Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Urinary Bladder Neoplasms

Carcinoma, Transitional Cell

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Transitional Cell Carcinoma

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Interferons

Interferon-alpha

BCG Vaccine

Interferon alpha-2

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

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.

INSTILADRIN

Colin Dinney, MD

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.

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.

The participant did not know if they received a high or low dose.

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

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

A manuscript will be published on the results of the study

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.

Treatment Emergent Adverse Events (AEs) for patients receiving study drug were described by NCI-CTCAE V4.03 terminology according to System Organ Class.

All patients were evaluated 3 Months (90 Days) after the start of treatment for recurrence of high grade disease by cytology, cystoscopy, and biopsy if clinically indicated. Patients that we free of High-Grade disease recurrence received another dose. Data are presented as the number and percent of patients with High-Grade disease recurrence.

All patients were evaluated 6 Months (180 Days) after the start of treatment for recurrence of high grade disease by cytology, cystoscopy, and biopsy if clinically indicated. Patients that we free of High-Grade disease recurrence received another dose. Data are presented as the number and percent of patients with High-Grade disease recurrence.

All patients were evaluated 9 Months (270 Days) after the start of treatment for recurrence of high grade disease by cytology, cystoscopy, and biopsy if clinically indicated. Patients that we free of High-Grade disease recurrence received a final dose. Data are presented as the number and percent of patients with High-Grade disease recurrence.

This secondary objective measures the incidence of cystectomy at 360 Days for the Efficacy Analysis Set.

Overall survival was defined as the number who survived from the first dose of rAd-IFN/Syn3 to the end of the primary assessment (360 Days) or Withdrawal.

The level of viral vector as measured by qPCR in blood was determined in all patients on the initial day of dosing Day 1 (pre-dose) and at Day 2, Day 4, Day 12, and for patients that were free of High-Grade disease recurrence and received a second dose at Day 91 (pre-dose), Day 92, Day 94, and Day 103.

The level of viral vector as measured by qPCR in urine was determined in all patients on the initial day of dosing Day 1 (pre-dose) and at Day 2, Day 4, Day 12, and for patients that were free of High-Grade disease recurrence and received a second dose at Day 91 (pre-dose), Day 92, Day 94, and Day 103.

The levels of serum IFN alpha2b protein as measured by ELISA were determined in all patients on the initial day of dosing (Pre-Dose Day 1), at Day 2, Day 4, Day 12, and for patients that were free of High-Grade disease recurrence and received subsequent doses at Day 91 (pre-dose), Day 92, Day 94, Day 103, Day 180 (pre-dose), Day 270 (pre-dose), and Day 360 or Withdrawal.

The levels of urine IFN alpha2b protein as measured by ELISA were measured in all patients on the initial day of dosing Day 1 (pre-dose) and at Day 2, Day 4, Day 12, and for patients that did not have recurrence of HGD and received a second dose at Day 91 (pre-dose), Day 92, Day 94, and Day 103.

The levels of serum anti-IFN alpha2b antibodies as measured by ELISA were determined in all patients on the initial day of dosing (Pre-Dose Day 1), at Day 12, and for patients that were free of High-Grade disease recurrence and received subsequent doses at Day 180 (pre-dose), Day 270 (pre-dose), and Day 360 or Withdrawal.

The levels of serum anti-adenovirus type 5 antibodies as measured by ELISA were determined in all patients on the initial day of dosing (Pre-Dose Day 1), at Day 12, and for patients that were free of High-Grade disease recurrence and received subsequent subsequent doses at Day 180 (pre-dose), Day 270 (pre-dose), and Day 360 or Withdrawal.

FKD Therapies Oy

Patients were randomized to the 1x10\^11 vps/ml INSTILADRIN arm.

rAd-IFN Dose 1x10^11 Vps/ml

Patients were randomized the 3x10\^11 vps/ml INSTILADRIN arm.

rAd-IFN Dose 3x10^11vps/ml

Patients were randomly assigned to the 1x10\^11vps/ml of rAd-IFN/Syn3 arm.

rAd-IFN Dose 1x10^11vps/ml

Patients were randomly assigned to the 3x10\^11vps/ml of rAd-IFN/Syn3 arm.

rAd-IFN Dose 3x10^11 Vps/ml

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

David Sawutz, PhD

The primary efficacy endpoint was the incidence of high-grade recurrence-free survival at 12 months. The proportion of patients achieving high-grade recurrence-free survival at 12 months was reported for each dose group, together with an exact 90% confidence interval for the proportion

The primary efficacy endpoint was the incidence of high-grade recurrence-free survival at 12 months. The proportion of patients achieving high-grade recurrence-free survival at 12 months was reported for each dose group, together with an exact 90% confidence interval for the proportion.

Subjects were randomly assigned to the 1x10\^11 vps/mI rAd-IFN/Syn3 arm.

Patients were randomly assigned to the 3x10\^11vps/ml rAd-IFN/Syn3 arm.

Incidence of High Grade-Recurrence Free Survival at 360 Days

Patients were randomly assigned to the 1x10\^11vps/ml rAd-IFN/Syn3 arm.

Patients were randomly assigned to the 3x10\^11 vps/ml rAd-IFN/Syn3 arm.

Safety of rAd-IFN/Syn3

Patients were randomly assigned to the 1x10\^11 vps/ml rAd-IFN/Syn3 arm.

All patients at 90 Days were assessed for High-Grade disease by cytology, cystoscopy, and biopsy if clinically indicated.

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

Patients were randomly assigned to the 1x10\^11 vps/ml rAd-IFN/Syn3 arm.

.

All patients receiving a dose at 90 Days were assessed at 180 Days for High-Grade disease by cytology, cystoscopy, and biopsy if clinically indicated.

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

All patients that received a dose at Day 180 were assessed for High-Grade disease by cytology, cystoscopy, and biopsy if clinically indicated.

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

The data are presented as the number of patients per dose group having a cystectomy during the 360 days of the study.

Incidence of Cystectomy in All Patients

Patients were randomly assigned to the 1x10\^11 vps/mI rAd-IFN/Syn3 arm.

Subjects were randomly assigned to the 3x10\^11vps/ml rAd-IFN/Syn3 arm.

The data are presented as the number of patients who survived the study (360 Days). All patients were monitored for this endpoint.

Overall Survival in All Patients.

Pre-Dose Day 1

Day 2

Day 4

Day 12

Pre-Dose Day 91

Day 92

Day 94

Day 103

Data are reported as number of patients demonstrating viral vector by qPCR in blood.

Number of Patients With Elevated Levels of Viral Vector in Blood

Data are reported as number of patients demonstrating increased levels of viral vector by qPCR in urine.

Number of Patients With Elevated Levels of Viral Vector in Urine

Day 91

Pre-Dose Day 180

Pre-Dose Day 270

Day 360 or Withdrawal

Data are reported as the number of patients with increased levels of IFN alpha2b protein in serum.

Number of Patients With Elevated IFN alpha2b Protein Levels in Serum

Data are reported as the number of patients with elevated levels of IFN alpha2b levels in urine.

Number of Patients With Elevated IFN alpha2b Protein Levels in Urine

Data are reported at Number of Patients with a Positive Titre.

Number of Patients With Elevated Levels of Anti-IFN alpha2b Antibodies in Serum

rAd-IFN Dose 3x10^11vps/mL

Data are reported at Number of Patients with a Positive Titer.

Number of Patients With Elevated Levels of Anti-Adenovirus Type 5 Antibodies in Serum.

Patients were randomized to the 1x10\^11vps/ml rAd-IFN/Syn3 arm.

A 75 mL dose of rAd-IFN/Syn3 was given as a single, one-hour intravesical administration and, depending on clinical response, was repeated every 90 Days up to a maximum of 4 instilations.

Patients were randomized to the 3x10\^11vps/ml rAd-IFN/Syn3 arm.

A 75 mL dose of rAd-IFN/Syn3 was given as a single, one-hour intravesical administration and, depending on clinical response, was repeated every 90 Days up to a maximum of 4 instilations.

Spots Global Cancer Trial Database for Intravesical Administration of rAd-IFN/Syn3 in Patients With BCG-Refractory or Relapsed Bladder Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

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