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BRIEF TITLE: Study to Evaluate the Efficacy and Tolerability of Intravesical Vicinium™ in Subjects With Non Muscle-Invasive Carcinoma in Situ and/or High-Grade Papillary Disease of the Bladder Treated With BCG

Open-Label, Multicenter, Ph 3 Study to Evaluate the Efficacy and Tolerability of Intravesical Vicinium™ in Subjects With Non Muscle-Invasive Carcinoma in Situ and/or High-Grade Papillary Disease of the Bladder Treated With BCG


  • Org Study ID: VB4-845-02-IIIA
  • Secondary ID:
  • NCT ID: NCT02449239
  • NCT Alias:
  • Sponsor: Viventia Bio - Industry
  • Source: Viventia Bio

Brief Summary

Because of the high risk for development of muscle invasive disease, cystectomy is recommended for CIS, high-grade Ta and T1 patients who experience disease recurrence following intravesical therapy. Vicinium is an experimental agent that may provide an alternative to cystectomy

Detailed Description


Bladder cancer is the 6th most common cancer in the United States, affecting more men than
women. The usual first treatment for NMIBC (Ta, T1, and CIS) is transurethral resection of
the bladder tumors followed by intravesical immunotherapy, most commonly with bacillus
Calmette-Guérin (BCG).

Because of the high risk for development of muscle invasive disease, cystectomy is
recommended for CIS and high-grade Ta and T1 patients who experience disease recurrence
following intravesical therapy. For patients unable or unwilling to undergo cystectomy,
treatment options are limited.

Vicinium contains the active pharmaceutical ingredient VB4-845, which is a recombinant fusion
protein produced in Escherichia coli (E. coli) that expresses a humanized single-chain
antibody fragment specific for the epithelial cell adhesion molecule (EpCAM) antigen linked
to ETA(252-608). Once bound to the EpCAM antigen on the surface of carcinoma cells, Vicinium
is internalized through an endocytic pathway. The ETA(252-608) is cleaved off and induces
cell death by irreversibly blocking protein synthesis.

In vitro and in vivo pharmacology demonstrated that Vicinium exhibits potent activity
[inhibitory concentration 50% (IC50) = 0.001 - 10 pM] against numerous cell lines and
effectively inhibits tumor growth in several human xenograft animal models. A Phase 2 study
evaluated once-weekly instillations of Vicinium 30 mg over 6 or 12 weeks, followed by up to 3
maintenance cycles (3 once-weekly instillations followed by a 9-week drug-free period) in 45
subjects with histologically-confirmed TCC of the bladder and residual CIS with or without
concurrent Ta or T1 who were refractory or intolerant to BCG. A complete response (defined as
no histological evidence of disease and negative urine cytology at the 3-monthly evaluations)
was achieved by 44% of subjects, and 16% of subjects remained disease-free at 1-year. A
post-study assessment found that these subjects were still disease-free at 18-25 months. The
median time to recurrence was 134 days longer in subjects who received 12 weeks of induction
therapy compared to 6 weeks.

This is an open-label, non-randomized, multicenter study in adults with NMIBC, specifically
CIS (with or without papillary disease), high-grade Ta or any grade T1 papillary disease, who
have previously failed BCG treatment (i.e., not those who are intolerant) with or without
interferon. The study consists of a Screening period, a 12-week Induction Phase, and a
Maintenance Phase of up to 21 monthly cycles for a total treatment period of up to 104 weeks.
This is an outpatient study, but all treatments are administered in the study clinic.

Overal Status Start Date Phase Study Type
Recruiting Start Date: August 2015 Phase 3 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Complete response rate

Primary Outcome 1 - Time Frame: Up to 24 months

Condition:

  • Bladder Cancer

Eligibility

Criteria:
Inclusion Criteria:

1. Histologically-confirmed non muscle-invasive urothelial carcinoma (transitional cell
carcinoma) of the bladder as follows:

1. CIS (with or without papillary disease) OR

2. Any grade T1 papillary disease OR

3. High-grade Ta papillary disease based on a biopsy within 8 weeks of the initial
dose of study treatment. If multiple bladder biopsies are required to confirm
eligibility, the last bladder biopsy to the initial dose of study treatment must
be within 8 weeks. This diagnosis must be confirmed by the independent central
pathology reviewer prior to subject enrollment. A subject with persistent T1
disease on the second (i.e., restaging) TURBT may be enrolled in this study only
if the investigator documents the subject declines cystectomy.

2. Subjects must have received adequate BCG treatment defined as at least 2 courses of
BCG, i.e., at least one induction and one maintenance course or at least 2 induction
courses. The initial induction course must be at least 5 treatments within a 7-week
period. The second course (induction or maintenance) must be at least 2 treatments
within a 6-week period. The 5+2" doses of BCG must be given within approximately 1
year (i.e., the start of one course to start of the second course within 12 months ±1
month) and for the same disease episode for which the subject is enrolling. Treatment
must be considered "full-dose" BCG (see Section 10). If additional doses or courses of
BCG above the minimum "5+2" are given, these do not have to be within the same
approximate 12 month timeframe.

Subjects who were unable to receive at least 5 doses of BCG in a first course and at
least 2 doses of BCG in a second course due to intolerance are not eligible.

Subjects who began their initial course of BCG with "full-dose" BCG and required
dose-reductions due to adverse events but are still able to tolerate at least "5+2"
doses of BCG are considered to meet the requirement for "adequate BCG." Subjects who
received less than "full dose" BCG (e.g., 1/3rd dosing) as a standard regimen and not
due to dose reductions because of AEs are not eligible.

The BCG may have been given in combination with interferon. When BCG is given
simultaneously in combination with interferon, 1/3rd dosing of BCG is acceptable.

3. The subject's disease is refractory or has relapsed following adequate BCG treatment.
Refractory disease is defined as disease which persists at the first evaluation
following adequate BCG. Relapsed disease is defined as having a complete response to
adequate BCG but recurs at a subsequent evaluation.

Subjects will enroll into one of three cohorts based on their type of disease and the
time to refractory/relapsed disease following their last dose of BCG as follows:

- Cohort 1: Subjects with CIS with or without associated papillary disease whose
disease is determined to be refractory or relapsed within 6 months of the last
dose of adequate BCG treatment.

- Cohort 2: Subjects with CIS with or without associated papillary disease whose
disease is determined to be refractory or relapsed more than 6 months but within
11 months of the last dose of adequate BCG treatment.

- Cohort 3: Subjects with high-grade Ta or any grade T1 papillary disease (without
CIS) whose disease is determined to be refractory or relapsed within 6 months of
the last dose of adequate BCG treatment.

For eligibility and cohort assignment, 6 months is defined as 30 weeks i.e., 26 weeks
(6 months) plus an additional 4 weeks to accommodate scheduling variations and for
diagnostic work-up and 11 months is defined as 50 weeks i.e., 48 weeks (11 months)
plus an additional 2 weeks to accommodate scheduling variations and for diagnostic
work-up.

For subjects enrolling in Cohort 2: The investigator documents he/she would not treat
the subject with additional BCG at the time of study entry.

4. Male or non-pregnant, non-breastfeeding female, age 18 years or older at date of
consent.

5. All women of childbearing potential (WOCBP) must have a negative pregnancy test within
7 days of the first dose of study therapy. A woman is not of childbearing potential if
she has undergone surgical sterilization (bilateral tubal ligation, total
hysterectomy, or bilateral oophorectomy) or if she is ≥55 years of age and has had no
menstrual bleeding of any kind including menstrual period, irregular bleeding,
spotting, etc., for at least 12 months and there is no other cause of amenorrhea
(e.g., hormonal therapy, prior chemotherapy).

6. 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. WOCBP and males whose sexual partners are WOCBP agree to use barrier
contraception and a second form of contraception while receiving study treatment and
for 120 days following their last dose of study treatment.

7. Karnofsky performance status ≥ 60 (Appendix 1).

8. Adequate organ function, as defined by the following criteria:

- Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x
upper limit of normal (ULN);

- Total serum bilirubin ≤ 1.5 x ULN (CTCAE Grade ≤ 1);

- Serum creatinine ≤ 1.5 x ULN; or a creatinine clearance ≥40 mL/min;

- Hemoglobin ≥8.0 g/dL;

- Absolute neutrophil count ≥1500/mm3;

- Platelets ≥75,000/mm3

9. Ability to understand and sign an Independent Ethics Committee- or Institutional
Review Board-approved informed consent document indicating that the subject (or
legally acceptable representative) has been informed of all aspects of the trial and
is willing and able to comply with scheduled visits, treatment plan, laboratory tests,
and other study procedures. The informed consent document must be signed prior to the
subject undergoing tests or procedures solely for determining study eligibility and
prior to receiving any protocol treatment.

Exclusion Criteria:

1. The subject is pregnant or breastfeeding.

2. Evidence of urethral or upper tract transitional cell carcinoma (TCC) within the past
2 years. Subjects with T1 disease must have no evidence of upper or lower tract
disease or a more advanced stage of disease by CT urogram or MRI urogram of the
abdomen and pelvis performed within 8 weeks of the first dose of study treatment. If
intravenous contrast is contraindicated, retrograde ureteropyelography, or CT or MRI
without intravenous contrast may be performed.

3. Subjects with hydronephrosis, except for those subjects where hydronephrosis has been
longstanding (i.e., predates the diagnosis of the CIS, Ta or T1 by more than 2 years)
and diagnostic evaluation at Screening shows no evidence of tumor. Subjects with
hydronephrosis that is unequivocally unrelated to upper tract malignancy may be
considered eligible with Sponsor approval.

4. Any intravesicular or other chemotherapy treatment within 2 weeks or any
investigational agent within 4 weeks prior to the initial dose of study drug.

5. History of recurrent severe urinary tract infections (UTIs) per investigator judgment.
Subjects with a current UTI requiring antibiotic treatment may defer the initiation of
Vicinium treatment on Day 1 until resolution of the UTI (even if this extends the
screening period requirements to start of Vicinium treatment).

6. Active, uncontrolled impairment of the urogenital, renal, hepatobiliary,
cardiovascular, gastrointestinal, neurologic or hematopoietic systems which, in the
opinion of the Investigator, would predispose the subject to the development of
complications from the administration of intravesical therapy and/or general
anesthesia.

7. The subject has a diagnosis of another malignancy within 2 years before the first dose
of study treatment, except for superficial skin cancer or localized solid tumors
deemed cured by surgery and not treated with systemic anticancer therapy and not
expected to require anticancer therapy in the next 2 years i.e., while the subject may
be taking study treatment. However, subjects with low-risk prostate cancer, e.g.:

- Clinically localized disease (≤T2a) and

- Gleason score 6 (3+3) and

- Serum PSA <10 ng/mL undergoing active surveillance may be enrolled with agreement
of the sponsor.

8. A QTc interval of >470 msec by the Fridericia formula (QTcF), at the Screening ECG. If
the subject's QTcF is >470 msec on the initial ECG, a total of 3 ECGs should be
obtained at least 3 minutes apart and all within 30 minutes. The average of the 3
QTcF's will be used to determine eligibility. Known or suspected causes of prolonged
QTc can be treated (e.g., hypocalcemia, hypokalemia, hypomagnesimia) and the ECGs may
be repeated. If the subject initiates treatment with a drug known to prolong the QTc
during the Screening period after the initial Screening ECGs were obtained, the
Screening ECGs must be repeated once the new drug has reached steady state to ensure
the average QTcF remains ≤470 msec. For subject's whose heart rate is <60 bpm, the
Bazett correction formula (QTcB) may be used.

9. Subjects who, in the opinion of the Investigator, cannot tolerate intravesical
administration or intravesical surgical manipulation (cystoscopy, biopsy) due to the
presence of serious comorbid condition(s) (e.g., uncontrolled cardiac or respiratory
disorders).

10. Local or severe allergy to any components of the drug regimen.
Show More

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Contact

Name: Erminia Cafasso

Phone: 973-366-1901

Email: erminia.cafasso@elevenbio.com

Locations

Facility Status Contact

Birmingham, Alabama 35294
United States
Recruiting Ralee Bunt
205-934-2272
erikabunt@uabmc.edu

Phoenix, Arizona 85032
United States
Recruiting Debbi Mobley
602-493-6626
debbi@bcgoncology.com

Tucson, Arizona 85741
United States
Recruiting Lisa Alvarez
520-795-5830
LisaA@uasapc.com

Little Rock, Arkansas 72211
United States
Recruiting Katie O'Brien
501-219-8900
katie@arkansasurology.com

Los Angeles, California 90017
United States
Recruiting Gabriela Luevano
562-693-4477
gluevano@airesearch.us

Los Angeles, California 90048
United States
Recruiting Shiblee Nomanee
310-854-9898
nomanees@towerurology.com

Los Angeles, California 90089
United States
Recruiting Ileana Aldana
323-865-0702
ileana.aldana@med.usc.edu

Los Angeles, California 90095
United States
Recruiting Nazy Zomorodian
310-794-2858
nzomorodian@mednet.ucla.edu

Redwood City, California 94062
United States
Recruiting Linda McFeeters
650-362-8250
linda@sequoiauc.com

San Bernardino, California 92404
United States
Recruiting Charity Hernandez
909-881-0555
charity@sburology.com

Sherman Oaks, California 91411
United States
Recruiting Stacey Gomez
818-990-5020
stacey.gomez@skyuro.com

Torrance, California 90505
United States
Recruiting Stacey Gomez
310-602-5018
stacey.gomez@skyuro.com

Englewood, Colorado 80113
United States
Recruiting Landen Neeper
303-733-8848
l.neeper@uradenver.com

Washington, District of Columbia 20010
United States
Recruiting Lambros Stamatakis, MD
202-877-7011
lambros.stamatakis@medstar.net

Bradenton, Florida 34205
United States
Recruiting Pallavi Purohit
941-792-0340
ppurohit@uswfllp.com

Daytona Beach, Florida 32114
United States
Recruiting Jonelle Horsely
386-239-8500
Jonelle.Horsley@auihealth.com

Orlando, Florida 32803
United States
Recruiting Felipe Valerio
407-992-3170
felipe.valerio@flhosp.org

Saint Petersburg, Florida 33710
United States
Recruiting Pallavi Purohit
727-381-8667
ppurohit@uswflip.com

Tampa, Florida 33612
United States
Recruiting Lori Hoenemeyer
813-972-2000
Lori.Hoenemeyer@va.gov

Wellington, Florida 33449
United States
Recruiting Carmen Franqui
561-753-3175
cfranqui@palmbeachurology.com

Atlanta, Georgia 30322
United States
Recruiting Almira Catic
404-778-7397
almira.catic@emory.edu

Honolulu, Hawaii 96813
United States
Active, not recruiting

Coeur d'Alene, Idaho 83814
United States
Recruiting Patti Patterson
208-667-0621
ppatterson@niurology.com

Meridian, Idaho 83642
United States
Recruiting Misty Pichardo
208-639-4946
mpichardo@idurology.com

Chicago, Illinois 60612
United States
Withdrawn

Lake Barrington, Illinois 60010
United States
Recruiting Betty Anderson
847-382-5080
banderson@compurocare.com

Melrose Park, Illinois 60160
United States
Withdrawn

Jeffersonville, Indiana 47130
United States
Recruiting Christina Nessel
812-206-8164
cnessel@1sturology.com

Fairway, Kansas 66205
United States
Recruiting Ashley Shores
913-588-1897
ashores@kumc.edu

Lenexa, Kansas 66214
United States
Active, not recruiting

Wichita, Kansas 67208
United States
Recruiting Dorothy Roush
316-689-9542
dorothy.roush@viachristi.org

New Orleans, Louisiana 70112
United States
Recruiting Sree Harsha Mandava
504-988-1205
smandava@tulane.edu

Glen Burnie, Maryland 21061
United States
Recruiting Wendy Paxton
410-760-9400
wpaxton@cua.md

Boston, Massachusetts 02111
United States
Recruiting Elizabeth Grimm
617-636-8501
egrimm@tuftsmedicalcenter.org

Burlington, Massachusetts 01805
United States
Recruiting Doreen Browne
781-744-3158
Doreen.L.Browne@Lahey.org

Worcester, Massachusetts 01655
United States
Recruiting Jonathan Guerard
508-856-1956
jonathan.guerard@umassmemorial.org

Ann Arbor, Michigan 48109
United States
Recruiting Steven Perry
734-615-7228
perryste@med.umich.edu

Lebanon, New Hampshire 03756
United States
Recruiting Alyssa McGuire
603-650-6054
alyssa.j.mcguire@hitchcock.org

Brick, New Jersey 08724
United States
Recruiting Lynn Schwieters
732-840-4300
lschwieters@coastalurologynj.net

Lawrenceville, New Jersey 08648
United States
Recruiting Melissa Ciatteo
609-895-0735
mciatteo@advancedmed.info

Morristown, New Jersey 07960
United States
Recruiting Darlene Wendling
201-274-9825
darlene.wendling@atlantichealth.org

Albuquerque, New Mexico 87109
United States
Recruiting Jeremy Kilburn
505-872-4091
jkilburn@accumetrx.com

Albany, New York 12208
United States
Recruiting Brenda Romeo
518-262-8579
amcurologyresearch@mail.amc.edu

Bronx, New York 10461
United States
Recruiting JoAnn Horn
347-842-1715
johor@montefiore.org

New York, New York 10032
United States
Recruiting Bridget Buckley-Matura
212-304-5543
Bb2771@cumc.columbia.edu

Poughkeepsie, New York 12601
United States
Recruiting Lisa Gray
845-437-5002
lgray@premiermedicalhv.com

Syracuse, New York 13210
United States
Recruiting Diane Gould
315-464-6105
gouldd@upstate.edu

Concord, North Carolina 28025
United States
Active, not recruiting

Middleburg Heights, Ohio 44130
United States
Recruiting Amie Demming
440-340-9010
ademming@crssites.com

Oklahoma City, Oklahoma 73014
United States
Recruiting Riza Fabreo
410-271-8777
Riza-Fabreo@ouhsc.edu

Portland, Oregon 97239
United States
Recruiting Wesley Stoller
503-220-8262
stoller@ohsu.edu

Bala-Cynwyd, Pennsylvania 19004
United States
Recruiting Cheryl Zinar
610-667-0458
czinar@ucsepa.com

Bryn Mawr, Pennsylvania 19010
United States
Recruiting Caryn Bucko
610-525-2515
cbucko@uhsurology.com

Pittsburgh, Pennsylvania 15232
United States
Recruiting Dawn McBride
412-605-3015
mcbridedl@upmc.edu

Charleston, South Carolina 29401
United States
Recruiting Susan Caulder
843-789-7816
susan.caulder@va.gov

Charleston, South Carolina 29425
United States
Recruiting Jessica Jenkins
843-876-0630
jenkijn@musc.edu

Myrtle Beach, South Carolina 29572
United States
Withdrawn

Knoxville, Tennessee 37909
United States
Withdrawn

Dallas, Texas 75231
United States
Recruiting Maritza Cardoso
214-580-1482
cardoso@urologyclinics.com

El Paso, Texas 79920
United States
Recruiting Melinda Metzger-Abamukong
915-742-3432
MAbamukong@genevausa.org

Houston, Texas 68130
United States
Recruiting Rezwana Zahir
713-351-0630
rezwana.zahir@hmutx.com

Houston, Texas 77030
United States
Recruiting Sharon Harrison
713-798-4001
sharons@bcm.edu

Temple, Texas 76508
United States
Recruiting Tina Amlin
254-724-5710
tina.amlin@bsw.health.org

Charlottesville, Virginia 22908
United States
Recruiting Elaine Woodson
434-982-3704
mew3u@viginia.edu

Richmond, Virginia 23235
United States
Recruiting Noah Vann
804-288-2785
ncvann@uro.com

Halifax, Nova Scotia B3H 2Y9
Canada
Recruiting Noreen Millar
902 473 6604
Noreen.Millar@nshealth.ca

Barrie, Ontario L4M 7G1
Canada
Active, not recruiting

Kingston, Ontario K7L 3J7
Canada
Withdrawn

London, Ontario N6A 5W9
Canada
Withdrawn

Oakville, Ontario L6H 3P1
Canada
Recruiting Rupi Dhaliwal
905-338-3130
rdhaliwal@malehealth.com

Toronto, Ontario M4N 3M5
Canada
Recruiting Marlene Kebadbdjian
416-480-6100
Marlene.kebabdjian@sunnybrook.ca

Toronto, Ontario M5G 2C4
Canada
Recruiting Kathy Li
416 946 4501
Kathy.li@uhn.ca

Toronto, Ontario
Canada
Withdrawn

Montreal, Quebec H2X 0A4
Canada
Recruiting Helen Leonard
514-890-8000
helene.leonard.chum@ssss.gouv.qc.ca

Montreal, Quebec H4A 3J1
Canada
Recruiting Marie Claude Joncas
514-934-1934
Marie-claude.joncas@muhc.mcgill.ca

Pointe-Claire, Quebec H9R 4S3
Canada
Recruiting Karen Anderson

karen@ultramed.ca

Sherbrooke, Quebec J1E 3Z6
Canada
Recruiting Elsie Morneau
819-829-3281
Emorneau.chus@ssss.gouv.qc.ca