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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
FKD Therapies Oy
ClinicalTrials.gov Identifier:
NCT01687244
First received: September 6, 2012
Last updated: March 5, 2015
Last verified: March 2015
  Purpose

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.


Condition Intervention Phase
Superficial Bladder Cancer
Drug: INSTILADRIN
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Open Label, Parallel Arm Study to Evaluate the Safety and Efficacy of rAd-IFN/Syn3 Following Intravesical Administration in Subjects With High Grade, BCG Refractory or Relapsed Superficial Bladder Cancer

Resource links provided by NLM:


Further study details as provided by FKD Therapies Oy:

Primary Outcome Measures:
  • To evaluate the incidence of high grade-recurrence free survival following up to 4 instillations of INSTILADRIN [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Evaluate the safety of rAd-IFN/Syn3 instillation as assessed by NCI-CTCAE V4.03 [ Time Frame: 12 Months ] [ Designated as safety issue: Yes ]

Other Outcome Measures:
  • To evaluate the incidence of high grade-recurrence-free survival at 3, 6 and 9 months. [ Time Frame: 3, 6, and 9 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: September 2012
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rAd-IFN Dose 1x10^11vps/ml
Subjects will be randomly assigned to one of two INSTILADRIN arms.
Drug: INSTILADRIN
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.
Other Name: rAd-IFN/Syn3
Experimental: rAd-IFN dose 3x10^11 vps/ml
Subjects will be randomly assigned to one of two INSTILADRIN arms.
Drug: INSTILADRIN
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.
Other Name: rAd-IFN/Syn3

Detailed Description:

Criteria for Evaluation:

Efficacy: A Response is defined as no evidence of recurrence of a high grade tumor by cystoscopy, cytology or if clinically indicated, biopsy.

Safety: The safety and tolerability of INSTILADRIN will be evaluated based on adverse event reports, vital signs, ECGs, clinical laboratory values and results of physical examination.

  Eligibility

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

Inclusion Criteria:

  1. Aged 18 years or older at the time of consent
  2. Able to give informed consent
  3. 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

  4. Complete resection of visible papillary lesions or CIS by TURBT or endoscopic resection between 14 and 60 days prior to beginning study treatment
  5. Available for the whole duration of the study
  6. Life expectancy >2 years, in the opinion of the investigator
  7. ECOG status 2 or less
  8. Absence of upper tract urothelial carcinoma
  9. 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.
  10. 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.
  11. Adequate laboratory values.

    • Hemoglobin ≥10 g/dL.
    • WBC ≥4000/μL.
    • ANC ≥2000/μL.
    • Platelet count ≥100,000/μL.
    • INR within institutional normal limits.
    • aPTT within institutional normal limits.
    • AST ≤1.5 x ULN.
    • ALT ≤1.5 x ULN.
    • Total bilirubin within institutional normal limits.
    • Creatinine ≤1.5 x ULN.

Exclusion Criteria:

  1. Current or previous evidence of muscle invasive or metastatic disease
  2. Current systemic therapy for bladder cancer
  3. Current or prior pelvic external beam radiotherapy
  4. Prior treatment with adenovirus-based drugs
  5. Suspected hypersensitivity to interferon alpha
  6. Existing urinary tract infection or bacterial cystitis
  7. Clinically significant and unexplained elevated liver or renal function tests
  8. Women who are pregnant or lactating
  9. Severe cardiovascular disease
  10. History of malignancy of other organ system within past 5 years (except treated basal cell carcinoma or squamous cell carcinoma of the skin)
  11. Subjects who cannot hold instillation for 1 hour
  12. Subjects who cannot tolerate intravesical dosing or intravesical surgical manipulation
  13. Intravesical therapy within 6 weeks of enrollment
  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: NCT01687244

Sponsors and Collaborators
FKD Therapies Oy
Investigators
Study Chair: Colin Dinney, MD M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: FKD Therapies Oy
ClinicalTrials.gov Identifier: NCT01687244     History of Changes
Other Study ID Numbers: rAd-IFN-CS-002
Study First Received: September 6, 2012
Last Updated: March 5, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by FKD Therapies Oy:
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

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms

ClinicalTrials.gov processed this record on July 30, 2015