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 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 14003614-C-0036
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Bladder Cancer

Keywords

Urothelial Carcinoma; Vaccines; Immunotherapy; TICE BCG; Intravesical Treatment

Outcome Measures

Primary Outcomes (1)

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

  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.

  Assessed from start of therapy to 6 and 12 months following therapy

Secondary Outcomes (4)

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

  Assessed from start of therapy to 6 and 12 months following therapy

• Time to Recurrence

  Week 3 until recurrence or 12 months (whichever occurred first)

• Number of Participants With Serious and Non-Serious Adverse Events

  Adverse events were assessed from the date treatment consent was signed to the date off study. Approximately 50 months and 12 days for BCG + PANVAC Arm/Group, and 43 months and 12 days for BCG Alone Arm/Group.

• Overall Survival (OS)

  up to 50 months

Study Arms (2)

Bacillus Calmette-Guerin (BCG) + PANVAC

EXPERIMENTAL

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

Biological: BCG intravesical live (TICE Bacillus Calmette-Guerin (BCG)); Biological: PANVAC

Bacillus Calmette-Guerin (BCG) Alone

EXPERIMENTAL

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

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

Interventions

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

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

Bacillus Calmette-Guerin (BCG) + PANVAC; Bacillus Calmette-Guerin (BCG) Alone

PANVAC BIOLOGICAL

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

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed localized high grade (G3) transitional cell carcinoma (urothelial carcinoma) of the bladder that is stage Ta, T1, and/or carcinoma in-situ (CIS) confirmed by the Laboratory of Pathology, National Cancer Institute (NCI) 45 days prior to study entry. This can be obtained at an outside hospital prior to entry into the study or at the NCI. However, all outside pathology specimens will require that the formalin-fixed paraffin embedded tissues be re-read by the Laboratory of Pathology, NCI. For patients enrolled at collaborating trial sites, diagnosis must be confirmed by the Department of Pathology at the institution where the patient is enrolled on the trial.
• Pathology can also be reviewed by the Laboratory of Pathology at the NCI if the participating trial site prefers another pathologic evaluation.
• Patients who are not currently candidates for radical cystectomy (e.g. patient refuses surgery, comorbidities preclude major surgery, etc.).
• Age \>18 years.
• Because no dosing or adverse event data are currently available on the use of BCG in combination with PANVAC in patients \<18 years of age, children are excluded from this study.
• Eastern Cooperative Oncology Group (ECOG) performance status \<2.
• Patients must have normal organ and marrow function as defined below:
• absolute neutrophil count greater than or equal to1,500/mcL
• platelets greater than or equal to 50,000/mcL
• total bilirubin less than or equal to 1.5 X institutional upper limit of normal
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT)(serum glutamic pyruvic transaminase (SGPT) less than or equal to 3 X institutional upper limit of normal
• estimated glomerular filtration rate (GFR) (calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation) greater than or equal to 30 mL/min/1.73 sq.m.
• Computerized Tomography (CT) urogram or Magnetic Resonance Imaging (MRI) urogram. If urogram protocol not available or contrast allergy/poor renal function preclude such imaging, then noncontrast CT or MRI of the abdomen/pelvis within 45 days of study entry will suffice.
• Chest x-ray negative for metastatic disease.
• Ability of patient to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Previous pelvic radiation for bladder or prostate cancer if performed \<12 months prior to enrollment into the study.
• Patients who are receiving any other concurrent investigational agents (patients are eligible to enroll 4 weeks after completion of prior agent).
• Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. There will be at least a 3 week delay from the time of a previous bladder biopsy/transurethral resection of bladder tumor (TURBT) to allow for adequate bladder healing prior to enrollment.
• Patients with a history of encephalitis, multiple sclerosis, or seizures within the last year (from seizure disorder or brain metastasis) should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of allergy or untoward reaction to prior vaccination with vaccinia virus
• Patients should have no evidence of being immunocompromised as listed below:
• Human immunodeficiency virus positivity due to the potential for decreased tolerance and risk for severe side effects
• Active autoimmune diseases requiring treatment or a history of autoimmune disease that might be stimulated by vaccine treatment. This requirement is due to the potential risks of exacerbating autoimmunity. Patients with endocrine disease that is controlled by replacement therapy including thyroid disease and adrenal disease and vitiligo may be enrolled.
• History of splenectomy
• Uncontrolled intercurrent illness which would interfere with the ability of the patient to carry out the treatment program, including, but not limited to, active second malignancy other than a cancer that has been successfully treated resulting in a high likelihood of long-term survival (e.g. completely resected basal cell or squamous cell carcinoma of the skin, stage 1 renal cell carcinoma treated with partial nephrectomy, treated low risk prostate cancer, etc.), inflammatory bowel disease (e.g. Crohn's disease or ulcerative colitis), active diverticulitis, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because the vaccines used in the study may have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the vaccine, breastfeeding should be discontinued if the mother is treated with vaccines. These potential risks may also apply to other agents used in this study. Patients must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while her partner is participating in this study, she should inform her treating physician immediately
• Concurrent use of systemic steroids, except for physiologic doses of systemic steroids for replacement or local (topical, nasal, or inhaled) steroid use. Limited doses of systemic steroids to prevent intravenous (IV) contrast, allergic reaction, or anaphylaxis (in patients who have known contrast allergies) are allowed. Although topical steroids are allowed, steroid eye-drops are contraindicated
• Altered immune function, including immunodeficiency or history of immunodeficiency; eczema; history of eczema, or other eczematoid skin disorders; or those with acute, chronic or exfoliative skin conditions (e.g. atopic dermatitis, burns, impetigo, varicella zoster, severe acne, or other open rashes or wounds). There is an increased risk to patients or contacts with eczema, atopic dermatis, and other immune deficiencies who are at risk for eczema vaccination.
• Medical conditions which, in the opinion of the investigators, would jeopardize the patient or the integrity of the data obtained
• Serious hypersensitivity reaction to egg products

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• Rutgers Cancer Institute of New Jersey: collaborator

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

Location

Related Publications (3)

• Gulley JL, Arlen PM, Tsang KY, Yokokawa J, Palena C, Poole DJ, Remondo C, Cereda V, Jones JL, Pazdur MP, Higgins JP, Hodge JW, Steinberg SM, Kotz H, Dahut WL, Schlom J. Pilot study of vaccination with recombinant CEA-MUC-1-TRICOM poxviral-based vaccines in patients with metastatic carcinoma. Clin Cancer Res. 2008 May 15;14(10):3060-9. doi: 10.1158/1078-0432.CCR-08-0126.

  PMID: 18483372 BACKGROUND

• Kavoussi LR, Torrence RJ, Gillen DP, Hudson MA, Haaff EO, Dresner SM, Ratliff TL, Catalona WJ. Results of 6 weekly intravesical bacillus Calmette-Guerin instillations on the treatment of superficial bladder tumors. J Urol. 1988 May;139(5):935-40. doi: 10.1016/s0022-5347(17)42722-4.

  PMID: 3361667 BACKGROUND

• Crawford ED. Intravesical therapy for superficial cancer: need for more options. J Clin Oncol. 2002 Aug 1;20(15):3185-6. doi: 10.1200/JCO.2002.20.15.3185. No abstract available.

  PMID: 12149286 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Carcinoma, Transitional Cell

Interventions

Panvac-VF

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: Dr. Raju Chelluri
• Organization: National Cancer Institute

raju.chelluri@nih.gov

240-858-3700

Study Officials

• Raju Chelluri, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 18, 2013
• First Posted: December 19, 2013
• Study Start: December 18, 2013
• Primary Completion: September 18, 2018
• Study Completion: May 2, 2019
• Last Updated: July 1, 2025
• Results First Posted: January 22, 2020

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)