Study Of Tasquinimod In Asian Chemo-Naïve Patients With Metastatic Castrate-Resistant Prostate Cancer
Condition: Prostatic Neoplasms, Castration-Resistant
MeSH terms: Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant
Intervention: Tasquinimod; Placebo
Intervention description: 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 capsules were identical to tasquinimod capsules in appearance and excipients but excluded the active compound (tasquinimod).
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 146.0
Sex: Male
Minimum age: 20 Years
Healthy volunteers: No
Keywords: CRPC; Metastatic; Chemotherapy naïve; Chemo-naïve; Prostate cancer; mCRPC; Chemotherapy-naïve; Chemo naïve

Summary:

      The primary objective was to confirm the effect of tasquinimod in delaying disease
      progression or death as compared with placebo in chemo-naïve patients with metastatic
      castrate-resistant prostate cancer (mCRPC).

      Secondary objectives included further evaluation of the safety profile of tasquinimod,
      comparison of clinical benefits (such as overall survival and symptoms) of tasquinimod with
      placebo, to evaluate the quality of life impact and to determine the pharmacokinetics of
      tasquinimod.
    

Eligibility criteria:

        Inclusion Criteria:

          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 (CT scan/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 had been
             achieved, defined by any of the following criteria:

               -  Increasing serum Prostate Specific Antigen (PSA) levels, with the most recent
                  value ≥2 ng/mL (increasing levels must have been confirmed by three consecutive
                  PSA measurements, within 15 months prior to the start of study treatment. The
                  time between each PSA test should have been preferably at least 14 days, however
                  a minimum of 7 days was acceptable. The third value was 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. Eastern Cooperative Oncology Group (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) ≤3 times ULN
                  (≤5 times ULN if liver metastases were present).

               -  Serum amylase ≤ULN (if serum amylase >ULN, pancreatic amylase and serum lipase
                  should have been analysed. If both pancreatic amylase and serum lipase were >ULN,
                  patient excluded).

          8. If sexually active with partner of childbearing potential, patient agreed to use
             adequate contraceptive method (barrier contraceptive with spermicide) while receiving
             study treatment and until 14 days after the stop of study treatment or had 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:

          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 National Cancer Institute (NCI)-Common Terminology Criteria for Adverse
             Events (CTCAE) version 4.03 Grade ≤1. If radiation therapy was applied after Baseline
             scan, a new Baseline scan needed 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 were allowed.
             Ongoing treatment was to be kept at a stable schedule; however, if medically required,
             a change of dose, compound, or both was allowed.

          5. Any treatment modalities involving major surgery within 4 weeks prior to the start of
             study treatment.

          6. Prostate cancer pain that required ongoing treatment with narcotic analgesics or
             warranted the initiation of radio- or chemotherapy.

          7. Both of the following criteria:

               -  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 was 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 were 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 had recovered from hepatitis were 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 have intended 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 have confounded
             the ability to interpret data from the study or placed the patient at unacceptable
             risk if he participated in the study.

         22. Any patient who in the opinion of the Investigator should not have participated in the
             study.