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Intravesical Photodynamic Therapy (PDT) in BCG Refractory/Intolerant Non-Muscle Invasive Bladder Cancer (NMIBC) Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03945162
Recruitment Status : Recruiting
First Posted : May 10, 2019
Last Update Posted : November 20, 2019
Sponsor:
Collaborators:
University Health Network, Toronto
Pharma eMarket
Information provided by (Responsible Party):
Theralase Inc.

Brief Summary:
This is a phase II, open-label, single-arm, multi-center Study conducted in Canada, the United States and internationally. Patients with NMIBC CIS with or without resected papillary disease (Ta, T1) that are considered bacillus Calmette-Guerin (BCG)-Unresponsive or who are intolerant to BCG therapy. BCG-Unresponsive is at least one of the following: At least five of six doses of an initial induction course plus at least two of three doses of maintenance therapy; OR, At least five of six doses of an initial induction course plus at least two of six doses of a second induction course. Patients experiencing disease relapse less than 12 months after finishing the second course of BCG therapy are also considered BCG-Unresponsive. The Study will consist of 100 patients who will undergo two (2) PDT treatments employing 0.70 mg/cm^2 of TLD-1433 at Day 0 and Day 180.

Condition or disease Intervention/treatment Phase
Non-Muscle Invasive Bladder Cancer (NMIBC) Refractory to BCG Combination Product: TLD-1433 Bladder infusion and Photodynamic Therapy Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 125 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Clinical Study of Intravesical Photodynamic Therapy in Patients With BCG-Unresponsive Non-Muscle Invasive Bladder Cancer ("NMIBC") Or Patients Who Are Intolerant to BCG Therapy ("Study").
Actual Study Start Date : August 30, 2019
Estimated Primary Completion Date : May 2022
Estimated Study Completion Date : May 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer

Arm Intervention/treatment
Experimental: 0.7 mg/cm^2 TLD-1433 Bladder infusion and Photodynamic Therapy
A single instillation of TLD-1433 (at the therapeutic dose of 0.7 mg/cm^2) will be infused intravesically into the bladder for approximately 60 minutes. Photodynamic therapy treatment is performed after TLD1433 has been rinsed from the bladder. Two treatment procedures will be performed, a primary treatment at Day 0 and a secondary treatment at Day 180 post primary treatment.
Combination Product: TLD-1433 Bladder infusion and Photodynamic Therapy
TLD1433 is infused into the bladder, followed by repeated rinsing and treatment of bladder wall with photodynamic therapy (PDT).
Other Name: PDT




Primary Outcome Measures :
  1. Efficacy, evaluated by the Complete Response (CR) rate. [ Time Frame: Throughout the study and up to the completion of the follow-up phase (12 month) ]

    The primary endpoint of this Study is efficacy, evaluated by the Complete Response ("CR") rate in patients with Carcinoma In-Situ ("CIS") with or without resected papillary disease at 360 days post primary treatment. CR is defined as at least one of the following:

    • Negative cystoscopy and negative (including atypical) urine cytology.
    • Positive cystoscopy with biopsy-proven benign or low-grade NMIBC and negative cytology.
    • Negative cystoscopy with malignant urine cytology, if cancer is found in the upper tract or prostatic urethra and random bladder biopsies are negative.

    For patients who are lost to follow-up or withdraw from the Study before recurrence or death, the CR will be censored at last disease assessment; for patients who start new anti- cancer treatment (i.e.: chemotherapy, immunotherapy or radiotherapy) or undergo a cystectomy, the CR will be censored at the last disease assessment before the start of the new anti-cancer therapy or cystectomy.



Secondary Outcome Measures :
  1. Safety, evaluated by the incidence and severity of Adverse Events. [ Time Frame: Throughout the study and up to the completion of the follow-up phase (12 month) ]
    AE summaries will be provided showing the number and percentage of patients who experienced at least 1 AE. These summaries will be presented by body system and preferred term. AEs resulting in discontinuation will be summarized separately. Adverse Events (AEs) will be monitored from the time of signing the Informed Consent Form (ICF) until End of Study. The relationship of every AEs to the study drug will be determined and documented by the principal investigator whether considered treatment-related, and classified as related, unlikely, possibly, or probably related. All AEs should be treated appropriately. All AEs will be followed until resolution or stabilization or until End of Study (whichever comes first). The severity of each AE will be evaluated as mild, moderate, or severe.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Be willing and able to provide a written Informed Consent Form ("ICF") for the Study.
  2. Be > 18 years of age on day of signing ICF.
  3. Have histologically confirmed NMIBC CIS with or without resected papillary disease (Ta, T1) (high grade) according to the 2004 World Health Organization ("WHO") / International Society of Urologic Pathology classification system up to 8 weeks prior to the treatment procedure.

    • Confirmation of histology, grade and stage will be performed by local review and must be completed prior to enrolment.

  4. Patients with Ta, or T1 disease, must have undergone complete Trans-Urethral Resection of the Bladder Tumour ("TURBT") defined as the absence of resectable disease after at least 1 cystoscopy or TURBT procedure.

    • The most recent cystoscopy must have been performed no longer than 8 weeks prior to the treatment procedure.

  5. Considered BCG-Unresponsive, which is at least one of the following:

    • At least five of six doses of an initial induction course, plus at least two of three doses of maintenance therapy
    • At least five of six doses of an initial induction course, plus at least two of six doses of a second induction course
    • Patients experiencing disease relapse less than 12 months after finishing the second course of BCG therapy are also considered BCG-Unresponsive.
  6. Are not candidates for cystectomy on medical grounds or refuse radical cystectomy.
  7. Have an Eastern Cooperative Oncology Group ("ECOG") performance score of 0 to 1.
  8. Have satisfactory bladder function. Ability to retain Study Drug for a minimum of 1 hour.
  9. Are available for the duration of the Study including follow-up (approximately 12 months).
  10. Female patients of childbearing potential must have a negative Human Chorionic Gonadotropin ("HCG") pregnancy test taken during the screening visit and confirmed prior to the treatment procedure.
  11. Female patients of childbearing potential must be willing to use 2 methods of birth control (i.e.: oral contraceptive, pills, diaphragm or condoms) or be surgically sterile, or abstain from heterosexual activity for two weeks after the treatment procedure. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for >1 year.
  12. Intolerance of BCG therapy

Exclusion Criteria:

  1. Past or current muscle invasive (i.e.: T2, T3, T4) or metastatic urothelial carcinoma.
  2. Has concurrent extravesical (i.e.: urethra, ureter, renal pelvis, prostate or prostatic ducts) non-muscle invasive transitional cell carcinoma of the urothelium. (confirmed by staging to exclude extravesical disease, which may include radiological imaging and/or biopsy) within 3 months of enrollment:

    If previous work up occurred more than 3 months prior to enrollment, staging for extravesical disease must be repeated prior to enrolment in order to determine eligibility.

  3. Active gross hematuria.
  4. 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, in situ cervical cancer or localized prostate cancer under active surveillance with Gleason 6 disease. 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 (PSA) undetectable for 2 years while off androgen deprivation therapy or no more than 2 consecutive rising PSAs.
  5. Have a history or current evidence of any condition, therapy, surgery or laboratory abnormality that, in the opinion of the PI, might confound the results of the Study, interfere with the patient's participation in the Study, or is not in the best interest of the patient to participate.
  6. Currently receiving treatment with a prohibited concomitant therapy (refer to 12.2.1, Prohibited Medications).
  7. Participated in a study with an investigational agent or device within 1 month from the first dose of current Study treatment.
  8. Prior treatment with an intravesical chemotherapeutic agent within 1 month of the first dose of current Study Drug, with the exception of a single perioperative dose of chemotherapy immediately post-TURBT (not considered treatment).
  9. Have an active infection requiring systemic therapy, including active or intractable Urinary Tract Infection ("UTI"), not resolved prior to the procedure.
  10. Has any contraindication to general or spinal anesthesia.
  11. Is pregnant or breastfeeding within the projected duration of the Study, starting with the screening visit through to two weeks following the second TLD-1433 instillation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03945162


Contacts
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Contact: Shawn Shirazi, Ph.D 416-699-5273 ext 229 sshirazi@theralase.com
Contact: Arkady Mandel, MD, Ph.D. 416-699-5273 ext 242 amandel@theralase.com

Locations
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Canada, Ontario
London Health Sciences Centre Recruiting
London, Ontario, Canada
Contact: Wendy Shoff         
Principal Investigator: Joseph Chin, MD         
University Health Network Recruiting
Toronto, Ontario, Canada, M5G 2C4
Contact: Michael Nesbitt         
Principal Investigator: Girish Kulkarni, MD         
Canada, Quebec
McGill University Health Centre Recruiting
Montréal, Quebec, Canada
Contact: Raphael Freitas         
Principal Investigator: Wassim Kassouf, MD         
Sponsors and Collaborators
Theralase Inc.
University Health Network, Toronto
Pharma eMarket
Investigators
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Principal Investigator: Girish Kulkarni, MD, FRCSC University Health Network, Toronto

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Responsible Party: Theralase Inc.
ClinicalTrials.gov Identifier: NCT03945162    
Other Study ID Numbers: TLD-1433 Bladder Cancer PDT
First Posted: May 10, 2019    Key Record Dates
Last Update Posted: November 20, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
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Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases