Trial Outcomes & Findings for Study Of Tasquinimod In Asian Chemo-Naïve Patients With Metastatic Castrate-Resistant Prostate Cancer (NCT NCT02057666)

NCT ID: NCT02057666

Last Updated: 2021-04-23

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 146 participants
• Primary outcome timeframe: 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
• Results posted on: 2021-04-23

Participant Flow

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.

229 patients were screened, of whom 146 were randomised (96 tasquinimod, 50 placebo).

Participant milestones

Measure	Tasquinimod 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.	Placebo 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).
Double Blind Treatment Period STARTED	96	50
Double Blind Treatment Period COMPLETED	0	6
Double Blind Treatment Period NOT COMPLETED	96	44
Open-Label Treatment Period STARTED	0	6
Open-Label Treatment Period COMPLETED	0	0
Open-Label Treatment Period NOT COMPLETED	0	6

Reasons for withdrawal

Measure	Tasquinimod 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.	Placebo 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).
Double Blind Treatment Period Withdrawal by Subject	8	5
Double Blind Treatment Period Poor tolerability	7	2
Double Blind Treatment Period Symptomatic disease progression	8	3
Double Blind Treatment Period Physician Decision	1	0
Double Blind Treatment Period Progressive disease for bone lesion	1	0
Double Blind Treatment Period Subject planning to withdraw	1	0
Double Blind Treatment Period Sponsor's request	70	34
Open-Label Treatment Period Poor tolerability	0	1
Open-Label Treatment Period Symptomatic disease progression	0	1
Open-Label Treatment Period Sponsor's request	0	4

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Tasquinimod n=96 Participants 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.	Placebo n=50 Participants 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 n=146 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants	9 Participants n=7 Participants	25 Participants n=5 Participants
Age, Categorical >=65 years	80 Participants n=5 Participants	41 Participants n=7 Participants	121 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	96 Participants n=5 Participants	50 Participants n=7 Participants	146 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	96 Participants n=5 Participants	50 Participants n=7 Participants	146 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment China	69 Participants n=5 Participants	34 Participants n=7 Participants	103 Participants n=5 Participants
Region of Enrollment Taiwan	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment Korea, Republic of	22 Participants n=5 Participants	11 Participants n=7 Participants	33 Participants n=5 Participants
Status of Visceral Metastases Presence	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Status of Visceral Metastases Absence	92 Participants n=5 Participants	48 Participants n=7 Participants	140 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Population: 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.

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.

Outcome measures

Measure	Tasquinimod n=96 Participants 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.	Placebo n=50 Participants 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).
Time to Radiological Progression-Free Survival (PFS)	11.00 months Interval 11.0 to The upper 95% confidence interval limit could not be calculated due to too few participants with events.	7.53 months Interval 5.67 to The upper 95% confidence interval limit could not be calculated due to too few participants with events.

SECONDARY outcome

Timeframe: From randomisation up to 3 years

Population: 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.

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

Outcome measures

Measure	Tasquinimod n=96 Participants 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.	Placebo n=50 Participants 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).
Overall Survival Number of censored observations	94 Participants	48 Participants
Overall Survival Number of deaths	2 Participants	2 Participants

SECONDARY outcome

Timeframe: 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

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

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 3 months

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Every 6 months during the follow-up period

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 216 hours after a single dose and during the double blind treatment period (Day 15, 29, 57 and 127)

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

Tasquinimod PK profile:

1. Following a single 1 mg dose of tasquinimod given to a subgroup of 12 Asian-Chinese patients (ancillary study).

2. At steady state conditions based on limited sampling strategy.

Following termination of the study the PK analyses were not performed.

Outcome measures

Outcome data not reported

Adverse Events

Tasquinimod

Serious events: 19 serious events

Other events: 52 other events

Deaths: 76 deaths

Placebo

Serious events: 5 serious events

Other events: 19 other events

Deaths: 30 deaths

Serious adverse events

Measure	Tasquinimod n=94 participants at risk 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.	Placebo n=50 participants at risk 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).
Blood and lymphatic system disorders Blood disorder	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.
Cardiac disorders Coronary artery disease	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.
Cardiac disorders Ventricular extrasystoles	2.1% 2/94 • Number of events 2 • 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. 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.	0.00% 0/50 • 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. 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.
Gastrointestinal disorders Nausea	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.
General disorders Death	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.
General disorders Multi-organ failure	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.
Hepatobiliary disorders Bile duct stone	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.
Hepatobiliary disorders Hepatic failure	0.00% 0/94 • 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. 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.	2.0% 1/50 • Number of events 1 • 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. 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.
Infections and infestations Influenza	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.
Infections and infestations Lung infection	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.
Infections and infestations Pneumonia	1.1% 1/94 • Number of events 1 • 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. 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.	2.0% 1/50 • Number of events 1 • 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. 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.
Injury, poisoning and procedural complications Clavicle fracture	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.
Injury, poisoning and procedural complications Femoral neck fracture	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.
Injury, poisoning and procedural complications Subdural haemorrhage	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.
Investigations Weight decreased	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.
Metabolism and nutrition disorders Decreased appetite	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.
Metabolism and nutrition disorders Diabetes mellitus	2.1% 2/94 • Number of events 2 • 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. 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.	0.00% 0/50 • 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. 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.
Metabolism and nutrition disorders Gout	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.
Metabolism and nutrition disorders Type 2 diabetes mellitus	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.
Musculoskeletal and connective tissue disorders Bone pain	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.00% 0/94 • 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. 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.	2.0% 1/50 • Number of events 1 • 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. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm progression	0.00% 0/94 • 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. 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.	2.0% 1/50 • Number of events 1 • 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. 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.
Nervous system disorders Cerebral infarction	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.
Nervous system disorders Radiculitis	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.
Nervous system disorders Spinal cord compression	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.
Psychiatric disorders Anxiety disorder	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.
Renal and urinary disorders Haematuria	1.1% 1/94 • Number of events 1 • 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. 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.	2.0% 1/50 • Number of events 1 • 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. 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.
Renal and urinary disorders Urinary retention	0.00% 0/94 • 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. 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.	2.0% 1/50 • Number of events 1 • 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. 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.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	1.1% 1/94 • Number of events 1 • 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. 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.	0.00% 0/50 • 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. 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.

Other adverse events

Measure	Tasquinimod n=94 participants at risk 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.	Placebo n=50 participants at risk 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).
Blood and lymphatic system disorders Anaemia	6.4% 6/94 • Number of events 6 • 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. 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.	4.0% 2/50 • Number of events 2 • 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. 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.
Gastrointestinal disorders Abdominal distension	6.4% 6/94 • Number of events 7 • 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. 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.	0.00% 0/50 • 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. 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.
Gastrointestinal disorders Constipation	6.4% 6/94 • Number of events 7 • 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. 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.	0.00% 0/50 • 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. 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.
Gastrointestinal disorders Nausea	6.4% 6/94 • Number of events 6 • 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. 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.	6.0% 3/50 • Number of events 4 • 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. 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.
General disorders Asthenia	5.3% 5/94 • Number of events 5 • 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. 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.	2.0% 1/50 • Number of events 2 • 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. 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.
General disorders Oedema peripheral	5.3% 5/94 • Number of events 5 • 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. 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.	0.00% 0/50 • 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. 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.
Infections and infestations Upper respiratory tract infection	5.3% 5/94 • Number of events 5 • 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. 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.	4.0% 2/50 • Number of events 5 • 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. 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.
Investigations Haemoglobin decreased	1.1% 1/94 • Number of events 1 • 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. 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.	6.0% 3/50 • Number of events 3 • 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. 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.
Metabolism and nutrition disorders Decreased appetite	17.0% 16/94 • Number of events 18 • 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. 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.	4.0% 2/50 • Number of events 2 • 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. 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.
Musculoskeletal and connective tissue disorders Arthralgia	9.6% 9/94 • Number of events 9 • 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. 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.	8.0% 4/50 • Number of events 4 • 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. 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.
Musculoskeletal and connective tissue disorders Back pain	14.9% 14/94 • Number of events 17 • 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. 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.	4.0% 2/50 • Number of events 2 • 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. 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.
Musculoskeletal and connective tissue disorders Bone pain	5.3% 5/94 • Number of events 6 • 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. 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.	8.0% 4/50 • Number of events 4 • 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. 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.
Musculoskeletal and connective tissue disorders Myalgia	9.6% 9/94 • Number of events 12 • 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. 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.	2.0% 1/50 • Number of events 1 • 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. 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.
Musculoskeletal and connective tissue disorders Pain in extemity	6.4% 6/94 • Number of events 8 • 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. 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.	10.0% 5/50 • Number of events 5 • 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. 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.
Renal and urinary disorders Dysuria	1.1% 1/94 • Number of events 1 • 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. 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.	6.0% 3/50 • Number of events 3 • 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. 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.

Additional Information

Medical Director, Oncology

Ipsen

Phone: clinical.trials@ipsen.com

Email: clinical.trials@ipsen.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
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