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A Phase 3 Study of UGN-102 for Low Grade Intermediate Risk Non-Muscle-Invasive Bladder Cancer (ATLAS)

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ClinicalTrials.gov Identifier: NCT04688931
Recruitment Status : Recruiting
First Posted : December 30, 2020
Last Update Posted : March 30, 2021
Sponsor:
Information provided by (Responsible Party):
UroGen Pharma Ltd.

Brief Summary:
This is a global, randomized, controlled, open-label Phase 3 study designed to assess the long-term efficacy and safety of UGN-102 (mitomycin) for intravesical solution with or without (±) transurethral resection of bladder tumors (TURBT) versus TURBT alone for the treatment of patients with low grade intermediate risk non-muscle-invasive bladder cancer (LG IR NMIBC).

Condition or disease Intervention/treatment Phase
Bladder Cancer Urothelial Carcinoma Urothelial Carcinoma Bladder Drug: UGN-102 Procedure: TURBT Phase 3

Detailed Description:

Eligible patients will be randomized in a 1:1 ratio to UGN-102 ± TURBT or TURBT alone. Randomization will be stratified by the presence of a previous LG NMIBC episode within 1 year of the current diagnosis (yes or no). Starting at Day 1, patients randomized to the UGN-102 ± TURBT group will receive 6 once-weekly intravesical instillations of UGN-102 and patients randomized to the TURBT alone group will undergo TURBT.

Patients in both treatment groups will return to the clinic at approximately 3 months after the initiation of treatment (7 weeks ± 1 week after the last weekly instillation for the UGN-102 ± TURBT group and 12 weeks ± 1 week after TURBT for the TURBT alone group) to determine response to treatment. Patients determined to have a complete response (CR) will receive no further treatment and will enter the follow-up period of the study. Patients determined to have a non-complete response (NCR) will undergo TURBT of any remaining lesions and will then enter the follow-up period of the study.

During the follow-up period, patients will return to the clinic every 3 months to determine durability of response. Patients will remain on study until completion of all follow-up visits (approximately 24 months after the initiation of treatment) or until recurrence or death is documented, whichever occurs first. Patients determined to have a protocol-defined recurrence at any follow-up or unscheduled visit will be considered to have completed the study and released to the care of their treating physician.

The study is event-driven and patients may be followed beyond 24 months or additional patients may be enrolled to achieve the target number of events required for the study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 632 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Controlled, Open-Label Study of the Efficacy, Durability, and Safety of UGN-102 With or Without TURBT in Patients With Low Grade Intermediate Risk Non-Muscle-Invasive Bladder Cancer (LG IR NMIBC)
Actual Study Start Date : February 19, 2021
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bladder Cancer

Arm Intervention/treatment
Experimental: UGN-102 ± TURBT
6 once-weekly intravesical instillations of 75 mg UGN-102 starting at Day 1 + TURBT for patients who have a NCR at the 3-month disease assessment (7 weeks ± 1 week after the last weekly instillation of UGN-102).
Drug: UGN-102
UGN-102 consists of mitomycin and sterile hydrogel (a proprietary thermally responsive gel) that is used to reconstitute mitomycin before instillation. The reverse thermal properties of UGN-102 allow for local administration of mitomycin as a liquid, with subsequent conversion to a semi-solid gel depot following instillation into the bladder.
Other Name: UGN-102 (mitomycin) for intravesical solution

Procedure: TURBT
The current standard of care for treatment of LG IR NMIBC is TURBT under general anesthesia.
Other Name: Transurethral resection of bladder tumors

Active Comparator: TURBT Alone
TURBT on Day 1 + repeat TURBT for patients who have a NCR at the 3-month disease assessment (12 weeks ± 1 week after the initial TURBT).
Procedure: TURBT
The current standard of care for treatment of LG IR NMIBC is TURBT under general anesthesia.
Other Name: Transurethral resection of bladder tumors




Primary Outcome Measures :
  1. Disease-free survival (DFS) [ Time Frame: Up to 24 months ]
    DFS is defined the same way in both treatment groups, however, it is defined differently for patients who have a CR or NCR at the 3-month disease assessment. For patients who have a CR at 3 months, DFS is defined as the time from randomization to the earliest date of disease recurrence or death due to any cause. Patients who have a NCR at 3 months will be treated with TURBT in both treatment groups and DFS is defined as the time from this TURBT to the earliest date of disease recurrence or death due to any cause.


Secondary Outcome Measures :
  1. Time to recurrence (TTR) [ Time Frame: Up to 24 months ]
    TTR is defined the same way in both treatment groups, however, it is defined differently for patients who have a CR or NCR at the 3-month disease assessment. For patients who have a CR at 3 months, TTR is defined as the time from randomization to the first documented disease recurrence. Patients who have a NCR at 3 months will be treated with TURBT in both treatment groups and TTR is defined as the time from this TURBT to the first documented disease recurrence.

  2. Complete response rate (CRR) [ Time Frame: 3 months ]
    CRR is defined as the percentage of patients who achieve CR at the 3-month disease assessment.

  3. Duration of response (DOR) [ Time Frame: Up to 24 months ]
    DOR is defined as the time from first documented CR to the date of first documented disease recurrence or death due to any cause among patients who achieve CR at the 3-month disease assessment.

  4. Observed CRR at scheduled disease assessment timepoint [ Time Frame: Up to 24 months ]
    Observed CRR at scheduled disease assessment timepoint is defined as the percentage of patients who achieve CR at the 3-month disease assessment and maintain CR up to a particular follow-up disease assessment.

  5. Incidence of TURBT [ Time Frame: Up to 24 months ]
    Incidence of TURBT is defined as the percentage of patients requiring TURBT and the average number of TURBTs per patient in each treatment group.

  6. Changes from baseline in health-related quality of life [ Time Frame: Up to 24 months ]

    The European Organisation for Research and Treatment of Cancer (EORTC) 24-item quality of life questionnaire for patients with NMIBC (QLQ-NMIBC24) is a patient-reported instrument that assesses 11 domains (urinary symptoms, malaise, future worries, bloating and flatulence, intravesical treatment issues, sexual intimacy, risk of contaminating partner, male sexual problems, female sexual problems, sexual function, and sexual enjoyment).

    Descriptive statistics will be used to summarize the scored scales for each of the domains and the change from baseline in the domain scores at each scheduled assessment time point.


  7. Incidence of treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs of special interest, and abnormal clinical laboratory test results (hematology, serum chemistry, and urinalysis). [ Time Frame: Up to 24 months ]
    The percentage of patients with each type of event will be summarized.



Information from the National Library of Medicine

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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. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
  2. Patient who has newly diagnosed or historic LG NMIBC (Ta) histologically confirmed by cold cup biopsy at screening or within 8 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. Negative voiding cytology for high grade (HG) disease within 6 weeks of screening.
  5. Has adequate organ and bone marrow function as determined by the following routine laboratory tests:

    • 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 (ALP) ≤ 2.5 × ULN;
    • Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min.
  6. Has no evidence of active urinary tract infection (UTI).
  7. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for clinical study participants. Women of childbearing potential (defined as premenopausal women who have not been sterilized), including female patients and female partners of male patients, must be willing to use 2 acceptable forms of effective contraception from enrollment through 6 months post-treatment.

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 urothelial carcinoma (UC) within previous 1 year.
  3. History of HG papillary UC in the past 2 years.
  4. Known allergy or sensitivity to mitomycin that in the investigator's opinion cannot be readily managed.
  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 UC.
  9. Current tumor grading of T1.
  10. 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.
  11. History of prior treatment with an intravesical chemotherapeutic agent except for a single dose of chemotherapy immediately post any previous TURBT.
  12. Has previously participated in a study in which they received UGN-102.
  13. Has participated in a study with an investigational agent or device within 30 days of randomization.

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): NCT04688931


Contacts
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Contact: John Saviski 610-247-5164 john.saviski@urogen.com
Contact: Nimrod Gabai 646-793-3606 nimrod.gabai@urogen.com

Locations
Show Show 34 study locations
Sponsors and Collaborators
UroGen Pharma Ltd.
Investigators
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Principal Investigator: Sandip Prasad, MD Atlantic Health System
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Responsible Party: UroGen Pharma Ltd.
ClinicalTrials.gov Identifier: NCT04688931    
Other Study ID Numbers: BL006
First Posted: December 30, 2020    Key Record Dates
Last Update Posted: March 30, 2021
Last Verified: March 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by UroGen Pharma Ltd.:
Non-muscle invasive bladder cancer
Low grade non-muscle invasive bladder cancer
Intermediate risk non-muscle invasive bladder cancer
NMIBC
UGN-102
Mitomycin
Transurethral resection of bladder tumors
TURBT
Additional relevant MeSH terms:
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Carcinoma
Urinary Bladder Neoplasms
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Mitomycins
Mitomycin
Antibiotics, Antineoplastic
Antineoplastic Agents
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors