Study to Assess the Efficacy of Brachytherapy With or Without Hormone Therapy, Using Triptorelin 22.5mg in Patients With Recurrence of Prostate Cancer
Condition: Prostate Cancer
MeSH terms: Prostatic Neoplasms; Recurrence
Intervention: Triptorelin 22.5 mg; Brachytherapy
Intervention description: Triptorelin: A single, intramuscular injection (22.5 mg), preferably 2 months before brachytherapy.; Brachytherapy: Low or high dose rate.
Intervention MeSH terms: Triptorelin Pamoate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: Male
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Recurrent Prostate Carcinoma; Brachytherapy; Triptorelin; Hormone Therapy

Summary:

      The primary objective of the study was to compare the efficacy of brachytherapy versus
      brachytherapy + triptorelin 22.5 mg (single injection) in subjects with recurrence of
      prostate cancer previously treated with radiotherapy. Efficacy was to be assessed by
      biochemical failure-free survival (BFFS) curves from treatment initiation up to 5 years.

      Secondary objectives included comparing the following: the differences in time to progression
      of subjects receiving brachytherapy + triptorelin 22.5 mg versus subjects receiving
      brachytherapy only, the BFFS percentages between both treatment groups at 5 years from
      treatment initiation, overall survival between both treatment groups, total testosterone
      changes (from baseline visit up to 12 months) and Prostate Specific Antigen (PSA) levels
      (from baseline visit up to 60 months of treatment) between both treatment groups, quality of
      life (QoL) modifications (Spanish version of the Expanded Prostate Cancer Index Composite
      (EPIC) questionnaire) between the baseline score and the rest of measurements, and to compare
      safety between both treatment groups.
    

Eligibility criteria:

        Inclusion Criteria:

          1. A history of prostate cancer (T1-T2-T3 N0 M0), confirmed through histopathology and
             initially treated with radiotherapy.

          2. Age ≤ 75 years.

          3. Biochemical failure due to Phoenix criteria (nadir + 2) and local recurrence of the
             initial prostate cancer, confirmed by prostate biopsy, with neither regional
             involvement nor distant metastases.

          4. Late local recurrence of the initial prostate cancer. A recurrence is late when it
             appears after longer than 18 months post-radiotherapy.

          5. PSA < 10 ng/mL at the time of recurrence.

          6. The subject was required to be amenable to brachytherapy treatment.

          7. Adequate urinary function according to the questionnaire (IPSS ≤ 20 points).

          8. Suitable bone marrow function, determined by:

               -  Haemoglobin > 10 g/dL.

               -  Neutrophil count > 1.5 x 10^9/L.

               -  Platelet count > 100 x 10^9/L.

          9. Suitable liver function determined by: serum bilirubin < 1.5 x Upper Normal Level
             (UNL), and alanine aminotransferase (ALT) or aspartate aminotransferase (AST) <
             2.5xUNL.

         10. Suitable renal function determined by: serum creatinine < 1.5 x UNL, or creatinine
             clearance ≥ 60 mL/min.

         11. The subject was required to be ≥ 18 years old.

         12. The subject had to give his written informed consent (personally signed and dated)
             before starting with any study-related procedure.

         13. Life expectancy > 5 years.

        Exclusion Criteria:

          1. Evidence of metastatic disease.

          2. Previous evidence of hormone-resistant cancer.

          3. Lack of availability for performing regular follow-up.

          4. Subjects who were receiving or had received either luteinizing hormone-releasing
             hormone (LH-RH) agonists, or antagonists, over the previous 12 months.

          5. Subjects who had been on treatment with other hormone therapies, including
             antagonists, megestrol acetate, finasteride, dutasteride, any herbaceous product known
             to reduce the PSA levels, or any systemic corticosteroid, over the previous 4 weeks.

          6. Subjects who had previously undergone a radiotherapy treatment that was completed
             within 18 months of inclusion.

          7. Subjects with pre-existing heart failure (New York Heart Association class III or IV),
             or with a myocardial infarction within 6 months of inclusion.

          8. Subjects with a significant co-existing disease or an active infection.

          9. Subjects who had been treated with investigational therapies within 4 weeks prior to
             the brachytherapy ± triptorelin treatment.

         10. Subjects with known hypersensitivity to triptorelin, LH-RH, other LH-RH-analogous
             agonists, or any excipients in triptorelin 22.5 mg.

         11. Subjects with a mental condition that prevented them from understanding the nature,
             the scope and the potential consequences of this study, and/or subjects who showed an
             uncooperative attitude.