Intravesical Photodynamic Therapy (PDT) in BCG Refractory High-Risk Non-muscle Invasive Bladder Cancer (NMIBC) Patients
Verified February 2017 by Theralase Inc.
Sponsor:
Collaborators:
University Health Network, Toronto
Medelis Inc.
WCCT Global
Information provided by (Responsible Party):
Theralase Inc.
ClinicalTrials.gov Identifier:
NCT03053635
First received: February 6, 2017
Last updated: February 23, 2017
Last verified: February 2017
This is a phase Ib, open-label, single-arm, single-center study conducted in Canada. Subjects with NMIBC (Ta, T1, and/or Tis) who are not candidates for or have refused radical cystectomy will be eligible for participation in the study. BCG intolerance or refractory disease are defined as inability to tolerate or failure to achieve a tumour-free state after at least one induction (a minimum of 5 instillations) followed by either a second induction (a minimum of 5 instillations) or at least 2 maintenance instillations. Subjects experiencing disease relapse within 12 months or less after finishing the second course of BCG therapy are also considered refractory. The study will consist of 2 phases. In the first phase, 3 subjects will receive PDT (TLC-3200 System) employing 0.35 mg/cm^2 (maximum recommended starting dose) TLD1433. If treatment with the maximum recommended starting dose does not raise significant safety concerns as determined by the safety monitoring committee, an additional 6 subjects will receive PDT with 0.70 mg/cm^2 (therapeutic dose) TLD1433.
| Non-Muscle Invasive Bladder Cancer (NMIBC) Refractory to BCG | Drug: TLD1433 infusion and photodynamic therapy (PDT) treatment | Phase 1 |
| | |
| Study Type: | Interventional |
| Study Design: | Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment |
| Official Title: | A Phase Ib Trial of Intravesical Photodynamic Therapy in Patients With Non-muscle Invasive Bladder Cancer at High Risk of Progression Who Are Refractory to Bacillus Calmette-Guerin Therapy and Who Are Medically Unfit for/Refuse Cystectomy |
Primary Outcome Measures:
- Assessment of Safety: Evaluation of the safety of TLD1433 will be assessed with the incidence and severity of Adverse Effects [ Time Frame: Up to the completion of follow-up phase (180 days) ]
Hematology, blood chemistry, and urinalysis for safety purposes will be performed at days 1, 3, 30, 60, 90 and 180 as well as at the time of premature discontinuation. Troponin testing will only be performed at day 1, 3, and 30.
CT scan will be performed at Day 30 and Day 180 to identify possible tissue reaction to PDT.
ECG will be performed at baseline, during the study treatment and Day 1 (24 hours) after study treatment. An additional ECG will be performed at 8 hours ± 15 minutes post-drug instillation to correspond with the 8 hour PK blood sample at Day 0.
Vital signs (blood pressure, heart rate, respiratory rate and temperature) will be recorded for safety purposes at every visit throughout treatment and at the end of study.
A comprehensive physical examination for safety purposes is required during Screening and at the Month 6/End of Study and End of Treatment.
Multiple measurements will be aggregated into number of abnormal results different from baseline for each subject.
Secondary Outcome Measures:
- Pharmacokinetics of TLD1433 in blood and urine (Cmax) [ Time Frame: Blood (prior to drug, 1h, 4h, 8h, 24h, and 72h post drug). Urine (prior to drug, 8h, 24h, and 72h post drug) ]
Pharmacokinetics (PK) of TLD1433 will be assessed with the maximum observed concentration (Cmax) in blood and urine.
- Pharmacokinetics of TLD1433 in blood and urine (area under curve) [ Time Frame: Blood (prior to drug, 1h, 4h, 8h, 24h, and 72h post drug). Urine (prior to drug, 8h, 24h, and 72h post drug) ]
Pharmacokinetics (PK) of TLD1433 will be assessed with the area under the curve from time zero to the last quantifiable concentration (AUC0-t) in blood and urine.
Other Outcome Measures:
- Efficacy: Recurrence is defined as the interval from Day 0 to documented recurrence [ Time Frame: The overall efficacy will be evaluated during the course of the study (at 3 and 6 months) ]
Recurrence is defined as any new tumour growth, i.e. any biopsy-confirmed new or recurrent tumour, or positive saline bladder washing cytology.
Recurrence endpoint is either:
- Recurrence-free survival rate at 3 and 6 months.
- Recurrence rate at 3 and 6 months.
- Efficacy: Survival is defined as the interval from Day 0 to documented survival or death of any cause. [ Time Frame: The overall survival will be evaluated during the course of the study (at 3 and 6 months) ]
Survival endpoints is either:
- Overall survival during the course of the study.
- Overall survival rate at 3 and 6 months.
| | |
| Estimated Enrollment: | 9 |
| Actual Study Start Date: | December 21, 2016 |
| Estimated Study Completion Date: | December 1, 2017 |
| Estimated Primary Completion Date: | December 1, 2017 (Final data collection date for primary outcome measure) |
Experimental: 0.35 mg/cm^2 TLD1433 Bladder Dose TLD1433 infusion and photodynamic therapy treatment (PDT): TLD1433 is infused for 1 hour and photodynamic therapy treatment is performed after TLD1433 has been rinsed from the bladder. If treatment with the maximum recommended starting dose of 0.35mg/cm^2 does not raise significant safety concerns as determined by the safety monitoring committee, the therapeutic dose of TLD1433 (0.70mg/cm^2) will be used. | Drug: TLD1433 infusion and photodynamic therapy (PDT) treatment TLD1433 is infused into the bladder, followed by repeated rinsing and treatment of bladder wall with photodynamic therapy (PDT). Other Name: PDT |
| | |
| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Be willing and able to provide written informed consent/assent for the trial.
- Be > 18 years of age on day of signing informed consent.
- Have histologically confirmed NMIBC (T1, Ta, and/or Tis) according to the 2004 WHO classification within 8 weeks prior of treatment initiation. Participants with tumours of mixed transitional / non-transitional cell histology are eligible, but urothelial carcinoma must be the predominant histology. Participants with predominant or exclusively non-urothelial histology are not eligible. Confirmation of histology, grade and stage will be performed by local review and must be completed prior to enrolment.
- For participants with Ta and T1, they must have undergone complete TURBT defined as absence of resectable disease after at least 2 cystoscopy / TURBT procedures. The most recent cystoscopy must have been performed no longer than 8 weeks prior to the first dose of trial treatment.
- Have been considered intolerant or refractory to first-line BCG therapy defined as inability to tolerate or failure to achieve a tumour-free state after at least one induction (minimum of 5 instillations) followed by at either a second induction (minimum of 5 instillations) or at least 2 maintenance instillations. Participants experiencing disease relapse within 12 months or less after finishing the second course of BCG therapy are also considered refractory.
- Are not candidates for cystectomy on medical grounds or refuse radical cystectomy.
- Have a performance status of 70 or more on the Karnofsky Performance Status Scale as assessed within 28 days prior to treatment initiation.
- Have no evidence of upper urothelial carcinoma (involving the upper urinary tract or the urethra) (confirmed by staging to exclude extravesical disease, which may include radiological imaging and/or biopsy) within 3 months of treatment initiation. If previous work up occurred more than 3 months prior to treatment initiation, staging for extravesical disease must be repeated prior to enrolment in order to determine eligibility.
- Have satisfactory bladder function. Ability to retain instillate for a minimum of 1 hour, even with premedication.
- Are available for the duration of the study including follow-up (approximately 12 months).
- Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female participants of childbearing potential must be willing to use 2 methods of birth control (oral contraceptive, pills, diaphragm, or condoms) or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >1 year.
Male participants must agree to use an adequate method of contraception (oral contraceptive, pills, diaphragm, or condoms) starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Exclusion Criteria:
- Past or current muscle invasive (i.e., T2, T3, T4) or metastatic urothelial carcinoma.
- Has concurrent extravesical (i.e. urethra, ureter or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium.
- Have a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. A history of prostate cancer that was treated with definitive intent (surgically or through radiation therapy) is acceptable, provided that the following criteria are met: Stage T2N0M0 or lower; Prostate-Specific Antigen undetectable for 5 years while off androgen deprivation therapy.
- Have a known psychiatric or substance abuse disorder that would interfere with meeting the requirements of the trial.
- Have a history or current evidence of any condition, therapy, surgery or laboratory abnormality that, in the opinion of the investigator, might confound the results of the trial, interfere with the participant's participation in the trial, or is not in the best interest of the participant to participate.
- Currently receiving any photosensitizing medications.
- Have a known hypersensitivity to ruthenium.
- Currently receiving treatment with a prohibited concomitant therapy (refer to 12.2.1, Prohibited Medications).
- Participated in a study with an investigational agent or device within 3 months from the first dose of current study treatment.
- Prior treatment with an intravesical chemotherapeutic agent within 3months of the first dose of current study drug, with the exception of a single perioperative dose of chemotherapy immediately post-TURBT (not considered treatment).
- Have an active infection requiring systemic therapy, including active or intractable urinary tract infection (UTI), in the last month.
- Has any contraindication to general or spinal anesthesia.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
- Known history of Human Immunodeficiency Virus (HIV) (HIV-1/2 antibodies).
- Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Received a live virus vaccine within 30 days of planned start of trial treatment.
- Have a diagnosis of psoriasis.
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: NCT03053635
| | |
| University Health Network |
| Toronto, Ontario, Canada, M5G 2C4 |
| Contact: Michael Nesbitt |
Theralase Inc.
University Health Network, Toronto
Medelis Inc.
WCCT Global
| | | | |
| Principal Investigator: | Girish Kulkarni, MD, PhD | University Health Network, Toronto |
| | |
| Responsible Party: | Theralase Inc. |
| ClinicalTrials.gov Identifier: | NCT03053635 History of Changes |
| Other Study ID Numbers: | TLD1433 Bladder Cancer PDT |
| Study First Received: | February 6, 2017 |
| Last Updated: | February 23, 2017 |
| Individual Participant Data | |
| Plan to Share IPD: | Undecided |
| | |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Theralase Inc.:
| | |
Photodynamic Therapy
Non-muscle invasive bladder cancer (NMIBC)
Urothelial carcinoma | Ta bladder cancer
T1 bladder cancer
Refractory to BCG |
Additional relevant MeSH terms:
| | |
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site | Neoplasms
Urinary Bladder Diseases
Urologic Diseases |
ClinicalTrials.gov processed this record on April 21, 2017