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BRIEF TITLE: Study to Evaluate the Safety and Efficacy of INSTILADRIN® (rAd-Interferon (IFN)/Syn3) Administered Intravesically to Patients With High Grade, BCG Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC)

A Phase III, Open Label Study to Evaluate the Safety and Efficacy of INSTILADRIN® (rAd-IFN)/Syn3) Administered Intravesically to Patients With High Grade, BCG Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC)


  • Org Study ID: rAd-IFN-CS-003
  • Secondary ID:
  • NCT ID: NCT02773849
  • NCT Alias:
  • Sponsor: FKD Therapies Oy - Industry
  • Source: FKD Therapies Oy

Description


Learn more about this trial by clicking HERE.

Brief Summary

Previous multi-dose Phase I and Phase II clinical studies have demonstrated that INSTILADRIN (nadofaragene firadenovec) is a safe and effective treatment for BCG-refractory and recurrent NMIBC. This Phase III study is designed to expand those observations using a high dose of INSTILADRIN in patients that are "BCG Unresponsive" which refers to patients with high-grade NMIBC who are unlikely to benefit from and should not receive further intravesical BCG.

Detailed Description


Recombinant IFN alpha2b has pleiotropic effects that contribute to antitumor activity in
Non-Muscle Invasive Bladder Cancer (NMIBC). INSTILADRIN is a non-replicating adenovirus
vector harboring the human IFN alpha2b gene. When combined with the excipient Syn3,
intravesical administration of the rAd-IFN results in transduction of the virus into the
epithelial cell lining in the bladder. The IFN alpha2b gene is incorporated into the cellular
DNA resulting in the synthesis and expression of large amounts of IFN alpha2b protein.
Clinical studies have confirmed that IFN alpha2b protein can be measured in the urine of
patients treated with INSTILADRIN within 24 hours after dosing.

Overal Status Start Date Phase Study Type
Recruiting Start Date: September 2016 Phase 3 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: To evaluate the complete response rate in patients with Carcinoma in situ (CIS), with or without concomitant high-grade Ta or T1 papillary disease.

Primary Outcome 1 - Time Frame: 12 Months

Condition:

  • Superficial Bladder Cancer

Eligibility

Criteria:
Inclusion Criteria:

1. Aged 18 years or older at the time of consent

2. Able to give informed consent

3. Have, at entry, confirmed by a pathology report:

Carcinoma in situ (CIS) only; Ta/T1 high-grade disease with concomitant CIS; or Ta/T1
high-grade disease without concomitant CIS

4. Are BCG Unresponsive" which refers to patients with high-grade NMIBC who are unlikely
to benefit from and who will not receiving further intravesical BCG. The term "BCG
unresponsive" includes patients who did not respond to BCG treatment and have a
persistent high-grade recurrence within 12 months after BCG was initiated, and those
who despite an initial complete response (CR) to BCG, relapse with high-grade CIS
within 12 months of their last intravesical treatment with BCG or relapse with
high-grade Ta/T1 NMIBC within 6 months of their last intravesical treatment with BCG.
The following criteria define the patients who may be included in the study:

- Have received at least 2 previous courses of BCG within a 12 month period -
defined as at least 5 of 6 induction BCG instillations and at least 2 out of 3
instillations of maintenance BCG, or at least two of six instillations of a
second induction course, where maintenance BCG is not given

- Exception: those who have T1 high-grade disease at first evaluation after
induction BCG alone (at least 5 of 6 doses) may qualify in the absence of
disease progression

- At the time of tumor recurrence, patients with CIS alone or high-grade Ta/T1 with
CIS should be within 12 months of last exposure to BCG and patients with Ta/T1
without CIS should be within 6 months of last exposure to BCG

- No maximum limit to the amount of BCG administered

- All visible papillary tumors must be resected and those with persistent T1
disease on transurethral resection of bladder tumor (TURBT) should undergo an
additional re-TURBT within 14 to 60 days prior to beginning study treatment.
Obvious areas of CIS should also be fulgurated.

5. Available for the whole duration of the study

6. Life expectancy >2 years, in the opinion of the investigator

7. Eastern Cooperative Oncology Group (ECOG) status 2 or less

8. Absence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within
the prostatic urethra. Freedom from upper tract disease (if clinically indicated) as
indicated by no evidence of upper tract tumor by either intravenous pyelogram,
retrograde pyelogram, computed tomography (CT) scan with or without urogram, or MRI
with or without urogram performed within 6 months of enrollment

9. Patients with prostate cancer on active surveillance at low risk for progression,
defined as Prostate-Specific Antigen (PSA) < 10 ng/dL, Gleason score 6 and clinical
stage tumor-1 (cT1) are permitted to be in the study at the discretion of the
investigator (see exclusion criterion 10).

10. Female patients of childbearing potential must use maximally effective birth control
during the period of therapy, must be willing to use contraception for 1 month
following the last study drug infusion and must have a negative urine or serum
pregnancy test upon entry into this study. Otherwise, female patients must be
postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile.
'Maximally effective birth control' means that the patient, if sexually active, should
be using a combination of two methods of birth control that are approved and
recognized to be effective by Regulatory Agencies

11. Male patients must be surgically sterile or willing to use a double barrier
contraception method upon enrollment, during the course of the study, and for 1 month
following the last study drug infusion

12. Adequate lab values

Exclusion Criteria:

1. Current or previous evidence of muscle invasive (muscularis propria) or metastatic
disease presented at the screening visit. Examples that increase the risk of
metastatic disease are (but not limited to):

- Presence of lymphovascular invasion and/micropapillary disease as shown in the
histology of the biopsy sample

- Patients with T1 disease accompanied by the presence of hydronephrosis secondary
to the primary tumor

2. Current systemic therapy for bladder cancer

3. Current or prior pelvic external beam radiotherapy within 5 years of entry

4. Prior treatment with adenovirus-based drugs

5. Suspected hypersensitivity to IFN alfa2b

6. Symptomatic urinary tract infection or bacterial cystitis (once satisfactorily
treated, patients can enter the study)

7. Clinically significant and unexplained elevated liver or renal function tests

8. Women who are pregnant or lactating or refuse to commit to use contraception anytime
during the study

9. Any other significant disease or other clinical findings which in the opinion of the
investigator would prevent study entry

10. History of malignancy of other organ system within past 5 years, except treated basal
cell carcinoma or squamous cell carcinoma of the skin and ≤ pathological tumor-2 (pT2)
upper tract urothelial carcinoma at least 24 months after nephroureterectomy. Also
patients with genitourinary cancers other than urothelial cancer or prostate cancer
that are under active surveillance are excluded (see inclusion criterion 9)

11. Patients who cannot hold instillation for 1 hour

12. Patients who cannot tolerate intravesical dosing or intravesical surgical manipulation

13. Intravesical therapy within 8 weeks prior to beginning study treatment with the
exception of:

- cytotoxic agents (e.g. Mitomycin C, doxorubicin and epirubicin) when administered
as a single instillation immediately following a TURBT procedure which is
permitted between 14 to 60 days prior to beginning study treatment

- previous intravesical BCG therapy, which can be given at least 5 weeks before the
diagnostic biopsy required for entry into the study
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Colin P Dinney, MD

Role: Study Chair

Affiliation: M.D. Anderson Cancer Center

Overall Contact

Name: David G Sawutz, PhD

Phone: (416) 697-9515

Email: david.sawutz@fkdtherapies.com

Locations

Facility Status Contact
Banner MD Anderson Cancer Center
Gilbert, Arizona 85234
United States
Recruiting Joseph Mashni, MD
480-256-6444
joseph.mashni@bannerhealth.com
Keck School of Medicine at USC Medical Center
Los Angeles, California 90089
United States
Recruiting Anne Schuckman, MD
323-865-3700
anne.schuckman@med.usc.edu
The Urology Center of Colorado
Denver, Colorado 80211
United States
Recruiting Lawrence I Karsh, MD
303-421-5783
lkarsh@tucc.com
University of Florida - UF Health Davis Center Pavilion and Shands Med Plaza
Gainesville, Florida 32610
United States
Recruiting Paul Crispen, MD

H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida 33612
United States
Recruiting Michael Poch, MD
813-745-1564
Michael.poch@moffitt.org
Emory University School of Medicine
Atlanta, Georgia 30322
United States
Recruiting Mehrdad Alemozaffar, MD
404-778-5864
malemoz@emory.edu
University of Chicago - Section of Urology, MC 6038
Chicago, Illinois 60637
United States
Recruiting Gary Steinberg, MD
773-702-3080
Gsteinbe@surgery.bsd.uchicago.edu
Oshner Clinic Foundation
New Orleans, Louisiana 70121
United States
Recruiting Daniel Canter, MD
504-842-4083
Daniel.canter@ochsner.org
Johns Hopkins Kimmel Cancer Center
Baltimore, Maryland 21287
United States
Recruiting Trinity Bivalacqua, MD
443-287-0385
tbivala1@jhmi.edu
University of Michigan
Ann Arbor, Michigan 48109
United States
Recruiting Jeffrey Montgomery, MD
734-763-9269
montrose@umich.edu
Spectrum Health Medical Group
Grand Rapids, Michigan 49546
United States
Recruiting Brian Lane, MD
616-267-7333
brian.lane@spectrumhealth.org
University of Minnesota
Minneapolis, Minnesota 55455
United States
Recruiting Badrinath Konety, MD
612-625-6401
brkonety@umn.edu
Mayo Clinic - Rochester
Rochester, Minnesota 55905
United States
Recruiting Stephen Boorjian, MD
507-284-4015
Boorjian.Stephen@mayo.edu
Washington University School of Medicine
Saint Louis, Missouri 63110
United States
Recruiting Jerry Adriole, MD
314-362-8200
andrioleg@wustl.edu
Delaware Valley Urology, LLC
Voorhees, New Jersey 08043
United States
Recruiting Gordon Brown, MD
856-673-1613
gbea94@aol.com
Montefiore Medical Center
Bronx, New York 10461
United States
Recruiting Alexander Sankin, MD
267-980-4606
asankin@montefiore.org
SUNY Upstate Medical Center
Syracuse, New York 13210
United States
Recruiting Gennady Bratslavsky, MD
315-464-4473
University of North Carolina (UNC) - Chapel Hill
Chapel Hill, North Carolina 27599-7235
United States
Recruiting Michael Woods, MD
919-966-8217
michael_woods@med.unc.edu
Duke University
Durham, North Carolina 27710
United States
Recruiting Brant Inman, MD
919-681-8760
brant.inman@duke.edu
The University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
United States
Recruiting Michael Cookson, MD
405-271-2410
michael-cookson@ouhsc.edu
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania 17033
United States
Active, not recruiting
The Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania 19104
United States
Recruiting Thomas Guzzo, MD
215-662-2891
thomas.guzzo@uphs.upenn.edu
Thomas Jefferson University
Philadelphia, Pennsylvania 19107
United States
Recruiting Leonard Gomella, MD
215-955-1706
leonard.gomella@jefferson.edu
Regional Urology
Greenville, South Carolina 29605
United States
Recruiting Erik J Busby, MD
864-797-7306
ebusby@ghs.org
Carolina Urologic research Center
Myrtle Beach, South Carolina 29572
United States
Recruiting Neal Shore, MD
843-449-1010
nshore@gsuro.com
Vanderbilt University Medical Center Dept. of Urologic Surgery
Nashville, Tennessee 37232
United States
Recruiting Kirk Keegan, MD
916-202-9121
pat.keegan@vanderbilt.edu
University of Texas Southwestern Medical Center
Dallas, Texas 75390
United States
Recruiting Yair Lotan, MD
214-645-8787
yair.lotan@utsouthwestern.edu
Baylor College of Medicine
Houston, Texas 77030
United States
Recruiting Seth Lerner, MD
713-798-6841
slerner@bcm.edu
MD Anderson Cancer Center
Houston, Texas 77030
United States
Recruiting Ashish Kamat, MD
713-792-3250
akamat@mdanderson.org
The Univ. of Texas Health Science Center at San Antonio
San Antonio, Texas 78229-3900
United States
Recruiting Robert Svatek, MD
210-567-5676
svatek@uthscsa.edu
University of Virginia Health System
Charlottesville, Virginia 22908
United States
Recruiting Tracey Krupski, MD
434-924-0042
tlk6f@virginia.edu
Urology of Virginia
Virginia Beach, Virginia 23462
United States
Recruiting Michael Williams, MD
757-452-3461
mwilliams@urologyofva.net
West Virginia University Cancer Institute
Morgantown, West Virginia 26506
United States
Recruiting Adam Luchey, MD
304-293-2706
adam.luchey@hsc.wvu.edu
University of Wisconsin - Madison
Madison, Wisconsin 53705
United States
Recruiting Tracy Downs, MD
608-263-9534
downs@urology.wisc.edu