Brief Title
A Phase 2b Study of UGN-102 for Low Grade Intermediate Risk Non-Muscle-Invasive Bladder Cancer
Official Title
A Phase 2b, Single-Arm, Multicenter Trial to Evaluate the Efficacy and Safety of UGN-102 as Primary Chemoablative Therapy in Patients With Low Grade (LG) Non-Muscle-Invasive Bladder Cancer (NMIBC) at Intermediate Risk of Recurrence
Brief Summary
The study is investigating the efficacy and safety of UroGen's UGN-102 to treat patients with
Low Grade (LG) Non Muscle Invasive Bladder Cancer (NMIBC) at intermediate risk of recurrence.
Detailed Description
This study is a prospective, open-label, single-arm, multicenter Phase 2b trial designed to
assess the efficacy and safety of UGN-102 treatment instilled in patients diagnosed with LG
NMIBC, including newly diagnosed patients, and determined to have intermediate risk of
progression, defined as 1 or 2 of the following: multiple tumors, solitary tumor >3 cm, or
recurrence (≥ 1 occurrence of LG NMIBC within 1 year of the current diagnosis). Eligible
patients will be treated with 6 weekly instillations of UGN-102.
UGN-102 is a reverse thermal hydrogel formulated with MMC. The product is specifically
formulated to achieve a liquid state at 4°C and to transition to a water-soluble gel at body
temperature. The advantage of delivering Mitomycin to the urinary bladder using UGN-102
relies on preclinical and clinical literature documenting that concentration and dwell time
correlate directly with the therapeutic efficacy of MMC when used to treat Urothelial
Carcinoma (UC)
The ablative effect of UGN-102 will be evaluated at the Primary Disease Evaluation (3 MONTH)
assessment, which will take place 5 weeks ±1 week after the last weekly instillation (3
months after initiation of study medication). Response will be determined based on visual
evaluation by cystoscopy (appearance, number, size, and location of the lesions) and, if
there are remaining lesions, by histopathology of the remaining lesions. CR is defined as
having no detectable disease (NDD) and will be assessed visually during cystoscopy and also
upon urine cytology. In the event that the investigator is not sure, and there is suspect
tissue, a small biopsy will be taken from the suspect tissue to confirm CR in addition to
cystoscopy and urine cytology. Patients who achieve a CR will continue to have monthly
telephone contacts to document any adverse events and changes in concomitant medications and
will be assessed at 6, 9, and 12 months after the first instillation of UGN-102 for evidence
of disease recurrence. The group of patients considered nonresponders (non-CR) will
discontinue the study and continue with standard of care according to their treating
physician.
Safety will be determined based on physical examination, laboratory assessments, and a review
of AEs. All safety data will be reviewed on an ongoing basis, including close review and
follow up of any unexpected AE related to UGN-102 and qualified per National Cancer Institute
(NCI) Common Terminology Criteria for Adverse Events (CTCAE) as Grade 3 or 4.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Complete response (CR) rate for UGN-102 treatment
Secondary Outcome
Durable complete response (DCR) rate
Condition
Bladder Cancer
Intervention
UGN-102
Study Arms / Comparison Groups
UGN-102
Description: 75 mg Mitomycin C (MMC) in 56 mL admixture (1.33 mg MMC per 1 mL of admixture).
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
63
Start Date
October 15, 2018
Completion Date
October 21, 2020
Primary Completion Date
January 3, 2020
Eligibility Criteria
Inclusion Criteria:
1. Willing and able to sign an informed consent and comply with the protocol.
2. Has newly diagnosed or historic LG NMIBC (Ta) histologically confirmed by cold cup
biopsy at screening or within 6 weeks of screening.
3. Is at intermediate risk for progression, defined as having 1 or 2 of the following:
- Presence of multiple tumors;
- Solitary tumor > 3 cm;
- Recurrence (≥ 1 occurrence of LG NMIBC within 1 year of the current diagnosis).
4. Has negative voiding cytology for HG disease at or within 6 weeks of enrollment.
5. Willing to use 2 acceptable forms of effective contraception from enrollment through 6
months post treatment if the participant is female or the female partner of a male
participant and is of childbearing potential (defined as premenopausal women who have
not been sterilized).
6. Has adequate organ and bone marrow function as determined by routine laboratory tests
as below:
- Leukocytes ≥ 3,000 cells per μL;
- Absolute neutrophil count ≥ 1,500 cells per μL;
- Platelets ≥ 100,000 per μL;
- Hemoglobin ≥ 9.0 g/dL;
- Total bilirubin ≤ 1.5 x upper limit of normal (ULN);
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN;
- Alkaline phosphatase ≤ 2.5 × ULN;
- Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min.
7. Has no evidence of active urinary tract infection (UTI) at Screening and Baseline
visits.
- In the case of symptomatic UTI, the patient will be treated with a full course of
antibiotics, and study medication will be postponed until resolution. In the case
of asymptomatic bacteriuria, the use of prophylactic antibiotics and postponement
of study medication is left to the discretion of the Principal Investigator (PI).
Exclusion Criteria:
1. History of carcinoma in situ (CIS) on preliminary cystoscopy within 5 years of
enrollment.
2. Received Bacillus Calmette-Guérin (BCG) treatment for UC within previous 2 years.
3. History of HG papillary UC in the past 2 years.
4. Known allergy or sensitivity to mitomycin.
5. Clinically significant urethral stricture that would preclude passage of a urethral
catheter.
6. History of pelvic radiotherapy.
7. History of:
- Neurogenic bladder;
- Active urinary retention;
- Any other condition that would prohibit normal voiding.
8. Past or current muscle invasive (ie, T2, T3, T4) or metastatic UC or concurrent upper
tract urothelial carcinoma (UTUC).
9. Has participated in a study with an investigational agent or device within 30 days of
enrollment.
10. History of prior treatment with an intravesical chemotherapeutic agent with the
exception of a single dose of chemotherapy immediately after any previous TURBT.
11. Has an underlying substance abuse or psychiatric disorder such that, in the opinion of
the investigator, the patient would be unable to comply with the protocol.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
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Location Countries
Israel
Location Countries
Israel
Administrative Informations
NCT ID
NCT03558503
Organization ID
TC-BC-12
Responsible Party
Sponsor
Study Sponsor
UroGen Pharma Ltd.
Study Sponsor
, ,
Verification Date
December 2020