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

Superficial Bladder Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01687244
• Other study ID #: rAd-IFN-CS-002
• Status: Completed
• Phase: Phase 2
• First received: September 6, 2012
• Last updated: February 2, 2016
• Start date: September 2012
• Est. completion date: January 2016

Study information

• Verified date: March 2015
• Source: FKD Therapies Oy
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: January 2016
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Superficial Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
FKD Therapies Oy

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To evaluate the incidence of high grade-recurrence-free survival at 3, 6 and 9 months.		3, 6, and 9 months	No
Primary	To evaluate the incidence of high grade-recurrence free survival following up to 4 instillations of INSTILADRIN		12 months	No
Secondary	Evaluate the safety of rAd-IFN/Syn3 instillation as assessed by NCI-CTCAE V4.03		12 Months	Yes