg/day, patients had their dose reduced to 0.25 or 0.5 mg/day, respectively.	One capsule, taken orally once a day with water and food (preferably the main evening meal). Placebo capsules were identical to tasquinimod capsules in appearance and excipients but excluded the active compound (tasquinimod).
Measure Participants	96	50
Number of deaths	2 2.1%	2 4%
Number of censored observations	94 97.9%	48 96%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tasquinimod, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.448
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.465
	Confidence Interval	(2-Sided) 95%; 0.065 to 3.355
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Local Assessment of Radiological PFS
Description	The Investigator was to evaluate radiological disease progression in accordance with the criteria defined for the primary endpoint.
Time Frame	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years

Outcome Measure Data

Analysis Population Description

No data collected due to the early termination of the study. Therefore, no analyses performed on this secondary efficacy endpoint.

Arm/Group Title	Tasquinimod	Placebo
Arm/Group Description	One capsule (0.25, 0.50 or 1 mg), taken orally once a day with water and food (preferably the main evening meal). A patient initially received a 0.25 mg/day dose which was then titrated through 0.5 mg/day (from Day 15) to a maximum of 1 mg/day (from Day 29). If tolerability issues arose at 0.5 or 1 mg/day, patients had their dose reduced to 0.25 or 0.5 mg/day, respectively.	One capsule, taken orally once a day with water and food (preferably the main evening meal). Placebo capsules were identical to tasquinimod capsules in appearance and excipients but excluded the active compound (tasquinimod).
Measure Participants	0	0

4. Secondary Outcome

Title	Time to Symptomatic PFS Based on Local Assessment
Description	Symptomatic PFS, defined as the time from the date of randomisation to the date of appearance of pain (using pain visual analogue scale (VAS)) at a site with documented disease and analgesic use, or skeletal-related events, or death due to prostate cancer, whichever occurred first.
Time Frame	Every 3 months

Outcome Measure Data

Analysis Population Description

No data collected due to the early termination of the study. Therefore, no analyses performed on this secondary efficacy endpoint.

Arm/Group Title	Tasquinimod	Placebo
Arm/Group Description	One capsule (0.25, 0.50 or 1 mg), taken orally once a day with water and food (preferably the main evening meal). A patient initially received a 0.25 mg/day dose which was then titrated through 0.5 mg/day (from Day 15) to a maximum of 1 mg/day (from Day 29). If tolerability issues arose at 0.5 or 1 mg/day, patients had their dose reduced to 0.25 or 0.5 mg/day, respectively.	One capsule, taken orally once a day with water and food (preferably the main evening meal). Placebo capsules were identical to tasquinimod capsules in appearance and excipients but excluded the active compound (tasquinimod).
Measure Participants	0	0

5. Secondary Outcome

Title	Time From Randomisation to Further Treatment for Prostate Cancer
Description	The need for any anti-tumour prostate cancer treatments was to be recorded during the Follow-up Period, with the time to further treatment to subsequently be derived.
Time Frame	Every 6 months during the follow-up period

Outcome Measure Data

Analysis Population Description

No data collected due to the early termination of the study. Therefore, no analyses performed on this secondary efficacy endpoint.

Arm/Group Title	Tasquinimod	Placebo
Arm/Group Description	One capsule (0.25, 0.50 or 1 mg), taken orally once a day with water and food (preferably the main evening meal). A patient initially received a 0.25 mg/day dose which was then titrated through 0.5 mg/day (from Day 15) to a maximum of 1 mg/day (from Day 29). If tolerability issues arose at 0.5 or 1 mg/day, patients had their dose reduced to 0.25 or 0.5 mg/day, respectively.	One capsule, taken orally once a day with water and food (preferably the main evening meal). Placebo capsules were identical to tasquinimod capsules in appearance and excipients but excluded the active compound (tasquinimod).
Measure Participants	0	0

6. Secondary Outcome

Title	Quality of Life (QoL)
Description	QoL measured by the Functional Assessment of Cancer Therapy Prostate Module (FACT-P) questionnaire and by the EuroQol 5-Dimension QoL Instrument (EQ-5D). Due to the early termination of the study, a simplified data analysis (primary endpoint and overall survival) was performed to fulfil the requirement from regulatory authorities for early termination studies. Therefore, no analyses were performed on this secondary efficacy endpoint.
Time Frame	Every 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Tasquinimod Pharmacokinetic (PK) Profile
Description	Tasquinimod PK profile: Following a single 1 mg dose of tasquinimod given to a subgroup of 12 Asian-Chinese patients (ancillary study). At steady state conditions based on limited sampling strategy. Following termination of the study the PK analyses were not performed.
Time Frame	Up to 216 hours after a single dose and during the double blind treatment period (Day 15, 29, 57 and 127)

Outcome Measure Data

Analysis Population Description

No data collected due to the early termination of the study. Therefore, no analyses performed on this secondary efficacy endpoint.

Arm/Group Title	Tasquinimod	Placebo
Arm/Group Description	One capsule (0.25, 0.50 or 1 mg), taken orally once a day with water and food (preferably the main evening meal). A patient initially received a 0.25 mg/day dose which was then titrated through 0.5 mg/day (from Day 15) to a maximum of 1 mg/day (from Day 29). If tolerability issues arose at 0.5 or 1 mg/day, patients had their dose reduced to 0.25 or 0.5 mg/day, respectively.	One capsule, taken orally once a day with water and food (preferably the main evening meal). Placebo capsules were identical to tasquinimod capsules in appearance and excipients but excluded the active compound (tasquinimod).
Measure Participants	0	0

Adverse Events

Time Frame	Adverse events (AEs) were monitored from informed consent until the date of death from any cause or 14 days after the last dose of study treatment, whichever came first, assessed up to 2 years.
Adverse Event Reporting Description	AEs were elicited by direct, non-leading questioning or by spontaneous reports. Natural progression/deterioration of the malignancy and death due to disease progression were to be recorded as part of the efficacy evaluation (not an AE/serious AE (SAE)). Non-serious AEs were not available. Therefore all TEAEs are presented Adverse Events section. Safety analyses were provided for the Double-Blind Period. Due to early termination, only 6 patients entered the Open-Label Period.
Arm/Group Title	Tasquinimod		Placebo
Arm/Group Description	One capsule (0.25, 0.50 or 1 mg), taken orally once a day with water and food (preferably the main evening meal). A patient initially received a 0.25 mg/day dose which was then titrated through 0.5 mg/day (from Day 15) to a maximum of 1 mg/day (from Day 29). If tolerability issues arose at 0.5 or 1 mg/day, patients had their dose reduced to 0.25 or 0.5 mg/day, respectively.		One capsule, taken orally once a day with water and food (preferably the main evening meal). Placebo capsules were identical to tasquinimod capsules in appearance and excipients but excluded the active compound (tasquinimod).
All Cause Mortality
	Tasquinimod		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	76/94 (80.9%)		30/50 (60%)
Serious Adverse Events
	Tasquinimod		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/94 (20.2%)		5/50 (10%)
Blood and lymphatic system disorders
Blood disorder	1/94 (1.1%)	1	0/50 (0%)	0
Cardiac disorders
Coronary artery disease	1/94 (1.1%)	1	0/50 (0%)	0
Ventricular extrasystoles	2/94 (2.1%)	2	0/50 (0%)	0
Gastrointestinal disorders
Nausea	1/94 (1.1%)	1	0/50 (0%)	0
General disorders
Death	1/94 (1.1%)	1	0/50 (0%)	0
Multi-organ failure	1/94 (1.1%)	1	0/50 (0%)	0
Hepatobiliary disorders
Bile duct stone	1/94 (1.1%)	1	0/50 (0%)	0
Hepatic failure	0/94 (0%)	0	1/50 (2%)	1
Infections and infestations
Influenza	1/94 (1.1%)	1	0/50 (0%)	0
Lung infection	1/94 (1.1%)	1	0/50 (0%)	0
Pneumonia	1/94 (1.1%)	1	1/50 (2%)	1
Injury, poisoning and procedural complications
Clavicle fracture	1/94 (1.1%)	1	0/50 (0%)	0
Femoral neck fracture	1/94 (1.1%)	1	0/50 (0%)	0
Subdural haemorrhage	1/94 (1.1%)	1	0/50 (0%)	0
Investigations
Weight decreased	1/94 (1.1%)	1	0/50 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/94 (1.1%)	1	0/50 (0%)	0
Diabetes mellitus	2/94 (2.1%)	2	0/50 (0%)	0
Gout	1/94 (1.1%)	1	0/50 (0%)	0
Type 2 diabetes mellitus	1/94 (1.1%)	1	0/50 (0%)	0
Musculoskeletal and connective tissue disorders
Bone pain	1/94 (1.1%)	1	0/50 (0%)	0
Intervertebral disc protrusion	1/94 (1.1%)	1	0/50 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system	0/94 (0%)	0	1/50 (2%)	1
Neoplasm progression	0/94 (0%)	0	1/50 (2%)	1
Nervous system disorders
Cerebral infarction	1/94 (1.1%)	1	0/50 (0%)	0
Radiculitis	1/94 (1.1%)	1	0/50 (0%)	0
Spinal cord compression	1/94 (1.1%)	1	0/50 (0%)	0
Psychiatric disorders
Anxiety disorder	1/94 (1.1%)	1	0/50 (0%)	0
Renal and urinary disorders
Haematuria	1/94 (1.1%)	1	1/50 (2%)	1
Urinary retention	0/94 (0%)	0	1/50 (2%)	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/94 (1.1%)	1	0/50 (0%)	0
Other (Not Including Serious) Adverse Events
	Tasquinimod		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	52/94 (55.3%)		19/50 (38%)
Blood and lymphatic system disorders
Anaemia	6/94 (6.4%)	6	2/50 (4%)	2
Gastrointestinal disorders
Abdominal distension	6/94 (6.4%)	7	0/50 (0%)	0
Constipation	6/94 (6.4%)	7	0/50 (0%)	0
Nausea	6/94 (6.4%)	6	3/50 (6%)	4
General disorders
Asthenia	5/94 (5.3%)	5	1/50 (2%)	2
Oedema peripheral	5/94 (5.3%)	5	0/50 (0%)	0
Infections and infestations
Upper respiratory tract infection	5/94 (5.3%)	5	2/50 (4%)	5
Investigations
Haemoglobin decreased	1/94 (1.1%)	1	3/50 (6%)	3
Metabolism and nutrition disorders
Decreased appetite	16/94 (17%)	18	2/50 (4%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	9/94 (9.6%)	9	4/50 (8%)	4
Back pain	14/94 (14.9%)	17	2/50 (4%)	2
Bone pain	5/94 (5.3%)	6	4/50 (8%)	4
Myalgia	9/94 (9.6%)	12	1/50 (2%)	1
Pain in extemity	6/94 (6.4%)	8	5/50 (10%)	5
Renal and urinary disorders
Dysuria	1/94 (1.1%)	1	3/50 (6%)	3

Limitations/Caveats

The study was terminated early due to the Sponsor deciding to stop development in prostate cancer; therefore, the results of all efficacy analyses should be considered exploratory and not supportive of efficacy in any indication.

More Information

Certain Agreements

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

The Sponsor required reasonable opportunity to review any abstract, presentation, or paper before the material was submitted for publication or communicated. This also applied to any amendments that were requested by referees or journal editors. The Sponsor committed to comment on the draft documents within a time period agreed in the contractual arrangements between the Sponsor and authors or their institution. Delays were also possible if publication would adversely affect patentability.