Intravesical Administration of rAd-IFN/Syn3 in Patients With BCG-Refractory or Relapsed Bladder Cancer

NCT01687244 | Completed Phase 2 Results DMC

• 1 other identifier: rAd-IFN-CS-002
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

This Phase 2 study is designed to assess the efficacy and safety of INSTILADRIN (rAd-IFN with Syn3) when given intravesically to patients with high grade non-muscle invasive bladder cancer who are refractory to or have relapsed from BCG therapy. The pharmacodynamics of INSTILADRIN will also be studied by measuring the interferon (IFNα2b) levels excreted in the urine. rAd-IFN is a non-replicating recombinant adenovirus type 5 (Ad5)-vector encoding the interferon alpha-2b (IFNα2b) gene. Syn 3 is clinical surfactant excipient which enhances the ability of the adenoviral vector to transfect cells in the bladder wall.

Conditions

Superficial Bladder Cancer

Keywords

BCG Refractory or Relapsed Superficial Bladder Cancer; rAd-IFN; Syn3; Intravesical; transitional cell carcinoma of the bladder; superficial non-muscle invasive tumor; Interferon alpha2b; INSTILADRIN

Outcome Measures

Primary Outcomes (1)

• Incidence of High Grade-Recurrence Free Survival at 360 Days

  Following the initial treatment, patients were clinically evaluated and re-treated at the Days 90, 180, and 270 time points, as outlined below. The decision to repeat treatment was determined by the clinical response observed following the previous treatment(s). Patients were assessed for High-Grade disease recurrence by cytology, cystoscopy and, if clinically indicated, biopsies were performed to obtain accurate staging. If no evidence of recurrence of High-Grade disease was detected, then a further dose of rAd-IFN/Syn3 was administered as maintenance therapy. Patients who had recurrence of High-Grade disease were withdrawn from treatment but were followed for survival and time to cystectomy. At 360 Days, a final efficacy evaluation was performed for patients receiving 4 doses of drug. This included cystoscopy, cytology, and biopsy.

  360 Days

Secondary Outcomes (12)

• Safety of rAd-IFN/Syn3

  360 Days

• Incidence of High Grade Recurrence-Free Survival at 3 Months (90 Days).

  90 Days

• Incidence of High Grade-Recurrence-Free Survival at 6 Months (180 Days).

  180 Days

• Incidence of High Grade-Recurrence-Free Survival at 9 Months (270 Days).

  270 Days

• Incidence of Cystectomy in All Patients

  360 Days

Study Arms (2)

rAd-IFN Dose 1x10^11vps/ml

EXPERIMENTAL

Subjects will be randomly assigned to one of two INSTILADRIN arms.

Drug: INSTILADRIN

rAd-IFN dose 3x10^11 vps/ml

EXPERIMENTAL

Subjects will be randomly assigned to one of two INSTILADRIN arms.

Drug: INSTILADRIN

Interventions

INSTILADRIN DRUG

The INSTILADRIN components will be mixed with a diluent. The total dose will be given as a single, one-hour intravesical administration which may, depending on clinical response, be repeated every 3 months up to a maximum of 4 instillations.

Also known as: rAd-IFN/Syn3

rAd-IFN Dose 1x10^11vps/ml; rAd-IFN dose 3x10^11 vps/ml

Eligibility Criteria

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

You may qualify if:

• Aged 18 years or older at the time of consent
• Able to give informed consent
• Subjects with high grade BCG-refractory or relapsed NMIBC including
• High grade non-invasive papillary carcinomas (Ta) and subjects with high grade tumors that invade sub-epithelial connective tissue (T1) or
• Carcinoma in situ (CIS) only or
• CIS and Ta or T1 tumors Refractory is defined as failure to achieve a disease-free state at six months after adequate induction of BCG therapy with either maintenance or re-induction at 3 months. Adequate induction is defined as a minimum of 5 out of 6 induction doses and adequate maintenance is defined as a minimum of 2 out of 3 doses of treatment.
• Relapse is defined as recurrence within 1 year after a complete response to BCG treatment
• Complete resection of visible papillary lesions or CIS by TURBT or endoscopic resection between 14 and 60 days prior to beginning study treatment
• Available for the whole duration of the study
• Life expectancy \>2 years, in the opinion of the investigator
• ECOG status 2 or less
• Absence of upper tract urothelial carcinoma
• Female subjects 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 subjects must be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile.
• Male subjects 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.
• Adequate laboratory values.

You may not qualify if:

• Current or previous evidence of muscle invasive or metastatic disease
• Current systemic therapy for bladder cancer
• Current or prior pelvic external beam radiotherapy
• Prior treatment with adenovirus-based drugs
• Suspected hypersensitivity to interferon alpha
• Existing urinary tract infection or bacterial cystitis
• Clinically significant and unexplained elevated liver or renal function tests
• Women who are pregnant or lactating
• Severe cardiovascular disease
• History of malignancy of other organ system within past 5 years (except treated basal cell carcinoma or squamous cell carcinoma of the skin)
• Subjects who cannot hold instillation for 1 hour
• Subjects who cannot tolerate intravesical dosing or intravesical surgical manipulation
• Intravesical therapy within 6 weeks of enrollment

Sponsors & Collaborators

• FKD Therapies Oy: lead

Related Publications (2)

• Konety BR, Lotan Y, Myers A. Safety of nadofaragene firadenovec-vncg: review of data from phase 2 and phase 3 studies. Can J Urol. 2025 Mar 18;32(1):29-36. doi: 10.32604/cju.2025.064710.

  PMID: 40194933 DERIVED

• Shore ND, Boorjian SA, Canter DJ, Ogan K, Karsh LI, Downs TM, Gomella LG, Kamat AM, Lotan Y, Svatek RS, Bivalacqua TJ, Grubb RL 3rd, Krupski TL, Lerner SP, Woods ME, Inman BA, Milowsky MI, Boyd A, Treasure FP, Gregory G, Sawutz DG, Yla-Herttuala S, Parker NR, Dinney CPN. Intravesical rAd-IFNalpha/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study. J Clin Oncol. 2017 Oct 20;35(30):3410-3416. doi: 10.1200/JCO.2017.72.3064. Epub 2017 Aug 23.

  PMID: 28834453 DERIVED

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: David Sawutz, PhD
• Organization: FKD Therapies Oy

david.sawutz@fkdtherapies.com

416-607-9515

Study Officials

• Colin Dinney, MD

  M.D. Anderson Cancer Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The participant did not know if they received a high or low dose.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2012
• First Posted: September 18, 2012
• Study Start: September 1, 2012
• Primary Completion: October 1, 2015
• Study Completion: January 1, 2016
• Last Updated: July 24, 2017
• Results First Posted: May 30, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share