E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
maintenance therapy in metastatic Castrate Resistant Prostate Cancer patients who are not progressing under/after a first line docetaxel based chemotherapy |
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E.1.1.1 | Medical condition in easily understood language |
maintenance therapy in metastatic Castrate Resistant Prostate Cancer patients who are not progressing under/after a first line docetaxel based chemotherapy |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 PSA3≤PSA2≤PSA1. 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.
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E.4 | Principal 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 incision
(21)Has a history of other malignancies, except adequately treated non-melanoma skin cancer or other solid tumours curatively treated, without evidence of disease for >5 years
(22)Is deprived of his freedom or rights by virtue of an order issued either by any judicial or administrative authorities, is unable to express his consent, or is committed to a health institution for reasons other than the study
(23)Has a history of, or known current, problems with drug or alcohol abuse
(24)Has any mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study and/or evidence of an uncooperative attitude.
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
assessment every 8 weeks until radiological progression |
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E.5.2 | 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.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Please see schedule of assessment (pages 10-12 of the protocol) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study will be considered to have finished (end of study) when 80% of the patients have died or 2 years after the last patient randomised, whichever occurs last. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |