Clinical Trials List
Protocol Number8-55-58102-003
NCT Number(ClinicalTrials.gov Identfier)NCT02057666
2013-09-30 - 2017-10-31
Phase III
Terminated5
ICD-10C61
Malignant neoplasm of prostate
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9185
Malignant neoplasm of prostate
A Phase III, randomised, double-blind, placebo-controlled study of tasquinimod in Asian chemo-naïve patients with metastatic castrate resistant prostate cancer.
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Sponsor
IPSEN PHARMA
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/19
Investigators and Locations
Co-Principal Investigator
- Chuan-Shu Chen Division of Urology
- 熊小澐 Division of Radiology
- Cheng-Kuang Yang Division of Urology
- 林萬鈺 Division of Nuclear Medicine
- Shian-Shiang Wang Division of Urology
- Jian-Ri Li Division of Urology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Yi-Hsiu Huang Division of Urology
- 朱力行 Division of Nuclear Medicine
- Yen-Hwa Chang Division of Urology
- 沈書慧 Division of Radiology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 康智雄 Division of Urology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- - - Division of Urology
- - - Division of Urology
- Yeong-Shiau Pu Division of Urology
- Chia-Chi Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
metastatic castrate resistant prostate cancer
Objectives
Primary Study Objective:
To confirm the effect of tasquinimod on delaying disease progression
or death as compared with placebo in chemo-naïve patients with
metastatic castrate-resistant prostate cancer (mCRPC).
Secondary Study Objectives:
• To further evaluate the safety profile of tasquinimod
• To compare other clinical benefits (such as overall survival and
symptoms) of tasquinimod with placebo
• To evaluate the impact of tasquinimod on health related quality of
life (QoL)
• To determine the pharmacokinetics (PK) of tasquinimod.
Test Drug
Tasquinimod
Active Ingredient
Tasquinimod
Dosage Form
Capsule
Dosage
0.25、0.50 or 1mg
Endpoints
Primary Efficacy Endpoint(s):
The primary endpoint is radiological progression free survival (PFS)
defined as the time from the date of randomisation to the date of
radiological progression or death due to any cause.
Radiological progression is defined by any of the following criteria:
• Progression of soft tissue lesions evaluated by CT or MRI scan
according to RECIST v1.1 criteria
• Progression of bone lesions detected with bone scan according to
PCWG2 criteria
• Radiologically confirmed spinal cord compression or pathological
fracture due to malignant progression.
The primary endpoint will be centrally and independently evaluated.
Secondary Efficacy Endpoints:
• Overall survival, defined as the time from randomisation to death
due to any cause
• Radiological PFS based on local assessment, using the criteria as
defined for primary 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 occurs first
• Time from randomisation to further treatment for prostate cancer
• QoL measured by the Functional Assessment of Cancer Therapy
Prostate Module (FACT-P) questionnaire and by the EuroQol
5-Dimension QoL Instrument (EQ-5D)
• Tasquinimod PK profile:
(a) Following a single 1 mg dose of tasquinimod given to a
subgroup of 12 Asian-Chinese patients (ancillary study)
(b) At steady state conditions based on limited sampling strategy.
Safety Endpoints:
• Complete physical examination including the evaluation of
ECOG performance status, vital signs measurements and body
weight
• Electrocardiogram (ECG) findings
• Clinical laboratory assessments
• Adverse events (AEs).
Exploratory Endpoints:
• Time to radiological progression
• Time to symptomatic progression (including death due to prostate
cancer)
• Time to first radiological or symptomatic progression
• Time to first radiological or symptomatic progression or death
(due to any cause)
• Time to new soft tissue lesion
• Time to new bone lesion
• Time to PSA progression assessed by PSA Working Group
Criteria 2 (PSAWG2).
For patients with soft tissue lesions at randomisation:
• Time to progression of soft tissue lesions
• Response assessment for soft tissue lesions
For patients with bone metastases at randomisation:
• Time to progression of bone metastases
• Response assessment for bone metastases.
Pending feasibility, the following additional endpoints will be
explored:
• CTC enumeration
• Changes in biomarkers over time (i) vascular and disease
biomarkers (vascular endothelial growth factor [VEGF]a, VEGFc,
bone-specific alkaline phosphatase, soluble receptor for advanced
glycation end products and thrombospondin-1) and (ii) safety
biomarkers (interleukin [IL]-1 beta, IL-6, IL-8, tumour necrosis
factor alpha and complement 3a)
• Measurement of circulating immune and inflammatory cells (in a
subgroup of patients)
• Whole blood gene expression profiling.
The primary endpoint is radiological progression free survival (PFS)
defined as the time from the date of randomisation to the date of
radiological progression or death due to any cause.
Radiological progression is defined by any of the following criteria:
• Progression of soft tissue lesions evaluated by CT or MRI scan
according to RECIST v1.1 criteria
• Progression of bone lesions detected with bone scan according to
PCWG2 criteria
• Radiologically confirmed spinal cord compression or pathological
fracture due to malignant progression.
The primary endpoint will be centrally and independently evaluated.
Secondary Efficacy Endpoints:
• Overall survival, defined as the time from randomisation to death
due to any cause
• Radiological PFS based on local assessment, using the criteria as
defined for primary 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 occurs first
• Time from randomisation to further treatment for prostate cancer
• QoL measured by the Functional Assessment of Cancer Therapy
Prostate Module (FACT-P) questionnaire and by the EuroQol
5-Dimension QoL Instrument (EQ-5D)
• Tasquinimod PK profile:
(a) Following a single 1 mg dose of tasquinimod given to a
subgroup of 12 Asian-Chinese patients (ancillary study)
(b) At steady state conditions based on limited sampling strategy.
Safety Endpoints:
• Complete physical examination including the evaluation of
ECOG performance status, vital signs measurements and body
weight
• Electrocardiogram (ECG) findings
• Clinical laboratory assessments
• Adverse events (AEs).
Exploratory Endpoints:
• Time to radiological progression
• Time to symptomatic progression (including death due to prostate
cancer)
• Time to first radiological or symptomatic progression
• Time to first radiological or symptomatic progression or death
(due to any cause)
• Time to new soft tissue lesion
• Time to new bone lesion
• Time to PSA progression assessed by PSA Working Group
Criteria 2 (PSAWG2).
For patients with soft tissue lesions at randomisation:
• Time to progression of soft tissue lesions
• Response assessment for soft tissue lesions
For patients with bone metastases at randomisation:
• Time to progression of bone metastases
• Response assessment for bone metastases.
Pending feasibility, the following additional endpoints will be
explored:
• CTC enumeration
• Changes in biomarkers over time (i) vascular and disease
biomarkers (vascular endothelial growth factor [VEGF]a, VEGFc,
bone-specific alkaline phosphatase, soluble receptor for advanced
glycation end products and thrombospondin-1) and (ii) safety
biomarkers (interleukin [IL]-1 beta, IL-6, IL-8, tumour necrosis
factor alpha and complement 3a)
• Measurement of circulating immune and inflammatory cells (in a
subgroup of patients)
• Whole blood gene expression profiling.
Inclution Criteria
Each patient must meet all of the following criteria to be enrolled in this study:
(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 (computed tomography [CT] scan/magnetic
resonance imaging [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 have
been achieved, defined by any of the following criteria:
• Increasing serum PSA levels, with the most recent value ≥2 ng/mL
(increasing levels must be confirmed by three consecutive PSA
measurements, within 15 months prior to the start of study treatment.
The time between each PSA test should be preferably at least 14 days,
however a minimum of 7 days is acceptable. The third value will be 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).
(6) ECOG performance status of 0 or 1
(7) 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)
≤2.5 times ULN
• Serum amylase ≤ULN (if serum amylase >ULN, pancreatic amylase and
serum lipase should be analysed. If both pancreatic amylase and serum
lipase are >ULN, exclude patient).
(8) If sexually active with partner of childbearing potential, patient will agree to
use adequate contraceptive method (barrier contraceptive with spermicide)
while receiving study treatment and until 14 days after the stop of study
treatment or have been previously vasectomised
(9) No evidence (within last 5 years) of prior malignancies (except successfully
treated basal cell or squamous cell carcinoma of the skin)
(10) Able to swallow and retain oral medication
(11) Able to adhere to the study visit schedule and other protocol requirements
(12) 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
(13) 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.
(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 (computed tomography [CT] scan/magnetic
resonance imaging [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 have
been achieved, defined by any of the following criteria:
• Increasing serum PSA levels, with the most recent value ≥2 ng/mL
(increasing levels must be confirmed by three consecutive PSA
measurements, within 15 months prior to the start of study treatment.
The time between each PSA test should be preferably at least 14 days,
however a minimum of 7 days is acceptable. The third value will be 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).
(6) ECOG performance status of 0 or 1
(7) 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)
≤2.5 times ULN
• Serum amylase ≤ULN (if serum amylase >ULN, pancreatic amylase and
serum lipase should be analysed. If both pancreatic amylase and serum
lipase are >ULN, exclude patient).
(8) If sexually active with partner of childbearing potential, patient will agree to
use adequate contraceptive method (barrier contraceptive with spermicide)
while receiving study treatment and until 14 days after the stop of study
treatment or have been previously vasectomised
(9) No evidence (within last 5 years) of prior malignancies (except successfully
treated basal cell or squamous cell carcinoma of the skin)
(10) Able to swallow and retain oral medication
(11) Able to adhere to the study visit schedule and other protocol requirements
(12) 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
(13) 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
Patients meeting any of the following criteria will be excluded from the study:
(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 NCI-CTCAE v4.03
Grade ≤1. If radiation therapy is applied after Baseline scan, a new Baseline
scan needs 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 are allowed. Ongoing treatment should be kept
at a stable schedule; however, if medically required, a change of dose,
compound, or both is allowed
(5) Any treatment modalities involving major surgery within 4 weeks prior to the
start of study treatment
(6) Prostate cancer pain that requires ongoing treatment with narcotic analgesics
or warrants the initiation of radio- or chemotherapy
(7) Two or more of the following criteria:
• Gleason score ≥8
• Visceral metastasis
• Bone lesions both on and outside of the spinal axis.
(8) PSA >100 ng/mL
(9) Ongoing treatment with warfarin
(10) 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
(11) 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 is not allowed within 1 year
prior to the start of study treatment
(12) Ongoing treatment with sensitive CYP1A2 substrate or CYP1A2 substrate
with narrow therapeutic range at the start of study treatment
(13) Ongoing treatment with CYP3A4 substrate with narrow therapeutic range at
the start of study treatment
(14) 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
(15) 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
(16) History of pancreatitis
(17) Known brain or epidural metastases
(18) Known positive serology for human immunodeficiency virus (HIV) (patients
with known history of HIV will be excluded because of potential for
unforeseen toxicity and morbidity in an immunocompromised host)
(19) 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 have recovered from hepatitis will be allowed to enter
the study) with abnormal liver function
(20) 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 intend to complete
the entire course of that therapy)
(21) Any condition, including other active or latent infections, medical or
psychiatric conditions, or the presence of laboratory abnormalities, which
could confound the ability to interpret data from the study or places the
patient at unacceptable risk if he participates in the study
(22) Any patient who in the opinion of the Investigator should not participate in
the study.
(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 NCI-CTCAE v4.03
Grade ≤1. If radiation therapy is applied after Baseline scan, a new Baseline
scan needs 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 are allowed. Ongoing treatment should be kept
at a stable schedule; however, if medically required, a change of dose,
compound, or both is allowed
(5) Any treatment modalities involving major surgery within 4 weeks prior to the
start of study treatment
(6) Prostate cancer pain that requires ongoing treatment with narcotic analgesics
or warrants the initiation of radio- or chemotherapy
(7) Two or more of the following criteria:
• Gleason score ≥8
• Visceral metastasis
• Bone lesions both on and outside of the spinal axis.
(8) PSA >100 ng/mL
(9) Ongoing treatment with warfarin
(10) 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
(11) 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 is not allowed within 1 year
prior to the start of study treatment
(12) Ongoing treatment with sensitive CYP1A2 substrate or CYP1A2 substrate
with narrow therapeutic range at the start of study treatment
(13) Ongoing treatment with CYP3A4 substrate with narrow therapeutic range at
the start of study treatment
(14) 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
(15) 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
(16) History of pancreatitis
(17) Known brain or epidural metastases
(18) Known positive serology for human immunodeficiency virus (HIV) (patients
with known history of HIV will be excluded because of potential for
unforeseen toxicity and morbidity in an immunocompromised host)
(19) 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 have recovered from hepatitis will be allowed to enter
the study) with abnormal liver function
(20) 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 intend to complete
the entire course of that therapy)
(21) Any condition, including other active or latent infections, medical or
psychiatric conditions, or the presence of laboratory abnormalities, which
could confound the ability to interpret data from the study or places the
patient at unacceptable risk if he participates in the study
(22) Any patient who in the opinion of the Investigator should not participate in
the study.
The Estimated Number of Participants
-
Taiwan
30 participants
-
Global
300 participants
