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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by National Institutes of Health Clinical Center (CC)
Sponsor:
Collaborator:
Rutgers Cancer Institute of New Jersey
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT02015104
First received: December 18, 2013
Last updated: March 14, 2014
Last verified: December 2013
  Purpose

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.

Condition Intervention Phase
Bladder Cancer
Biological: TICE Bacillus Calmette-Guerin (BCG)
Biological: PANVAC
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Improvement in disease-free survival (DFS) with BCG + PANVAC compared with BCG alone. [ Time Frame: 4-5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Estimate the probability distribution of progression-free survival and the time to recurrence. [ Time Frame: 4-5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 54
Study Start Date: December 2013
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 2
Intravesical TICE BCG (50mg) once weekly starting in week 3 for a total of 6 weeks. PANVAC-V 2 x 10(8) pfu SQ at week 0 only. PANVAC-F 1 x 10(9) pfu SQ at weeks 3, 7, 11, and 15
Biological: TICE Bacillus Calmette-Guerin (BCG)
N/A
Biological: PANVAC
A recombinant virus vector vaccine containing genes for human CEA, MUC-1 and three co-stimulatory molecules (designated TRICOM): B7.1, ICAM-1 (intercellular adhesion molecule-1), and LFA-3 (leukocyte function-associated antigen-3).
Experimental: 1
Intravesical TICE BCG (50mg) once weekly starting in week 3 for a total of 6 weeks
Biological: TICE Bacillus Calmette-Guerin (BCG)
N/A

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

3.1.1.1 Patients must have histologically confirmed localized high grade (G3) transitional cell carcinoma (urothelial carcinoma) of the bladder that is stage Ta, T1, and/or CIS confirmed by the Laboratory of Pathology, 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.

3.1.1.2 Patients 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.

3.1.1.3 Patients who are not currently candidates for radical cystectomy (e.g. patient refuses surgery, comorbidities preclude major surgery, etc.).

3.1.1.4 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.

3.1.1.5 ECOG performance status < 2.

3.1.1.6 Patients must have normal organ and marrow function as defined below:

  • absolute neutrophil count > 1,500/mcL
  • platelets > 50,000/mcL
  • total bilirubin < 1.5 X institutional upper limit of normal
  • AST(SGOT)/ALT(SGPT) < 3 X institutional upper limit of normal
  • estimated GFR (calculated using CKD-EPI equation) > 30 mL/min/1.73

sq.m.

3.1.1.7 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 28 days of study entry will suffice.

3.1.1.8 Chest x-ray negative for metastatic disease.

3.1.1.9 Ability of patient to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

3.1.2.1 Previous pelvic radiation for bladder or prostate cancer if performed < 12 months prior to enrollment into the study.

3.1.2.2 Patients who are receiving any other concurrent investigational agents (patients are eligible to enroll 4 weeks after completion of prior agent).

3.1.2.3 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.

3.1.2.4 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.

3.1.2.5 History of allergy or untoward reaction to prior vaccination with vaccinia virus

3.1.2.6 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

3.1.2.7 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.

3.1.2.8 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

3.1.2.9 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 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

3.1.2.10 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.

3.1.2.11 Medical conditions which, in the opinion of the investigators, would jeopardize the patient or the integrity of the data obtained

3.1.2.12 Serious hypersensitivity reaction to egg products

3.1.2.13 Chronic hepatitis infection, including B and C, because of potential immune impairment

3.1.2.14 Clinically significant cardiomyopathy or cardiac complications, including recent myocardial infarction or cerebrovascular accident within one year, and/or unstable or uncontrolled angina

3.1.2.15 Previous intolerance to BCG intravesical therapy suggested by development of systemic BCG infection in the past and/or grade 4 or greater adverse effect by CTCAE v4.0.

3.1.2.16 Patients unable to avoid close contact or household contact with the following high-risk individuals for three weeks after the Day 1 vaccination: (a) children less than or equal to 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczemoid skin disorders, or (d) immunocompromised individuals, such as those with HIV.

3.1.3 Inclusion of Women and Minorities:

Both men and women of all races and ethnic groups are eligible for this trial.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02015104

Contacts
Contact: Sarah Fowler, R.N. (301) 435-6255 fowlers@mail.nih.gov
Contact: Piyush K Agarwal, M.D. (301) 443-8818 agarwalpk2@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
United States, New Jersey
Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States, 08901
Sponsors and Collaborators
Rutgers Cancer Institute of New Jersey
Investigators
Principal Investigator: Piyush K Agarwal, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT02015104     History of Changes
Other Study ID Numbers: 140036, 14-C-0036
Study First Received: December 18, 2013
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Urothelial Cancinoma
Vaccines
Immunotherapy
TICE BCG
Intravesical Treatment

Additional relevant MeSH terms:
Urinary Bladder Diseases
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urologic Diseases
BCG Vaccine
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 19, 2014