Clinical Trials /

A Study to Evaluate INSTILADRIN® in Patients With High-Grade, Bacillus Calmette-Guerin (BCG) Unresponsive NMIBC

NCT02773849

Description:

Previous multi-dose Phase I and Phase II clinical studies have demonstrated that INSTILADRIN (nadofaragene firadenovec) is a safe and effective treatment for BCG-refractory and recurrent NMIBC. This Phase III study is designed to expand those observations using a high dose of INSTILADRIN in patients that are "BCG Unresponsive" which refers to patients with high-grade NMIBC who are unlikely to benefit from and should not receive further intravesical BCG.

Related Conditions:
  • Bladder Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate INSTILADRIN® in Patients With High Grade, Bacillus Calmette-Guerin (BCG) Unresponsive NMIBC
  • Official Title: A Phase III, Open Label Study to Evaluate the Safety and Efficacy of INSTILADRIN® (rAd-IFN)/Syn3) Administered Intravesically to Patients With High Grade, BCG Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC)

Clinical Trial IDs

  • ORG STUDY ID: rAd-IFN-CS-003
  • NCT ID: NCT02773849

Conditions

  • Superficial Bladder Cancer

Interventions

DrugSynonymsArms
INSTILADRINnadofaragene firadenavecINSTILADRIN nadofaragene firodenavec

Purpose

Previous multi-dose Phase I and Phase II clinical studies have demonstrated that Instiladrin nadofaragene firadenovec is a safe and effective treatment for BCG-refractory and recurrent NMIBC. This Phase III study is designed to expand those observations using a high dose of Instiladrin in patients that are "BCG Unresponsive" which refers to patients with high grade NMIBC who are unlikely to benefit from and should not receive further intravesical BCG.

Detailed Description

      Recombinant IFN alpha2b has pleiotropic effects that contribute to antitumor activity in
      Non-Muscle Invasive Bladder Cancer (NMIBC). Instiladrin nadofaragene firadenovec is a
      non-replicating adenovirus vector harboring the human IFN alpha2b gene. When combined with
      the excipient Syn3, intravesical administration of the rAd-IFN results in transduction of the
      virus into the epithelial cell lining in the bladder. The IFN alpha2b gene is incorporated
      into the cellular DNA resulting in the synthesis and expression of large amount of IFN
      alpha2b protein. Clinical studies have confirmed that IFN alpha2b protein can be measured in
      patients treated with Instiladrin within 24 hours after dosing.
    

Trial Arms

NameTypeDescriptionInterventions
INSTILADRIN nadofaragene firodenavecExperimentalIntravesical administration of INSTILADRIN nadofaragene firadenovec into the bladder

    Eligibility Criteria

            Inclusion Criteria:
    
              1. Aged 18 years or older at the time of consent
    
              2. Able to give informed consent
    
              3. Have, at entry, confirmed by a pathology report:
    
                 Carcinoma in Situ (CIS) only; Ta/T1 high grade disease with concomitant CIS or Ta/T1
                 high grade disease without concomitant CIS
    
              4. Are "BCG Unresponsive" which refers to patients with high grade NMIBC who are unlikely
                 to benefit from and who will not receive further intravesical BCG. The term "BCG
                 unresponsive" includes patients who did not respond to BCG treatment and have a
                 persistent high grade recurrence within 12 months after BCG was initiated, and those
                 who despite an initial complete response (CR) to BCG, relapse with high grade NMIBC
                 within 12 months of their last intravesical treatment with BCG. The following criteria
                 define the patients who may be included in the study:
    
                   -  Have received at least 2 previous courses of BCG within a 12 month period -
                      defined as at least 5 of 6 induction BCG instillations and at least 2 out of 3
                      instillations of maintenance BCG, or at least two of six instillations of a
                      second induction course, where maintenance BCG is not given
    
                        -  Exception: those who have T1 high grade disease at first evaluation after
                           induction BCG alone (at least 5 of 6 doses) may qualify in the absence of
                           disease progression
    
                   -  At the time of tumor recurrence, patients with CIS alone or high grade Ta/T1 with
                      CIS should be within 12 months of last exposure to BCG and patients with Ta/T1
                      without CIS should be within 6 months of last exposure to BCG
    
                   -  No maximum limit to the amount of BCG administered
    
                   -  All visible papillary tumors must be resected and those with persistent T1
                      disease on transurethral resection of bladder tumor (TURBT) should undergo an
                      additional re-TURBT within 14 to 60 days prior to beginning study treatment.
                      Obvious areas of CIS should also be fulgurated.
    
              5. Available for the whole duration of the study
    
              6. Life expectancy >2 years, in the opinion of the investigator
    
              7. Eastern Cooperative Oncology Group (ECOG) status 2 or less
    
              8. Absence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within
                 the prostatic urethra. Freedom from upper tract disease (if clinically indicated) as
                 indicated by no evidence of upper tract tumor by either intravenous pyelogram,
                 retrograde pyelogram, computed tomography (CT) scan with or without urogram, or MRI
                 with or without urogram performed within 6 months of enrollment
    
              9. Patients with prostate cancer on active surveillance at low risk for progression,
                 defined as Prostate-Specific Antigen (PSA) < 10 ng/dL, Gleason score 6 and clinical
                 stage tumor-1 (cT1) are permitted to be in the study at the discretion of the
                 investigator (see exclusion criteria 10).
    
             10. Female patients 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 patients must be
                 postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile.
                 'Maximally effective birth control' means that the patient, if sexually active, should
                 be using a combination of two methods of birth control that are approved and
                 recognized to be effective by Regulatory Agencies
    
             11. Male patients 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
    
             12. Adequate lab values
    
            Exclusion Criteria:
    
              1. Current or previous evidence of muscle invasive (muscularis propria) or metastatic
                 disease present at the time of screening. Examples that increase the risk of
                 metastatic disease are (but not limited to):
    
                   -  Presence of lymphovascular invasion and/micropapillary disease as shown in the
                      histology of the biopsy sample
    
                   -  Patients with T1 disease accompanied by the presence of hydronephrosis
    
              2. Current systemic therapy for bladder cancer
    
              3. Current or prior pelvic external beam radiotherapy within 5 years of entry
    
              4. Prior treatment with adenovirus-based drugs
    
              5. Suspected hypersensitivity to IFN alfa2b
    
              6. Symptomatic urinary tract infection or bacterial cystitis (once satisfactorily
                 treated, patients can enter the study)
    
              7. Clinically significant and unexplained elevated liver or renal function tests
    
              8. Women who are pregnant or lactating or refuse to commit to use contraception anytime
                 during the study
    
              9. Any other significant disease or clinical findings which in the opinion of the
                 investigator would prevent study entry
    
             10. History of malignancy of other organ system within past 5 years, except treated basal
                 cell carcinoma or squamous cell carcinoma of the skin and ≤ pathological tumor-2 (pT2)
                 upper tract urothelial carcinoma at least 24 months after nephroureterectomy. Also
                 patients with genitourinary cancers other than urothelial cancer or prostate cancer
                 that are under active surveillance are excluded (see inclusion criterion 9)
    
             11. Patients who cannot hold instillation for 1 hour
    
             12. Patients who cannot tolerate intravesical dosing or intravesical surgical manipulation
    
             13. Intravesical therapy within 8 weeks prior to beginning study treatment with the
                 exception of:
    
                   -  cytotoxic agents (e.g. Mitomycin C, doxorubicin and epirubicin) when administered
                      as a single instillation immediately following a TURBT procedure which is
                      permitted up to 14 to 60 days prior to beginning study treatment
    
                   -  previous intravesical BCG therapy, which can be given at least 5 weeks before the
                      diagnostic biopsy required for entry into the study
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:To evaluate the incidence of Event-Free Survival at 12 months, where Event-Free Survival is defined as High-Grade-Recurrence Free Survival
    Time Frame:12 Months
    Safety Issue:
    Description:Incidence of Event-Free Survival will be measured by determining the number of patients without recurrence of high grade disease using results from urine cytology, cystoscopy, and biopsy of the bladder if clinically indicated.

    Secondary Outcome Measures

    Measure:To determine the incidence of Event Free Survival during the first 12 months of the Long Term Follow Up period, where Event-Free Survival is defined as High-Grade-Recurrence Free Survival
    Time Frame:Up to 24 months
    Safety Issue:
    Description:Incidence of Event-Free survival will be measured by determining the number of patients without recurrence of high grade disease using results from urine cytology, cystoscopy, and biopsy of the bladder if clinically indicated.
    Measure:The evaluate incidence of Event-Free Survival at 3, 6 and 9 months where Event Free Survival is defined as High-Grade-Recurrence-Free Survival
    Time Frame:up to 9 months
    Safety Issue:
    Description:Incidence of Event-Free survival will be measured by determining the number of patients without recurrence of high grade disease using results from urine cytology, cystoscopy, and biopsy of the bladder if clinically indicated.
    Measure:To determine time to recurrence of High Grade Disease
    Time Frame:12 months
    Safety Issue:
    Description:
    Measure:To determine the incidence of cystectomy in the study
    Time Frame:12 Months
    Safety Issue:
    Description:The incidence of and time to csytectomy will be measured in the study
    Measure:To determine the overall survival in all patients
    Time Frame:12 Months
    Safety Issue:
    Description:
    Measure:To determine the anti-adenoviral antibody levels for correlation to response rate
    Time Frame:12 Months
    Safety Issue:
    Description:
    Measure:To evaluate the safety of INSTILADRIN
    Time Frame:24 Months
    Safety Issue:
    Description:The type, incidence, relatedness and severity of treatment emergent adverse events of INSTILADRIN as assessed by NCI-CTCAE V4.03 will be monitored.

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:FKD Therapies Oy

    Trial Keywords

    • IFN
    • BCG-unresponsive
    • Non-Muscle Invasive Bladder Cancer

    Last Updated

    February 5, 2018