Cis-urocanic Acid (Cis-UCA) in Patients With Primary or Recurrent Non-muscle Invasive Bladder Cancer

This study has been completed.
Sponsor:
Collaborators:
Turku University Hospital
Tampere University Hospital
FinnMedi Oy
Information provided by (Responsible Party):
BioCis Pharma Ltd
ClinicalTrials.gov Identifier:
NCT01458847
First received: October 4, 2011
Last updated: November 9, 2012
Last verified: November 2012
  Purpose

The purpose of this study is to evaluate safety, tolerability and pharmacokinetics of intravesical cis-urocanic acid in patients with primary or recurrent non-muscle invasive bladder cancer.


Condition Intervention Phase
Non-muscle Invasive Bladder Cancer
Drug: cis-UCA solution
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single Dose, Dose-escalating, Phase I Study to Evaluate Safety, Tolerability and Pharmacokinetics of Intravesical Cis-urocanic Acid (Cis-UCA) in Patients With Primary or Recurrent Non-muscle Invasive Bladder Cancer

Resource links provided by NLM:


Further study details as provided by BioCis Pharma Ltd:

Primary Outcome Measures:
  • Bladder-related AEs [ Time Frame: until resection, max 2 months ] [ Designated as safety issue: Yes ]
  • Urinalysis [ Time Frame: participants will be followed until resection, an expected average of 2 months ] [ Designated as safety issue: Yes ]
  • Evaluation of the appearance of normal bladder epithelium after the cis-UCA dose by cystoscopy during the planned surgical procedure [ Time Frame: participants will be followed until resection, an expected average of 2 months ] [ Designated as safety issue: Yes ]
    cystoscopy descriptions


Secondary Outcome Measures:
  • Area Under Curve (AUC) [ Time Frame: Predose, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, and 24 h post-dose ] [ Designated as safety issue: No ]
  • Efficacy [ Time Frame: Predose, up to 2 months post-dose ] [ Designated as safety issue: No ]
    Change in tumor size from baseline by cystoscopy, change in tumor proliferation marker Ki-67 by immunohistochemistry, change in caspase-3 expression by immunohistochemistry


Enrollment: 12
Study Start Date: October 2009
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort I: 2% cis-UCA solution (50 ml) Drug: cis-UCA solution
Cohort I: 2% cis-UCA solution (50 ml); min 3, max 12 patients
Experimental: Cohort II: 4% cis-UCA solution (50 ml) Drug: cis-UCA solution
Cohort II: 4% cis-UCA solution (50 ml); min 0, max 12 patients
Experimental: Cohort III: 6% cis-UCA solution (50 ml) Drug: cis-UCA solution
Cohort III: 6% cis-UCA solution (50 ml); min 0, max 12 patients

Detailed Description:

This is a single dose, dose-escalating, Phase I study to evaluate safety, tolerability and pharmacokinetics of intravesical cis-urocanic acid (cis-UCA) in patients with primary or recurrent non-muscle invasive bladder cancer.

The primary objectives is to evaluate safety and tolerability of cis-UCA after a single intravesical instillation with escalating doses and to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of cis-UCA after a single intravesical instillation with escalating doses.

The secondary objectives are to evaluate pharmacokinetics of cis-UCA after a single intravesical instillation with escalating doses, to obtain preliminary information on possible anti-tumor effects of cis-UCA by cystoscopy and histological evaluation after a single intravesical instillation with escalating doses, and to evaluate the effects of cis-UCA on different surrogate biochemical markers on tumor growth and differentiation after a single intravesical instillation with escalating doses.

The key eligibility criteria are the following: Patients with primary or recurrent non-muscle invasive bladder cancer; eligible for intravesical treatment; age 18-80 years; WHO performance status 0-2; acceptable liver, renal and hematological function within 30 days prior to inclusion.

At minimum 3 patients and at maximum 24 patients is planned to be included in the study. The fixed dose-escalation levels will be used.

Up to three dose cohorts are planned to be included:

  • Cohort I: 2% cis-UCA solution (50 ml); min 3, max 12 patients
  • Cohort II: 4% cis-UCA solution (50 ml); min 0, max 12 patients
  • Cohort III: 6% cis-UCA solution (50 ml); min 0, max 12 patients
  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Informed consent obtained prior to any screening procedures
  2. Patients with primary or recurrent non-muscle invasive bladder cancer
  3. The patient is eligible for intravesical instillation
  4. Age 18-80 years
  5. WHO performance status 0-2
  6. Body weight at least 50 kg for males and 45 kg for females; body mass index (BMI) 18-35 kg/m2
  7. Diagnostic cystoscopy performed within 30 days prior to screening visit
  8. Negative pregnancy test (premenopausal female patients) at screening and use of adequate contraceptive measures (both male and female patients) throughout the study and 30 days after the cis-UCA dose oPremenopausal female volunteers should be either surgically sterile or using a reliable contraception method: intrauterine device (hormonal or non-hormonal); oral combination pill or hormonal contraception patch; or two of the following: intra-vaginal hormonal ring, oral contraceptive containing progestin only, spermicidal foam, condom, sterilization of male sexual partner (surgical vasectomy) oPatients with no current heterosexual relationship may be included according to the judgment of the Investigator oIf menopause occurred 2 years ago at the minimum, no contraception is required for female participants, nor pregnancy tests oReliable contraception for male patients is concordant with above listed methods for females, as applicable
  9. Acceptable liver function, renal function and hematological status at screening
  10. Urinalysis showing no clinically significant abnormalities except those attributable for bladder cancer

Exclusion Criteria:

  1. Previously diagnosed bladder fibrosis
  2. Total bladder capacity estimated by cystoscopy to be less that 150 ml
  3. Urinary incontinence of that severity that according to the opinion of the Urologist/Investigator would compromise the ability of the patient to retain the study drug intravesical instillation for one hour
  4. Severe irritative voiding symptoms, such as urgency, frequency and nocturia that could compromise protocol objectives in the opinion of the Urologist/Investigator
  5. Serious disease (e.g., hydronephrosis, renal or liver failure or other condition) that could compromise protocol objectives in the opinion of the Urologist/Investigator
  6. Active, uncontrolled bacterial, viral, or fungal infections, including urinary tract infection
  7. Previous treatment with radiotherapy, or systemic chemotherapy.
  8. Intravesical instillation(s) within 6 months with BCG or cytostatic agents
  9. Known allergy to cis-UCA-instillation solution (see Section 5.1 for excipients).
  10. Having participated in a clinical study with cis-UCA previously
  11. Known any serious immunodeficiency condition
  12. Donation of blood or participation in another drug study within 60 days (males) or 90 days (females) before the intravesical instillation in this study
  13. Any clinically significant laboratory test result (including positive tests for HIV and hepatitis B or C) according to Investigator/Urologist
  14. Excessive use of alcohol (on average more than 24 units per week for males, and more that 16 units per weeks for females; unit = 4 cl spirits or equivalent)
  15. Clinically significant illness (except bladder cancer) within 30 days before the screening visit or any other condition, such as vesicourethral reflux (VUR), or complicated urinary stone disease that in the opinion of the Investigator would interfere with the evaluation of the study results or constitute a health hazard for the patient
  16. Regular use of urine alkalinizing agents/drugs (e.g., acetazolamide, calcium phosphates, aluminium hydroxide, sodium bicarbonate, sodium carbonate, sodium citrate, potassium citrate) that might interfere with the evaluation of the study results
  17. Unwillingness or doubtful capacity to comply with the protocol
  18. Doubtful availability, in the opinion of the Investigator, to complete the study
  19. Poor peripheral venous access -
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01458847

Locations
Finland
Tampere University Hospital, Department of Urology
Tampere, Finland, 33520
Turku University Hospital, Department of Surgery, Division of Urology
Turku, Finland, 20520
Sponsors and Collaborators
BioCis Pharma Ltd
Turku University Hospital
Tampere University Hospital
FinnMedi Oy
Investigators
Principal Investigator: Juha Peltonen, MD CRST (Clinical Research Services Turku)
Study Chair: Liisa Pylkkänen, MD, PhD BioCis Pharma Ltd
  More Information

No publications provided

Responsible Party: BioCis Pharma Ltd
ClinicalTrials.gov Identifier: NCT01458847     History of Changes
Other Study ID Numbers: CL08003, 2009-011287-11
Study First Received: October 4, 2011
Last Updated: November 9, 2012
Health Authority: Finland: Finnish Medicines Agency

Keywords provided by BioCis Pharma Ltd:
bladder cancer
cis-urocanic acid
primary
recurrent
non-muscle

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
Pharmaceutical Solutions
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014