Adding Mitomycin C to Bacillus of Calmette-Guerin (BCG) as Adjuvant Intravesical Therapy for High-risk, Non-Muscle-invasive Bladder Cancer: a Randomised Phase 3 Trial

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Adding Mitomycin C to Bacillus of Calmette-Guerin (BCG) as Adjuvant Intravesical Therapy for High-risk, Non-Muscle-invasive Bladder Cancer: a Randomised Phase 3 Trial

Condition: Bladder Cancer

Intervention:

  • Biological: Bacillus of Calmette-Guerin (BCG)
  • Drug: Mitomycin C (MMC)

Purpose: Open label, randomised phase 3 trial of the addition of Mitomycin C to BCG as adjuvant intravesical therapy for high-risk, non-muscle-invasive bladder cancer. The study aim is to compare disease-free survival between treatment arms: BCG alone versus Mitomyicn C in addition to BCG.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02948543

Sponsor: University of Sydney

Primary Outcome Measures:

  • Measure: Disease free survival (death or recurrence)
  • Time Frame: Up to 5 years
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Activity (Clear cystoscopy at 3 months)
  • Time Frame: At 3 months after patient randomised
  • Safety Issue:
  • Measure: Time to recurrence (recurrence)
  • Time Frame: Up to 5 years
  • Safety Issue:
  • Measure: Time to progression (disease progression)
  • Time Frame: Up to 5 years
  • Safety Issue:
  • Measure: Safety (Adverse events graded according to CTC AE V4.0)
  • Time Frame: Measured before day 1 of each instillation during treatment.
  • Safety Issue:
  • Measure: Health-Related Quality of Life
  • Time Frame: Up to 5 years
  • Safety Issue:
  • Measure: Overall survival time (death from any cause)
  • Time Frame: Up to 5 years
  • Safety Issue:
  • Measure: Treatment Completion
  • Time Frame: Measured at end of study treatment (12 months after patient randomized).
  • Safety Issue:
  • Measure: Marginal resource use
  • Time Frame: 5 years after last patient randomized (or date last patient has died, whichever sooner).
  • Safety Issue:

Estimated Enrollment: 500

Study Start Date: July 2013

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  1. Males or females with confirmed high grade pTa or stage pT1 (any grade) non-muscle invasive bladder cancer on initial or re-resection histology (concurrent carcinoma in situ is allowed).
  2. Age >= 18 yrs
  3. No macroscopically visible disease at cystoscopy within 8 weeks prior to randomisation. This may be either the initial Transurethral Resection of the Bladder Tumour (TURBT) at which the primary tumour was completely resected, or a planned second cystoscopy and/or re-resection done within 8 weeks of the initial TURBT.
  4. ECOG Performance Status of 0-2
  5. Adequate bone marrow function
  6. Adequate renal function
  7. Adequate liver function
  8. Study treatment both planned and able to start within 4 weeks of randomisation
  9. Has completed the HRQL questionnaires or is unable to complete them because of literacy, insufficient English or limited vision
  10. Willing and able to comply with all study requirements, including treatment, timing and/or nature of all required assessments
  11. Signed, written informed consent

Exclusion Criteria:

  1. Contraindications or hypersensitivity to investigational products, BCG and Mitomycin C
  2. Prior treatment with any other intravesical agent including BCG or Mitomycin C (excludes single doses given post TURBT)
  3. Current or past transitional cell carcinoma (TCC) of the upper urinary tract
  4. Prior muscle-invasive (stage T2 or higher) transitional-cell carcinoma of the bladder
  5. Bladder dysfunction precluding intravesical therapy eg. Severe urinary incontinence or overactive or spastic bladder
  6. Life expectancy < 3 months
  7. Congenital or acquired immune deficiencies, whether due to a concurrent disease (e.g. acquired immune deficiency syndrome (AIDS), leukaemia, lymphoma) or immunosuppressive therapy (e.g. corticosteroids), or cancer therapy (cytotoxic drugs, radiation)
  8. Prior radiotherapy of the pelvis
  9. Prior or current treatment with radiotherapy-response or biological-response modifiers
  10. Clinical evidence of existing active tuberculosis
  11. History of another malignancy within 5 years prior to registration. Patients with non-melanomatous carcinoma of the skin are eligible for this study.
  12. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol.
  13. Pregnancy, lactation, or inadequate contraception. Women must be post menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilised or use a (double if required) barrier method of contraception.

Contact:

  • BCG+MMC Trial Coordinator
  • +61 2 9562 5000

Locations:

  • Concord Repatriation General Hospital
  • Concord New South Wales 2139 Australia
  • Northern Cancer Institute, St Leonards
  • St Leonards New South Wales 2065 Australia
  • The Tweed Hospital
  • Tweed Heads New South Wales 2485 Australia
  • Sydney Adventist Hospital
  • Wahroonga New South Wales 2076 Australia
  • Footscray Hospital
  • Footscray Victoria 3011 Australia
  • Frankston Hospital
  • Frankston Victoria 3199 Australia
  • Austin Health – Austin Hospital
  • Heidelberg Victoria 3084 Australia
  • The Alfred Hospital
  • Melbourne Victoria 3004 Australia
  • Royal Melbourne Hospital – City Campus
  • Parkville Victoria 3050 Australia
  • Fiona Stanley Hospital
  • Murdoch Western Australia 6150 Australia

View trial on ClinicalTrials.gov

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