Superficial Bladder Cancer
Conditions
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
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.
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.
Interventions
DRUGINSTILADRIN
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.
Sponsors
FKD Therapies Oy
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
The participant did not know if they received a high or low dose.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of High Grade-Recurrence Free Survival at 360 Days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of rAd-IFN/Syn3 | 360 Days | Treatment Emergent Adverse Events (AEs) for patients receiving study drug were described by NCI-CTCAE V4.03 terminology according to System Organ Class. |
| Incidence of High Grade-Recurrence-Free Survival at 6 Months (180 Days). | 180 Days | 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. |
| Incidence of High Grade-Recurrence-Free Survival at 9 Months (270 Days). | 270 Days | 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. |
| Incidence of Cystectomy in All Patients | 360 Days | This secondary objective measures the incidence of cystectomy at 360 Days for the Efficacy Analysis Set. |
| Overall Survival in All Patients. | 360 Days | 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. |
| Incidence of High Grade Recurrence-Free Survival at 3 Months (90 Days). | 90 Days | 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. |
| Number of Patients With Elevated Levels of Viral Vector in Urine | 103 Days | 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. |
| Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | 360 Days | 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. |
| Number of Patients With Elevated IFN alpha2b Protein Levels in Urine | 103 Days | 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. |
| Number of Patients With Elevated Levels of Anti-IFN alpha2b Antibodies in Serum | 360 Days | 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. |
| Number of Patients With Elevated Levels of Anti-Adenovirus Type 5 Antibodies in Serum. | 360 Days | 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. |
| Number of Patients With Elevated Levels of Viral Vector in Blood | 103 Days | 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| rAd-IFN Dose 1x10^11vps/ml Patients were randomly assigned to the 1x10\^11vps/ml of rAd-IFN/Syn3 arm. | 21 |
| rAd-IFN Dose 3x10^11 Vps/ml Patients were randomly assigned to the 3x10\^11vps/ml of rAd-IFN/Syn3 arm. | 19 |
| Total | 40 |
Baseline characteristics
| Characteristic | rAd-IFN Dose 3x10^11 Vps/ml | rAd-IFN Dose 1x10^11vps/ml | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 12 Participants | 19 Participants | 31 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 2 Participants | 9 Participants |
| Age, Continuous | 71.1 years STANDARD_DEVIATION 9.42 | 71.6 years STANDARD_DEVIATION 8.07 | 71.1 years STANDARD_DEVIATION 9.42 |
| Region of Enrollment United States | 19 Participants | 21 Participants | 40 Participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 7 Participants |
| Sex: Female, Male Male | 14 Participants | 19 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 21 | 19 / 19 |
| serious Total, serious adverse events | 3 / 21 | 2 / 19 |
Outcome results
Primary
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.
Time frame: 360 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rAd-IFN Dose 1x10^11 Vps/ml | Incidence of High Grade-Recurrence Free Survival at 360 Days | 7 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Incidence of High Grade-Recurrence Free Survival at 360 Days | 7 Participants |
Comparison: 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 proportion90% CI: [16.8, 53.6]
Comparison: 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.90% CI: [18.8, 58.2]
Secondary
Incidence of Cystectomy in All Patients
This secondary objective measures the incidence of cystectomy at 360 Days for the Efficacy Analysis Set.
Time frame: 360 Days
Population: The data are presented as the number of patients per dose group having a cystectomy during the 360 days of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rAd-IFN Dose 1x10^11 Vps/ml | Incidence of Cystectomy in All Patients | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Incidence of Cystectomy in All Patients | 0 Participants |
Secondary
Incidence of High Grade Recurrence-Free Survival at 3 Months (90 Days).
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.
Time frame: 90 Days
Population: All patients at 90 Days were assessed for High-Grade disease by cytology, cystoscopy, and biopsy if clinically indicated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rAd-IFN Dose 1x10^11 Vps/ml | Incidence of High Grade Recurrence-Free Survival at 3 Months (90 Days). | 10 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Incidence of High Grade Recurrence-Free Survival at 3 Months (90 Days). | 13 Participants |
Secondary
Incidence of High Grade-Recurrence-Free Survival at 6 Months (180 Days).
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.
Time frame: 180 Days
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rAd-IFN Dose 1x10^11 Vps/ml | Incidence of High Grade-Recurrence-Free Survival at 6 Months (180 Days). | 8 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Incidence of High Grade-Recurrence-Free Survival at 6 Months (180 Days). | 9 Participants |
Secondary
Incidence of High Grade-Recurrence-Free Survival at 9 Months (270 Days).
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.
Time frame: 270 Days
Population: All patients that received a dose at Day 180 were assessed for High-Grade disease by cytology, cystoscopy, and biopsy if clinically indicated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rAd-IFN Dose 1x10^11 Vps/ml | Incidence of High Grade-Recurrence-Free Survival at 9 Months (270 Days). | 8 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Incidence of High Grade-Recurrence-Free Survival at 9 Months (270 Days). | 9 Participants |
Secondary
Number of Patients With Elevated IFN alpha2b Protein Levels in Serum
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.
Time frame: 360 Days
Population: Data are reported as the number of patients with increased levels of IFN alpha2b protein in serum.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Day 12 | 1 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Day 94 | 1 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Day 4 | 1 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Day 103 | 1 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Day 91 | 1 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Pre-Dose Day 180 | 0 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Day 2 | 2 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Pre-Dose Day 270 | 0 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Day 92 | 1 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Day 360 or Withdrawal | 0 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Pre-Dose Day 1 | 1 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Day 360 or Withdrawal | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Pre-Dose Day 1 | 1 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Day 2 | 10 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Day 4 | 6 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Day 12 | 1 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Day 91 | 1 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Day 92 | 1 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Day 94 | 1 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Day 103 | 1 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Pre-Dose Day 180 | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Serum | Pre-Dose Day 270 | 0 Participants |
Secondary
Number of Patients With Elevated IFN alpha2b Protein Levels in Urine
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.
Time frame: 103 Days
Population: Data are reported as the number of patients with elevated levels of IFN alpha2b levels in urine.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Urine | Pre-Dose Day 1 | 0 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Urine | Day 2 | 21 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Urine | Day 4 | 17 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Urine | Day 12 | 1 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Urine | Pre-Dose Day 91 | 0 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Urine | Day 92 | 8 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Urine | Day 94 | 5 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Urine | Day 103 | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Urine | Day 103 | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Urine | Pre-Dose Day 1 | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Urine | Pre-Dose Day 91 | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Urine | Day 2 | 18 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Urine | Day 94 | 3 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Urine | Day 4 | 18 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Urine | Day 92 | 9 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated IFN alpha2b Protein Levels in Urine | Day 12 | 6 Participants |
Secondary
Number of Patients With Elevated Levels of Anti-Adenovirus Type 5 Antibodies in Serum.
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.
Time frame: 360 Days
Population: Data are reported at Number of Patients with a Positive Titer.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Anti-Adenovirus Type 5 Antibodies in Serum. | Day 12 | 2 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Anti-Adenovirus Type 5 Antibodies in Serum. | Pre-Dose Day 270 | 6 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Anti-Adenovirus Type 5 Antibodies in Serum. | Pre-Dose Day 180 | 6 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Anti-Adenovirus Type 5 Antibodies in Serum. | Day 360 or Withdrawal | 12 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Anti-Adenovirus Type 5 Antibodies in Serum. | Pre-Dose Day 1 | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Anti-Adenovirus Type 5 Antibodies in Serum. | Day 360 or Withdrawal | 7 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Anti-Adenovirus Type 5 Antibodies in Serum. | Pre-Dose Day 1 | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Anti-Adenovirus Type 5 Antibodies in Serum. | Day 12 | 1 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Anti-Adenovirus Type 5 Antibodies in Serum. | Pre-Dose Day 180 | 6 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Anti-Adenovirus Type 5 Antibodies in Serum. | Pre-Dose Day 270 | 5 Participants |
Secondary
Number of Patients With Elevated Levels of Anti-IFN alpha2b Antibodies in Serum
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.
Time frame: 360 Days
Population: Data are reported at Number of Patients with a Positive Titre.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Anti-IFN alpha2b Antibodies in Serum | Day 12 | 0 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Anti-IFN alpha2b Antibodies in Serum | Pre-Dose Day 270 | 0 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Anti-IFN alpha2b Antibodies in Serum | Pre-Dose Day 180 | 0 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Anti-IFN alpha2b Antibodies in Serum | Day 360 or Withdrawal | 0 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Anti-IFN alpha2b Antibodies in Serum | Pre-Dose Day 1 | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Anti-IFN alpha2b Antibodies in Serum | Day 360 or Withdrawal | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Anti-IFN alpha2b Antibodies in Serum | Pre-Dose Day 1 | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Anti-IFN alpha2b Antibodies in Serum | Day 12 | 1 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Anti-IFN alpha2b Antibodies in Serum | Pre-Dose Day 180 | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Anti-IFN alpha2b Antibodies in Serum | Pre-Dose Day 270 | 0 Participants |
Secondary
Number of Patients With Elevated Levels of Viral Vector in Blood
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.
Time frame: 103 Days
Population: Data are reported as number of patients demonstrating viral vector by qPCR in blood.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Viral Vector in Blood | Pre-Dose Day 1 | 0 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Viral Vector in Blood | Day 2 | 0 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Viral Vector in Blood | Day 4 | 0 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Viral Vector in Blood | Day 12 | 0 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Viral Vector in Blood | Pre-Dose Day 91 | 0 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Viral Vector in Blood | Day 92 | 0 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Viral Vector in Blood | Day 94 | 0 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Viral Vector in Blood | Day 103 | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Viral Vector in Blood | Day 103 | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Viral Vector in Blood | Pre-Dose Day 1 | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Viral Vector in Blood | Pre-Dose Day 91 | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Viral Vector in Blood | Day 2 | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Viral Vector in Blood | Day 94 | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Viral Vector in Blood | Day 4 | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Viral Vector in Blood | Day 92 | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Viral Vector in Blood | Day 12 | 0 Participants |
Secondary
Number of Patients With Elevated Levels of Viral Vector in Urine
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.
Time frame: 103 Days
Population: Data are reported as number of patients demonstrating increased levels of viral vector by qPCR in urine.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Viral Vector in Urine | Pre-Dose Day 91 | 1 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Viral Vector in Urine | Pre-Dose Day 1 | 1 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Viral Vector in Urine | Day 92 | 10 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Viral Vector in Urine | Day 4 | 20 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Viral Vector in Urine | Day 94 | 8 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Viral Vector in Urine | Day 2 | 21 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Viral Vector in Urine | Day 103 | 2 Participants |
| rAd-IFN Dose 1x10^11 Vps/ml | Number of Patients With Elevated Levels of Viral Vector in Urine | Day 12 | 17 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Viral Vector in Urine | Day 103 | 4 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Viral Vector in Urine | Pre-Dose Day 1 | 0 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Viral Vector in Urine | Day 2 | 18 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Viral Vector in Urine | Day 4 | 19 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Viral Vector in Urine | Pre-Dose Day 91 | 2 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Viral Vector in Urine | Day 92 | 11 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Viral Vector in Urine | Day 94 | 11 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Number of Patients With Elevated Levels of Viral Vector in Urine | Day 12 | 16 Participants |
Secondary
Overall Survival in All Patients.
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.
Time frame: 360 Days
Population: The data are presented as the number of patients who survived the study (360 Days). All patients were monitored for this endpoint.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rAd-IFN Dose 1x10^11 Vps/ml | Overall Survival in All Patients. | 21 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Overall Survival in All Patients. | 19 Participants |
Secondary
Safety of rAd-IFN/Syn3
Treatment Emergent Adverse Events (AEs) for patients receiving study drug were described by NCI-CTCAE V4.03 terminology according to System Organ Class.
Time frame: 360 Days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| rAd-IFN Dose 1x10^11 Vps/ml | Safety of rAd-IFN/Syn3 | 20 Participants |
| rAd-IFN Dose 3x10^11vps/ml | Safety of rAd-IFN/Syn3 | 19 Participants |