A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED PROOF OF CONCEPT STUDY OF MAINTENANCE THERAPY WITH TASQUINIMOD IN PATIENTS WITH METASTATIC CASTRATE-RESISTANT PROSTATE CANCER WHO ARE NOT PROGRESSING AFTER A FIRST LINE DOCETAXEL BASED CHEMOTHERAPY

• Register: EUCTR
• Last refreshed on: 17 August 2015
• Main ID: EUCTR2012-001038-32-IT
• Date of registration: 28/09/2012
• Prospective Registration: Yes
• Primary sponsor: IPSEN PHARMA SAS
• Public title: A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED PROOF OF CONCEPT STUDY OF MAINTENANCE THERAPY WITH TASQUINIMOD IN PATIENTS WITH METASTATIC CASTRATE-RESISTANT PROSTATE CANCER WHO ARE NOT PROGRESSING AFTER A FIRST LINE DOCETAXEL BASED CHEMOTHERAPY
• Scientific title: A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED PROOF OF CONCEPT STUDY OF MAINTENANCE THERAPY WITH TASQUINIMOD IN PATIENTS WITH METASTATIC CASTRATE-RESISTANT PROSTATE CANCER WHO ARE NOT PROGRESSING AFTER A FIRST LINE DOCETAXEL BASED CHEMOTHERAPY
• Date of first enrolment: 01/10/2012
• Target sample size: 140
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-001038-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Belgium, Czech Republic, Denmark, Germany, Hungary, Italy, Lithuania, Poland, Spain, United Kingdom

Contacts

• Name: VP Worldwide Clinical Development
• Affiliation: Ipsen Pharma

• Name: VP Worldwide Clinical Development
• Affiliation: Ipsen Pharma

Key inclusion & exclusion criteria

Inclusion criteria:
(1)Has provided written informed consent
(2)Histologically documented prostate cancer with evidence of
metastatic disease on radiological evaluation, with or without symptoms
(defined according to the brief pain inventory [BPI] scale, with use of
analgesics or narcotics)
(3)Has received a first line docetaxel based chemotherapy of 75 mg/m²
(as starting dose) every 3 weeks schedule of administration with
corticosteroids for a minimum of 6 cycles. Any combination with
investigational or non investigational agent is prohibited
(4)Male aged =18 years old
(5)Eastern Cooperative Oncology Group (ECOG) performance status of 0
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or 1
(6)Docetaxel-related adverse effects must have been resolved to NCICTCAE
v4.03 Grade =1. Chemotherapy-induced alopecia and Grade 2
peripheral neuropathy are allowed
(7)No progressive disease at the end of docetaxel treatment defined
according to RECIST criteria, no new lesion(s) assessed by bone scan
and no elevated PSA for the three last tests (with the first two PSA
values above or equal to the third PSA value). 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
(8)Last dose of docetaxel administered between 21 and 42 days before
randomisation
(9)Chemical or surgical castration verified by levels of serum
testosterone =50 ng/dL (1.75 nmol/L)
(10)A life expectancy of at least 12 weeks in the judgment of the
Investigator
(11)The following laboratory values within 7 days prior to
randomisation:
•Haematology
-Absolute granulocytes =1.5 x 109/L
-Platelets =100 x 109/L
-Haemoglobin =9 g/dL transfusions allowed, epoetin alfa allowed only if
last administration >2 weeks before randomisation
•Biochemistry
-Bilirubin =1.5 x upper limit of normal (ULN)
-Serum creatinine =1.5 x ULN or calculated creatinine clearance (CrCl)
using the Cockcroft-Gault formula =60 mL/min
-Alanine aminotransferase/ aspartate aminotransferase =3 x ULN (=5 x
ULN if liver metastases present)
(12)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
(13)Able to swallow and retain oral drug
(14)Able to adhere to the study visit schedule and other protocol
requirements
(15)Must be available for treatment, evaluation assessments and followup
at the study centres
(16)Able to comprehend the full nature and purpose of the study,
including possible risks and side effects, and to cooperate with the
Investigator and to comply with the requirements of the entire study.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 80

Exclusion criteria:
(1)Has concurrent use of other anticancer agents or treatm.,with the following exceptions:ongoing treatm. with luteinising hormonereleasing
hormone agonists or antagonists,denosumab or
bisphosphonate(e.g.zoledronic acid)is permitted if started =4weeks
prior to Screening.Ongoing treat. should be kept at a stable dose
regimen(2)Has ongoing treatment with warfarin(3)Had prior radiation therapy since starting docetaxel.Exceptions may
be made for palliative non-myelosuppressive radiation therapy
administered more than 2 weeks prior to randomisation(4)Had prior strontium,samarium or radium therapy or prior treat.with tasquinimod,or any agents with antiangiogenic properties
(5)Has ongoing treat.with corticosteroids at>10mg/day
prednisolone equivalent(6)Has prostate cancer pain that warrants the initiation of radiotherapy
or chemotherapy(7)Has known hypersensitivity to the study treatment,to any of its
excipients or treatments with a similar chemical structure(8)Has ongoing treatment with cytochrome P450(CYP)1A2 orCYP3A4
metabolised drug substance with narrow therapeutic range at the start
of study treatment(9)Has a systemic exposure to ketoconazole or other strong CYP3A4
isozyme inhibitors or inducers within 14 days prior to the start of study
treatment.Systemic exposure to amiodarone is not permitted within 1year prior to the start of study treatment(10)Has simultaneous participation in any other study involving treatment with investigational drugs or device or has received treatment
with investigational drugs less than 4weeks prior to randomisation
(11)Has myocardial infarction,percutaneous coronary intervention,acute coronary syndrome,coronary artery bypass graft,New York Heart
Association (NYHA)classIII/IV congestive heart failure,cerebrovascular accident,transient ischaemic attack,or limb
claudication at rest,within 6 months prior to randomis.and ongoing
symptomatic dysrhythmias,unstable angina,uncontrolled hypert.
and uncontrolled atrial or ventricular arrhythmias
(12)Has history of pancreatitis
(13)Has known brain or epidural metastases.Pts with previous
medullary cord compression without any neurol.deficit could be
included(14)Has known posit.serology for human immunodeficiency virus
(15)Has chronic hepat.with advanced,decompensated hepatic
disease,cirrhosis of the liver,history of a chronic viral hepatitis or
known viral hepatitis carrier(pts who have recovered from
hepatitis will be permitted to enter the study)(16)Has active tuberculosis(TB),or with known, untreated latent TB.
Country-specific TB therapy should have been given for at least 30days
prior to the start of study treatment and patient should intend to
complete the entire course of that therapy
(17)Has any condition,including other active or latent infections,medical or psychiatric conditions,or the presence of clinically significant
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
(18)Should not participate in the study in the opinion of the Investigator
(19)Is currently receiving immunosuppressive therapy
(20)Has a history of major surgery 4 weeks prior to randomisation,or
has an incompletely healed surgical incision
(21)Has a history of other malignancies,except adequately treated nonmelanoma
skin cancer or other solid tumours curatively treated,without
evidence of disease for>5years
(22)Is deprived of his freed

Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

maintenance therapy in metastatic Castrate Resistant Prostate Cancer patients who are not progressing under/after a first line docetaxel based chemotherapy
MedDRA version: 15.0 Level: SOC Classification code 10029104 Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps) System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: tasquinimod
Product Code: ABR-215050
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: tasquinimod
CAS Number: 254964-60-8
Current Sponsor code: ABR-215050
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: .25-1
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To compare other clinical benefits (such as overall survival, PFS on nextline
therapy [PFS 2] and symptoms) of tasquinimod with placebo
To evaluate the impact of tasquinimod on health related quality of life
(QoL)
To further characterise the pharmacokinetics (PK) of tasquinimod using
a population approach.

Main Objective: To compare the clinical efficacy (i.e. radiological progression free
survival [PFS]) of tasquinimod maintenance therapy with placebo in
patients with metastatic castrate-resistant prostate cancer (mCRPC)
who have not progressed after a first line docetaxel based
chemotherapy.

Primary end point(s): The primary endpoint is radiological PFS including skeleton related
events, defined as the time from the date of randomisation to the date of
radiological progression or death due to any cause.

Timepoint(s) of evaluation of this end point: assessment every 8 weeks until radiological progression

Secondary Outcome(s)

Secondary end point(s): • Overall survival, defined as the time from randomisation to death due
to any cause
• Symptomatic PFS, defined as the time from the date of randomisation
to the date of symptomatic progression or death due to prostate cancer,
whichever occurs first (symptomatic progression as assessed by Pain
BPI and analgesic use)
• 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)
• PK measurements of tasquinimod.
• PFS on next-line therapy (PFS 2)
• Complete physical examination including the evaluation of
performance status (ECOG), vital signs measurements and body weight
• Electrocardiogram findings
• Clinical laboratory assessments
• Adverse events.

Timepoint(s) of evaluation of this end point: Please see schedule of assessment (pages 10-12 of the protocol)

Secondary ID(s)

8-55-58102-002

2012-001038-32-ES

Source(s) of Monetary Support

Ipsen Pharma