Phase 1
N=12
Durvalumab and Vicineum in Subjects With High-Grade Non-Muscle-Invasive Bladder Cancer Previously Treated With Bacillus Calmette-Guerin (BCG)
Urinary Bladder Neoplasms
Bottom Line
View on ClinicalTrials.gov: NCT03258593 ↗Enrolled (actual)
12
Serious AEs
26.7%
Results posted
Oct 2023
Primary outcome: Primary: Number of Grades 1-5 Adverse Events — 12; 3; 15; 9 adverse events
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Durvalumab (Drug); Vicineum (Drug); Acetaminophen (Drug); Antihistamine (Drug); Bladder Biopsy (Procedure); TURBT (Procedure); Cystoscopy (Procedure); Urine cytology (Diagnostic_test); Electrocardiogram (Diagnostic_test); CT (Diagnostic_test); MRI (Diagnostic_test)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Aug 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Grades 1-5 Adverse Events |
12; 3; 15; 9; 3; 12 | — |
| SECONDARY Urinary Epithelial Cell Adhesion Molecule (EpCAM) Compared Between Participants Who Have a Clinical Response to Therapy vs. Those Who do Not Respond |
— | — |
| SECONDARY Response Rate |
41.6; 66.6; 46.6; 58.3; 33.3; 53.3 | — |
| SECONDARY Pharmacokinetic Parameters in Urine Maximum Concentration (Cmax) of Vicineum |
2.5; 1.5; 3.2; 4320.0; 305.4; 3738.7 | — |
| SECONDARY Change in Programmed Death-ligand 1 (PD-L1) Levels Between Responders and Non-Responders |
573.4; 342.5; 533.8; 505.9; 228.4; 489.7 | 0.202 |
| SECONDARY Change in Programmed Cell Death Protein 1 (PD-1) Levels Between Responders and Non-Responders |
— | — |
| SECONDARY Change in Programmed Death-ligand 1 (PD-L1) Levels Between Participants Who Respond and Have Stable Disease (SD), and Those With Progressive Disease (PD) |
533.8; 342.5; 505.9; 516; 228.4; 494.8 | 0.863 |
| SECONDARY Change in Programmed Cell Death Protein 1(PD-1) Levels Between Participants Who Respond and Have Stable Disease (SD), and Those With Progressive Disease (PD) |
— | — |
| SECONDARY Changes in the Immune Parameters Obtained From Blood Samples |
4.340; 0.640; 3.850; 3.290; 1.750; 3.120 | <0.001 sig |
| SECONDARY Changes in the Immune Parameters Obtained From Biopsies |
— | — |
| SECONDARY Disease Free Survival (DFS) |
12.8; 50.1; 13.2 | — |
Summary
Background:
Non-muscle-invasive bladder cancer is in the early stages. But it usually comes back after treatment. The drugs Vicineum and Durvalumab may help the immune system find and destroy cancer cells.
Objective:
To test if the drugs Durvalumab and Vicineum together are safe and effective to treat people with bladder cancer that has not spread to the muscle in the bladder.
Eligibility:
People ages 18 and older who have bladder cancer that has not spread to the muscle in the bladder and was treated unsuccessfully with Bacillus Calmette-Guerin
Design:
Participants will be screened with:
Medical history
Physical exam
Blood and urine tests
Tumor sample from previous surgery. If one is not available, they will have a biopsy: A small piece of tumor is removed.
Cystoscopy to examine the inside of the bladder. This may include a biopsy or removing tumors.
Computed tomography (CT) or magnetic resonance imaging (MRI): They lie in a machine that takes pictures of the body.
Electrocardiogram to test heart function
Participants will receive Durvalumab and Vicineum in 2 phases:
First phase: Durvalumab every 4 weeks and Vicineum once a week for 3 months
Second phase: Durvalumab every 4 weeks and Vicineum once every other week
Participants will have tumor samples taken every 3 months. They will have blood and urine tests throughout the study.
Participants will continue treatment for up to 2 years.
Participants will have a visit about 30 days after their last treatment. This includes blood and urine tests. It may include a cytoscopy or additional biopsies.
Eligibility Criteria
- INCLUSION CRITERIA:
- Patients must have histologically or cytologically confirmed by National Cancer Institute (NCI) Laboratory of Pathology as high-grade non-muscle invasive urothelial (transitional cell carcinoma) of the bladder as follows:
- Carcinoma-in-situ (CIS) with or without papillary tumors
- High-grade Ta or T1 disease based on a biopsy/transurethral resection of bladder tumor (TURBT) performed within 12 weeks of the initial dose of study treatment. If multiple bladder biopsies/TURBTs are required to confirm eligibility, the timing of the last bladder biopsy to the initial dose of study treatment must be within 12 weeks.
- Patients with persistent T1 high grade disease on TURBT following a single induction course of BCG (Bacillus Calmette-Guerin) (at least 5 of 6 doses) may also be eligible for this trial provided that the patient is surgically unfit for cystectomy as deemed by the investigator or the patient declines cystectomy.
- Subjects with BCG unresponsive disease as defined by the Society of Urologic Oncology and the Food and Drug Administration (FDA): Subjects must have received at least two courses of intravesical BCG (at least 5 of 6 induction doses of BCG and at least 2 of 3 maintenance doses of BCG under a maintenance regimen or at least 2 doses of a repeat induction course). Please note exception above for persistent T1 disease. There is no upper limit on the amount of prior BCG a subject may have received.
- Patients who have met eligibility criterion above must have received last BCG dose within a year of enrollment.
- The investigator must document that he/she believes the subject would not benefit from additional BCG treatment at the time of study entry.
- Age >= 18 years at time of signing the informed consent form (ICF). Because no dosing or adverse event data are currently available on the use of Vicineum in combination with durvalumab in patients = 9.0 g/dL
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (> 1500 per mm^3)
- Platelet count >= 75 x 10^9/L (>75,000 per mm^3)
- Serum bilirubin less than or equal to 1.5 x institutional upper limit of normal (ULN).
- Aspartate aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT) serum glutamate-pyruvate transaminase (SGPT) less than or equal to 2.5 x institutional ULN
- Creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
- Males: Creatinine CL (mL/min) = (Weight (kg) x (140 - Age))/72 x serum creatinine (mg/dL)
- Females: Creatinine CL (mL/min) = (Weight (kg) x (140 - Age) x 0.85)/72 x serum creatinine (mg/dL)
- Female subjects must either be of non-reproductive potential (i.e., post-menopausal as described below) OR history of surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
- Women = 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, or had chemotherapy-induced menopause with last menses >1 year ago
- The effects of Vicineum and durvalumab on the developing human fetus are unknown. For this reason, all sexually active subjects agree to use barrier contraception (i.e., condoms) while receiving study treatment and for 120 days following their last dose of study treatment. Female subjects of child-bearing potential and male subjects whose sexual partners are women of childbearing potential (WOCBP) agree to use barrier contraception and a second form of contraception while receiving study treatment and for 4 months following their last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediatel
Data sourced from ClinicalTrials.gov (NCT03258593). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.