Bladder Cancer Clinical Trial
Official title:
A Randomized, Prospective, Phase II Study to Determine the Efficacy of Bacillus Calmette-Guerin (BCG) Given in Combination With PANVAC[TM] Versus BCG Given Alone in Adults With High Grade Non-Muscle Invasive Bladder Cancer (NMIBC) Who Failed at Least 1 Induction Course of BCG
Background:
- Many cancers produce two particular proteins. The immune system can target these to attack
the cancer. The PANVAC vaccine puts genes for these proteins inside a virus vaccine so the
body sees the proteins as foreign invaders and attacks them. Researchers will test PANVAC on
people with high grade non-muscle invasive bladder cancer. They will give it to people who
have not responded to the usual treatment, bacillus Calmette-Guerin (BCG) over several weeks.
They want to see if PANVAC plus BCG is better than BCG alone.
Objective:
- To compare the effects of PANVAC plus BCG therapy, to BCG therapy alone.
Eligibility:
- Adults 18 and older with high grade non-muscle invasive bladder cancer who failed at least
1 course of BCG.
Design:
- Participants will be screened with blood and urine tests and abdominal scans.
- Participants will be randomly assigned to get BCG only or BCG plus PANVAC.
- They will have up to 10 visits over 15 weeks. Most of these are part of usual cancer
care.
- They will have blood and urine tests.
- All participants will get BCG in 6 weekly injections.
- One group will also get PANVAC in 5 injections over 15 weeks.
- Between weeks 17 and 20, participants will undergo tests of the tumor area as part of
their usual care. They will have cystoscopy, exam under anesthesia, and bladder biopsy.
Results will be used to evaluate the different treatments.
- Participants will have quarterly follow-up visits for up to 2 years.
Background:
- High grade (G3) non-muscle invasive urothelial carcinoma of the bladder (stages Ta, T1,
and carcinoma in situ (CIS) has a high rate of recurrence and progression
- The standard of care therapeutic agent is a single induction course of bacillus
Calmette- Guerin (BCG)
- Although a second induction course can be used in patients who fail a single induction
course of BCG, only 35% of patients who failed an initial induction course will
experience 12 month disease-free survival after receiving a second induction course
- For those patients failing a second induction course, radical cystectomy with pelvic
lymphadenectomy is the recommended treatment, although it has a high morbidity rate and
a small but real mortality rate
- Therefore, there is an unmet need for localized treatment for patients who fail an
initial induction course of BCG that can potentially improve upon the poor results of a
second induction course of BCG
- Recently, a unique pox viral vector-based vaccine, PANVAC, has been shown to induce a
cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8)
antigen-specific immune response against the tumor-associated antigens (TAAs),
carcinoembryonic antigen (CEA) and mucin-1 (MUC-1). This vaccine also contains
transgenes for three human T cell co-stimulatory molecules that can potentially augment
an immune response
- We hypothesize that the combined administration of BCG and PANVAC may augment the
BCG-induced cytotoxic T lymphocyte response against bladder cancer cells expressing
MUC-1 and/or CEA and potentially reverse BCG failure in patients that have failed one
induction course of BCG
Objectives:
-To determine if there is an improvement in disease-free survival (DFS) with BCG + PANVAC
compared with BCG alone in a phase II study in non-muscle invasive high-grade urothelial
carcinoma of the bladder who have failed to respond to intravesical BCG within 1 year post
treatment.
Eligibility:
- Individuals who have failed at least one previous induction course of intravesical BCG,
defined as histologically confirmed persistent or relapsing tumor present on post-BCG
endoscopic evaluation. All BCG failures will be considered for inclusion into the study,
including BCG-refractory,-resistant, and -relapsing, as defined in the Rationale and
Background. For the purposes of the study, BCG-refractory and BCG-resistant subjects
will be considered to have BCG-persistent disease.
- Patients who are not currently candidates for radical cystectomy (e.g. patient refuses
surgery, comorbidities preclude major surgery, etc.).
- Normal organ function, Eastern Cooperative Oncology Group (ECOG) 0-2.
Design:
- This is a randomized, open label prospective, Phase II study in subjects with non-muscle
invasive high grade urothelial carcinoma of the bladder who have failed at least one
induction course of intravesical BCG, randomized to one of the following arms: BCG
intravesical live (TICE BCG) +PANVAC or TICE BCG alone. Randomization is stratified by
BCG treatment subgroup.
- All subjects will receive intravesical TICE BCG (50mg) as per usual standard of care
once weekly starting in week 3 for a total of 6 weeks.
- The combination arm will receive the pox viral vaccines that contain the transgenes for
CEA and MUC-1 (both with modified human leukocyte antigen serotype within HLA-A A
serotype group (HLA-A2) agonist epitopes) as well as 3 human T-cell costimulatory
molecules, B7-1, intercellular adhesion molecule (ICAM-1), and lymphocyte function
associated antigen 3 (LFA-3) [rV-PANVAC (vaccinia) and rFPANVAC (fowlpox)] as follows:
- rV-PANVAC 2 x 10(8) pfu subcutaneous (SQ) at week 0 only.
- rF-PANVAC1 x 10(9) pfu SQ at weeks 3, 7, 11, and 15.
- For this Phase II study, we will test the hypothesis that subjects in the TICE BCG
+PANVAC arm have better disease-free survival than subjects in the TICE BCG alone arm.
- Patient accrual is targeted at one patient per month during the first 6 months and 1-2
patients per 1-2 months afterwards, and follow-up period after completing accrual will
be 12 months post treatment.
- Based on a power of 84% and type 1 error (1-sided) of 0.15, a total of 49 subjects will
need to be accrued.
- Allowing for a proportion of the subjects not being evaluable, a maximum of 54 subjects
will be accrued.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Not yet recruiting |
NCT06034015 -
A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of APL-1501 Extended Release (ER) Capsules Compared to APL-1202 Immediate Release (IR) Tablets in Healthy Volunteers
|
Phase 1 | |
Recruiting |
NCT04235764 -
En-bloc Transurethral Resection of Bladder Tumor (En-bloc TURBT) Specimens Using a Redesigned Surgical Resectoscope Device
|
||
Completed |
NCT02371447 -
VPM1002BC in Recurrent Non-muscle Invasive Bladder Cancer
|
Phase 1/Phase 2 | |
Recruiting |
NCT04081246 -
Transurethral Modified En Bloc Resection For Large Bladder Tumours.
|
N/A | |
Recruiting |
NCT06059547 -
Neoadjuvant Immunotherapy in Combination With the Anti-GDF-15 Antibody Visugromab (CTL-002) for Treatment of Muscle Invasive Bladder Cancer
|
Phase 2 | |
Terminated |
NCT04779489 -
Checkpoint Inhibitor and Radiation Therapy in Bulky, Node-Positive Bladder Cancer
|
N/A | |
Not yet recruiting |
NCT04493489 -
Propranolol Adjuvant Treatment of Bladder Cancer
|
Phase 2 | |
Completed |
NCT03520231 -
Study Comparing Denosumab With Standard Treatment in Urothelial Cancer Patients With Bone Metastases
|
Phase 2 | |
Recruiting |
NCT04537221 -
Nordic Cystectomy Study III - Transfusion
|
||
Withdrawn |
NCT03007771 -
Magnetic Resonance-guided High-Intensity Focused Ultrasound (MR-HIFU) Used for Mild Hyperthermia
|
Phase 1 | |
Completed |
NCT01955408 -
Severity of Overactive Bladder Symptoms in Patients After Synergo Treatment
|
N/A | |
Completed |
NCT04487457 -
Prospective Study to Evaluate the Blood Kinetics of Immune Cells and Immunosuppressive Cytokines After Exposure to an Immunity Checkpoint Inhibitor (ICI): Study of the Impact of Chemotherapy
|
||
Active, not recruiting |
NCT04383210 -
Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Advanced Solid Tumors
|
Phase 2 | |
Recruiting |
NCT05562791 -
A Study of 68Gallium PSMA-PET/CT Scans in People With Bladder Cancer
|
Phase 1 | |
Completed |
NCT00199849 -
NY-ESO-1 Plasmid DNA (pPJV7611) Cancer Vaccine
|
Phase 1 | |
Completed |
NCT02781428 -
To Detect the Sensitivity of the UroMark Assay
|
||
Recruiting |
NCT04738630 -
Study of HX008 for the Treatment of BCG-Unresponsive Non-muscle Invasive Bladder Cancer
|
Phase 2 | |
Completed |
NCT03980041 -
Study to Evaluate the Efficacy/Safety of IPI-549 in Combination With Nivolumab in Patients With Advanced Urothelial Carcinoma (MARIO-275)
|
Phase 2 | |
Active, not recruiting |
NCT03978624 -
Window of Opportunity Study of Pembrolizumab Alone and in Combinations in Bladder Cancer
|
Phase 2 | |
Completed |
NCT04534309 -
Behavioral Weight Loss Program for Cancer Survivors in Maryland
|
N/A |