Intravesical Photodynamic Therapy (PDT) in BCG Refractory High-Risk Non-muscle Invasive Bladder Cancer (NMIBC) Patients

• Status: Completed
• Trial end date: 2018-08-09
• Target enrollment: 0
• Participant gender: All

Summary

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. Bacillus Calmette-Guerin (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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Theralase Inc.
• Collaborators: Medelis Inc.; University Health Network, Toronto; WCCT Global

Criteria

Inclusion Criteria:

1. Be willing and able to provide written informed consent/assent for the trial.

2. Be > 18 years of age on day of signing informed consent.

3. Have histologically confirmed NMIBC (T1, Ta, and/or Tis) according to the 2004 World Health Organization (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.

4. 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.

5. 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.

6. Are not candidates for cystectomy on medical grounds or refuse radical cystectomy.

7. Have a performance status of 70 or more on the Karnofsky Performance Status Scale as assessed within 28 days prior to treatment initiation.

8. 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.

9. Have satisfactory bladder function. Ability to retain instillate for a minimum of 1 hour, even with premedication.

10. Are available for the duration of the study including follow-up (approximately 12 months).

11. 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.

12. 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:

1. Past or current muscle invasive (i.e., T2, T3, T4) or metastatic urothelial carcinoma.

2. Has concurrent extravesical (i.e. urethra, ureter or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium.

3. 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.

4. Have a known psychiatric or substance abuse disorder that would interfere with meeting the requirements of the trial.

5. 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.

6. Currently receiving any photosensitizing medications.

7. Have a known hypersensitivity to ruthenium.

8. Currently receiving treatment with a prohibited concomitant therapy (refer to 12.2.1, Prohibited Medications).

9. Participated in a study with an investigational agent or device within 3 months from the first dose of current study treatment.

10. 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).

11. Have an active infection requiring systemic therapy, including active or intractable urinary tract infection (UTI), in the last month.

12. Has any contraindication to general or spinal anesthesia.

13. 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.

14. 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.

15. Known history of Human Immunodeficiency Virus (HIV) (HIV-1/2 antibodies).

16. Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., hepatitis C virus (HCV) RNA [qualitative] is detected).

17. Received a live virus vaccine within 30 days of planned start of trial treatment.

18. Have a diagnosis of psoriasis.