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: 4 August 2015
• Main ID: EUCTR2012-001038-32-GB
• Date of registration: 06/11/2012
• Prospective Registration: Yes
• Primary sponsor: Ipsen Pharma
• 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 - Maintenance Therapy with Tasquinimod in patients with mCRPC
• Date of first enrolment: 05/02/2013
• 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:
All patients must fulfil the following criteria to participate in the study:
(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 (as a monotherapy)every 3 weeks schedule of administration with corticosteroids for a minimum of 6 cycles with a cumulative dose = 360 mg/m2. Any combination with investigational or non investigational agent is prohibited
(4)Male aged =18 years old
(5)Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
(6)Docetaxel-related adverse effects must have been resolved to NCI-CTCAE 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.
Note: PSA value can be rounded to the nearest whole number if PSA>10 ng/mL. If the PSA3 value is above the PSA2, a fourth PSA test will be performed. The PSA4 value should be below or equal to PSA2
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 14 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 follow-up 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 0
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
A patient will not be included in the study if he:
(1)Has concurrent use of other anticancer agents or treatments, with the following exceptions: ongoing treatment with luteinising hormone-releasing hormone agonists or antagonists, denosumab or bisphosphonate (e.g. zoledronic acid) is permitted if started =4 weeks prior to Screening. Ongoing treatment should be kept at a stable dose regimen
(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 treatment with tasquinimod, or any agents with antiangiogenic properties
(5)Has ongoing treatment with corticosteroids at >10 mg/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 or CYP3A4 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 1 year 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 4 weeks prior to randomisation
(11)Has 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 randomisation, has 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
(12)Has history of pancreatitis
(13)Has known brain or epidural metastases. Patients with previous medullary cord compression without any neurological deficit could be included
(14)Has known positive serology for human immunodeficiency virus
(15)Has chronic hepatitis with advanced, decompensated hepatic disease, cirrhosis of the liver, history of a chronic viral hepatitis or known viral hepatitis carrier (patients 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 30 days 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 i

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

Health Condition(s) or Problem(s) studied

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

maintenance therapy in metastatic Castrate Resistant Prostate Cancer patients who are not progressing under/after a first line docetaxel based chemotherapy

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: 0.25-1
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

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.

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.

Secondary Objective: -To further evaluate the safety profile of tasquinimod
-To compare other clinical benefits (such as overall survival, PFS on next-line 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.

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)

2012-001038-32-ES

8-55-58102-002

Source(s) of Monetary Support

Ipsen Pharma