Carcinoma in Situ, Non-muscle Invasive Bladder Cancer, Transitional Cell Carcinoma
Conditions
Keywords
Urinary Bladder Neoplasms, Neoplasms, Urologic Neoplasms, Urogenital Neoplasms, Neoplasms by Site, Urinary Bladder Diseases, Urologic Diseases, TURBT, Valstar
Brief summary
This is a Phase 3b open-label, randomized, parallel-arm, multicenter study to evaluate the efficacy and safety of 10 monthly intravesical administrations of maintenance therapy with valrubicin following induction with valrubicin as compared to induction with valrubicin only in subjects with CIS of the bladder. The randomization will be 1:1 and subjects will be stratified by tumor type (CIS plus papillary disease vs. CIS only) and time from last bacillus Calmette-Guerin (BCG) failure (\>1 year vs. \<1 year).
Interventions
DRUGVALSTAR - Maintenance Therapy
Treatment phase - 10 monthly intravesical installations starting 10 to 12 weeks after the beginning of induction. Follow-up phase
OTHERNo Maintenance treatment ( Standard of Care)
Subjects randomized to No Maintenance (Standard of Care) will not receive any additional intravesical therapy
Sponsors
Endo Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Is 18 years of age and older at time of consent signing 2. Have histologically confirmed diagnosis of CIS of the bladder and received valrubicin induction therapy per the labeled indication. 3. Is disease-free following induction with intravesical valrubicin * Disease-free is defined as negative biopsy 10 to 12 weeks after the initiation of valrubicin induction * Valrubicin induction is defined as having received at least 3 of 6 weekly instillations 4. Is available for the duration of the study including follow-up (minimum 12 months from randomization) 5. Have an Eastern Cooperative Oncology Group (ECOG) performance status grade of 2 or less 6. Have no evidence of urothelial carcinoma involving the upper urinary tract or prostatic urethra (confirmed by extravesical work up, which may include radiological imaging and/or biopsy) within 6 months prior to randomization 7. Subjects (male and female) of child-bearing potential (including female subjects who are post-menopausal for less than 1 year) must be willing to practice abstinence or effective contraception (as defined by the investigator) during the study and be willing and able to continue contraception for 30 days after their last dose of study treatment 8. Is able to understand and give written informed consent
Exclusion criteria
1. Have current or previous history of muscle-invasive bladder cancer (MIBC) 2. Current or previous history of lymph node positive and/or metastatic bladder cancer 3. Have current evidence of pure squamous cell carcinoma, pure adenocarcinoma or pure undifferentiated carcinoma of the bladder 4. Is currently receiving systemic anti-cancer therapy (cytotoxic/cytostatic, immunotherapy or radiation) 5. Received treatment with an investigational agent within 30 days or 5 half-lives prior to randomization, whichever is longer 6. Received treatment with an intravesical chemotherapeutic agent (other than valrubicin or a single administration of mitomycin C post-transurethral resection of bladder tumor \[TURBT\]) within 3 months prior to randomization 7. Received treatment with valrubicin other than induction within 3 months prior to randomization 8. Have contraindication to valrubicin * Known hypersensitivity to anthracyclines or polyoxyl castor oil * Small bladder capacity, i.e. unable to tolerate a 75 mL instillation * Concurrent urinary tract infection 9. Absolute neutrophil count (ANC) \<1000/µL and hemoglobin \<10 g/dL 10. Have active cardiovascular disease such as myocardial infarction within the past 3 months, unstable angina pectoris, congestive heart failure (NYHA Class III or IV) or uncontrolled cardiac arrhythmia 11. Female subjects who are pregnant or lactating 12. Subjects of childbearing potential who are unwilling to practice abstinence or effective contraception (as defined by investigator) during the study and for 30 days after last dose of study treatment 13. Have current or history of documented or suspected malignancy of any organ system (diagnosed, treated or untreated) within the past 5 years (with the exception of adequately treated basal cell or squamous cell carcinoma of the skin and asymptomatic non-metastatic prostate cancer either previously successfully treated or currently under active surveillance or receiving hormone therapy only) 14. Is unable to tolerate intravesical administration or intravesical surgical manipulation (cystoscopy or biopsy) even with premedication 15. Have ongoing clinically significant active infections 16. Have any medical or psychiatric condition which, in the opinion of the investigator, would preclude the participant from adhering to the protocol or completing the trial per protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate the Efficacy of Maintenance Therapy With Valrubicin After Induction With Valrubicin, as Compared to Induction With Valrubicin Only in Subjects With CIS of the Bladder. | 2 years | time interval from randomization to an event. An event is defined as tumor recurrence (any stage or grade), tumor progression to muscle-invasive bladder cancer (MIBC), metastatic bladder cancer or death from any cause, whichever occurs first. Tumor recurrence or progression must be documented by biopsy/transurethral resection of bladder tumor (TURBT). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate the Safety and Tolerability of Maintenance Therapy With Valrubicin After Induction With Valrubicin, as Compared to Induction With Valrubicin Only in Subjects With CIS of the Bladder | 2 years | The occurrence of serious adverse events (SAEs), occurrence of local adverse reactions (LARs), results of vital signs, physical exams and laboratory test, and study discontinuation due to inability to complete valrubicin instillations |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Maintenance Therapy Chemotherapeutic: EN3329-301 (VALSTAR)
VALSTAR - Maintenance Therapy: Treatment phase - 10 monthly intravesical installations starting 10 to 12 weeks after the beginning of induction. Follow-up phase | 1 |
| No Maintenance (Standard of Care) Subjects randomized to No Maintenance (Standard of Care) will not receive any additional intravesical therapy
No Maintenance treatment ( Standard of Care): Subjects randomized to No Maintenance (Standard of Care) will not receive any additional intravesical therapy | 0 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Subject terminated by Sponsor | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Maintenance Therapy |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 0 / 0 |
| serious Total, serious adverse events | 0 / 1 | 0 / 0 |
Outcome results
Primary
To Evaluate the Efficacy of Maintenance Therapy With Valrubicin After Induction With Valrubicin, as Compared to Induction With Valrubicin Only in Subjects With CIS of the Bladder.
time interval from randomization to an event. An event is defined as tumor recurrence (any stage or grade), tumor progression to muscle-invasive bladder cancer (MIBC), metastatic bladder cancer or death from any cause, whichever occurs first. Tumor recurrence or progression must be documented by biopsy/transurethral resection of bladder tumor (TURBT).
Time frame: 2 years
Population: No analysis completed due to limited enrollment (1 subject) prior to study termination.
Secondary
To Evaluate the Safety and Tolerability of Maintenance Therapy With Valrubicin After Induction With Valrubicin, as Compared to Induction With Valrubicin Only in Subjects With CIS of the Bladder
The occurrence of serious adverse events (SAEs), occurrence of local adverse reactions (LARs), results of vital signs, physical exams and laboratory test, and study discontinuation due to inability to complete valrubicin instillations
Time frame: 2 years
Population: No analysis completed due to limited enrollment (1 subject) prior to study termination.