Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Urinary Bladder Neoplasms

Carcinoma, Transitional Cell

Non-Muscle Invasive Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

All Drugs and Chemicals

Anti-Infective Agents

Vaccines

Metronidazole

Immunomodulating Agents

BCG Vaccine

Adjuvants, Immunologic

Immunologic Factors

Intravesical TICE BCG (50mg) once weekly starting in week 3 for a total of 6 weeks. PANVAC-V 2 x 10\^8 pfu subcutaneous (SQ) at week 0 only; PANVAC-F 1 x 10\^9 pfu SQ at weeks 3, 7, 11, and 15

Intravesical TICE BCG (50mg) once weekly starting in week 3 for a total of 6 weeks

TICE BCG for intravesical use, is an attenuated, live culture preparation of the Bacillus of Calmette and Guerin (BCG) strain of Mycobacterium bovis

BCG intravesical live (TICE Bacillus Calmette-Guerin (BCG))

A recombinant virus vector vaccine containing genes for human carcinoembryonic antigen (CEA), mucin-1 (MUC-1) and three co-stimulatory molecules (designated Triad of costimulatory molecules (TRICOM): B7.1, intercellular adhesion molecule-1 (ICAM-1), and leukocyte function-associated antigen-3 (LFA-3).

PANVAC

Vladimir Valera Romero, M.D.

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.

Study of Bacillus Calmette-Guerin (BCG) Combined With PANVAC Versus BCG Alone in Adults With High Grade Non-Muscle Invasive Bladder Cancer Who Failed At Least 1 Course of BCG

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

RFS is defined as the time from the start of intravesical Bacillus Calmette-Guerin (TICE BCG) therapy (week 3) until disease recurrence or death due to any cause in each arm. Recurrence is suspected and/or determined by urine cytology and/or cystoscopic exam and then confirmed pathologically after a transurethral resection of bladder tumor (TURBT). Positive cytology in the absence of pathologic confirmation is not considered to be a recurrence.

PFS is the duration of time from start of TICE BCG therapy (week 3) to time of progression or death due to any cause in each study arm, whichever occurs first. Progression is defined as upstaging from a lower stage to a higher stage (e.g., Ta to T1 or T1 to T2-4; or any N+ or M+ in these high grade tumors.).TNM Classification in non-muscle invasive bladder cancer: Ta = Non-invasive papillary carcinoma; T1 = Tumor invades the subepithelial connective tissue; T2-4 = size of primary tumor; N+ or M+ = lymph node involvement and metastasis.

TTR is the duration of time measured from the start of TICE BCG therapy (week 3) until recurrence is noted. Recurrence is suspected and/or determined by urine cytology and/or cystoscopic exam and then confirmed pathologically after a TURBT. Positive cytology in the absence of pathologic confirmation is not considered to be a recurrence.

Serious and non-serious adverse events were assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

OS is defined as the time from treatment start date until date of death or date last known alive.

Rutgers Cancer Institute of New Jersey

National Cancer Institute (NCI)

Principal Investigator

One patient withdrew consent prior to treatment in BCG Alone group.

Intravesical TICE BCG (50mg) once weekly starting in week 3 for a total of 6 weeks. PANVAC-V 2 x 10\^8 pfu subcutaneous (SQ) at week 0 only; PANVAC-F 1 x 10\^9 pfu SQ at weeks 3, 7, 11, and 15

TICE Bacillus Calmette-Guerin (BCG): TICE BCG for intravesical use, is an attenuated, live culture preparation of the Bacillus of Calmette and Guerin (BCG) strain of Mycobacterium bovis

PANVAC: A recombinant virus vector vaccine containing genes for human carcinoembryonic antigen (CEA), mucin-1 (MUC-1) and three co-stimulatory molecules (designated Triad of costimulatory molecules (TRICOM): B7.1, intercellular adhesion molecule-1 (ICAM-1), and leukocyte function-associated antigen-3 (LFA-3).

BCG + PANVAC

Intravesical TICE BCG (50mg) once weekly starting in week 3 for a total of 6 weeks

TICE Bacillus Calmette-Guerin (BCG): TICE BCG for intravesical use, is an attenuated, live culture preparation of the Bacillus of Calmette and Guerin (BCG) strain of Mycobacterium bovis

BCG Alone

Intravesical TICE BCG (50mg) once weekly starting in week 3 for a total of 6 weeks. PANVAC-V 2 x 10\^8 pfu subcutaneous (SQ) at week 0 only; PANVAC-F 1 x 10\^9 pfu SQ at weeks 3, 7, 11, and 15

TICE Bacillus Calmette-Guerin (BCG): TICE BCG for intravesical use, is an attenuated, live culture preparation of the Bacillus of Calmette and Guerin (BCG) strain of Mycobacterium bovis

PANVAC:A recombinant virus vector vaccine containing genes for human carcinoembryonic antigen (CEA), mucin-1 (MUC-1) and three co-stimulatory molecules (designated Triad of costimulatory molecules (TRICOM): B7.1, intercellular adhesion molecule-1 (ICAM-1), and leukocyte function-associated antigen-3 (LFA-3).

Bacillus Calmette-Guerin (BCG) + PANVAC

Bacillus Calmette-Guerin (BCG) Alone

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Ta + CIS

T1 + CIS

Unknown

TNM Classification in non-muscle invasive bladder cancer: Ta - Non-invasive papillary carcinoma; T1 - Tumor invades the subepithelial connective tissue.

CIS - Carcinoma in-situ

Enrollment Disease Status

Number of Patients with≥2 Prior Bacillus Calmette-Guerin (BCG) Induction Before Treatment

Dr. Vladimir Valera Romero

6 months

12 months

One patient withdrew consent after the first dose of drug in the BCG + PANVAC group. One patient withdrew consent prior to treatment in the BCG Alone group.

Percentage of Participants Without Recurrence (Recurrence-free Survival (RFS)) With Bacillus Calmette-Guerin (BCG) + PANVAC Compared With BCG Alone at 6 and 12 Months

Percentage of Participants Without Progression (Progression-Free Survival (PFS)) at 6 and 12 Months

Time to Recurrence

One patient withdrew consent prior to treatment in the BCG Alone group.

Number of Participants With Serious and Non-Serious Adverse Events

Overall Survival (OS)

Overall Study

Antineoplastic Agents

Gemcitabine

Mitomycins

Mitomycin

Antimetabolites

Anti-Bacterial Agents

Antibiotics, Antitubercular

Alkylating Agents

Enzyme Inhibitors

Intravesical sequential treatment of Mitomycin-c 40mg/20ml and Gemcitabine 2000mg/50ml

Intravesical sequential treatment of Mitomycin-c 40mg/20ml and Gemcitabine 2000mg/50ml.

Mitomycin-c 40mg/20ml and Gemcitabine 2000mg/50ml

Ho Kyung Seo, MD

Eui Hyun Jung, Ph.D

Ho Kyung Seo

The aim of this study is to evaluate the effectiveness and safety of mitomycin-c and gemcitabine sequential instillation in BCG unresponsive high risk non-muscle invasive bladder cancer patients.

Phase 2 clinical, multi-institutional, open assignment prospective study

Primary Outcome Measures:

1-year recurrence-free survival period in high-risk groups after sequential injection of Mitomycin-c 40 mg/20 ml and Gemcitabine 2000 mg/50 ml in non-muscle invasive bladder cancer patients in BCG-free high-risk groups.

Secondary Outcome Measures:

Progression Free Survival (PFS), Cystectomy free survival (CFS), Cancer specific survival (CSS), Overall survival (OS) and safety after Mitomycin-c 40mg/20ml and Gemcitabine 2000mg/50ml treatment in non-muscle invasive bladder cancer patients in BCG-free high-risk groups.

The Clinical Effectiveness and Safety of Intravesical Mitomycin-C and Gemcitabine Sequential Therapy

A Study to Assess the Clinical Effectiveness and Safety of Intravesical Mitomycin-C and Gemcitabine Sequential Therapy in Patients With High Risk Non-muscle Invasive Bladder Cancer (NMIBC) Unresponsive to BCG Therapy

Defined as the time when bladder cancer recurrence was first confirmed by biopsy at the initial TURBT date\*, the time of disease progression (see PFS definition), the time of radical bladder resection, the time of bladder cancer metastasis, or the time of bladder cancer death.

defined as the period from the initial TURBT date\* to the time when T stage progresses (e.g., Ta\>T1, CIS\>T1) (PFS1) or muscle invasive bladder cancer (T2 or higher) was first biopsy confirmed (PFS2) or imagingally diagnosed with metastasis to bladder cancer.

Defined as the period from the initial TURBT date\* to the time when radical cystomy was performed.

Duration from initial TURBT date\* to the time of death from bladder cancer

The period from the initial TURBT date\* to the point of death (regardless of cause)

The first safety analysis is conducted on test subjects who have developed toxicity in accordance with CTCAE standards. In particular, urinary disorders such as urinary tract infections and acute urination that occurred after injection of drugs into the bladder are evaluated.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Bacillus Calmette-Guerin (BCG) Combined With PANVAC Versus BCG Alone in Adults With High Grade Non-Muscle Invasive Bladder Cancer Who Failed At Least 1 Course of BCG	NCT02015104	Bladder Cancer	BCG intravesica... PANVAC	18 Years - 100 Years	National Institutes of Health Clinical Center (CC)
Study of Bacillus Calmette-Guerin (BCG) Combined With PANVAC Versus BCG Alone in Adults With High Grade Non-Muscle Invasive Bladder Cancer Who Failed At Least 1 Course of BCG	NCT02015104	Bladder Cancer	BCG intravesica... PANVAC	18 Years - 100 Years	National Institutes of Health Clinical Center (CC)
The Clinical Effectiveness and Safety of Intravesical Mitomycin-C and Gemcitabine Sequential Therapy	NCT06388720	Bladder Cancer	Mitomycin-c 40m...	20 Years -	National Cancer Center, Korea
Study of Bacillus Calmette-Guerin (BCG) Combined With PANVAC Versus BCG Alone in Adults With High Grade Non-Muscle Invasive Bladder Cancer Who Failed At Least 1 Course of BCG	NCT02015104	Bladder Cancer	BCG intravesica... PANVAC	18 Years - 100 Years	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for intravesical treatment