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Phase III, Single-arm Study to Evaluate the Efficacy and Safety of ONCOFID-P-B (Paclitaxel-hyaluronic Acid Conjugate) Administered Intravesically to Patients With BCG-unresponsive Carcinoma in Situ of the Bladder With or Without Ta-T1 Papillary Disease

INTRODUCTION

  • Org Study ID: R39_21_01
  • Secondary ID: N/A
  • NTC ID: NCT05024773
  • Sponsor: Fidia Farmaceutici s.p.a.

BRIEF SUMMARY

This is a phase III, single-arm, multicenter, international study to assess the efficacy and safety of ONCOFID-P-B following intravesical instillation in adult patients with histologically and cytologically confirmed CIS, with or without concomitant Ta-T1, who are unresponsive to BCG therapy and unwilling or unfit to undergo radical cystectomy.

After providing written informed consent (in presence of an Independent Witness, if applicable), patients will receive an induction therapy consisting of 12 weekly intravesical instillations of ONCOFID-P-B (induction phase). Patients who achieve a CR by Investigator assessment at the end of the induction phase will enter the maintenance phase and receive monthly treatment for an additional 12 months or until recurrence of CIS/Ta-T1 or progression to MIBC or extravesical disease.

  • Overall Status
    Recruiting
  • Start Date
    December 29, 2022
  • Phase
    Phase 3
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Centrally assessed Complete Response Rate (CRR) - end of induction phase

Primary Outcome 1 - Timeframe: CRR will be evaluated at the end of the induction phase, at 12 weeks

CONDITION

  • Bladder Carcinoma in Situ (CIS)

ELIGIBILITY

Inclusion Criteria:
Willing and able to freely provide written informed consent (in presence of an Independent Witness if applicable) prior to performing study procedures.

- Age 18 years or older, male or female.

- Persistent or recurrent histologically confirmed CIS of the bladder with or without concomitant Ta-T1 and with no evidence of metastases demonstrated by abdominal CT scan.
"BCG unresponsive" patients who refuse radical cystectomy or are not clinically suitable for cystectomy. BCG unresponsive disease includes BCG refractory (persistent high-grade disease at 6 months despite adequate BCG treatment) and BCG relapsing (recurrence of high-grade disease after achieving a disease-free state at 6 months after adequate BCG). Patients can be within 6 to 9 months of the last BCG exposure, thereby allowing a 3-month lead time for referral.
Adequate BCG therapy is defined as at least one of the following:
At least five of six doses of an initial induction course plus at least two of three doses of maintenance therapy.

- At least five of six doses of an initial induction course plus at least two of six doses of a second induction course.

- Complete resection of Ta-T1 papillary lesions before entering the trial in patients with concomitant CIS and papillary tumors (residual CIS acceptable).

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

- Adequate organ function: absolute neutrophil count ≥ 1,500/mm3, platelets ≥ 100,000/mm3, hemoglobin ≥ 10.0 g/dL, ALT/AST ≤ 5 x upper limit of normal (ULN), alkaline phosphatase ≤ 5 x ULN, total serum bilirubin ≤ 1.5 x ULN, serum creatinine ≤ 2.2 mg/dL.
Female in non-reproductive years (defined as surgically sterile or one year postmenopausal). Female of childbearing potential must agree to practice complete abstinence or agree to use highly effective contraceptive methods, which include:
Male sterilization (at least 6 months prior to screening). The vasectomized male partner should be the sole partner for that subject.

- Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system, or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception.
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.
Able and willing to comply with the scheduled visits, therapy plans, and laboratory tests required in this protocol.
Exclusion Criteria:
Current or previous muscle-invasive disease (T2-T4) or metastatic urothelial carcinoma.

- Suspected hypersensitivity to paclitaxel or to any of the Oncofid-P-B constituents.

- Previous or concomitant cancer of the upper urinary tract or the prostatic urethra. Freedom from upper tract disease must be demonstrated by intravenous pyelogram, retrograde pyelogram, CT scan or MRI.

- Current or prior systemic therapy for bladder cancer.

- Intravesical therapy within 4 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 between 14 to 60 days prior to beginning study treatment, or previous intravesical BCG therapy, which can be given at least 5 weeks before the diagnostic biopsy required for study entry.

- Symptomatic urinary tract infection or bacterial cystitis. Once successfully treated (negative urine culture), patients may enter the study.

- Major surgery, other than diagnostic, within 4 weeks prior to treatment.

- Previous (within the last 5 years) or current malignancies at other sites, except for adequately treated basal cell or squamous cell skin cancer or in situ carcinoma of the cervix uteri.

- Subjects who, in the opinion of the Investigator, cannot tolerate intravesical administration or intravesical surgical manipulation (cystoscopy, biopsy) due to the presence of serious comorbid condition(s) (e.g., uncontrolled cardiac or respiratory disorders).

- Presence of significant urologic disease interfering with intravesical therapy.

- Current enrollment or participation in another therapeutic clinical trial within 3 months preceding treatment start.

- Known substance and/or alcohol abuse.

- Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry in this study or could compromise protocol objectives.

- Pregnancy, lactating women or women of childbearing potential unwilling to use adequate birth control measures for the duration of the study and until 3 months after the end of treatment.

- Subjects who have a mean QTc >480 msec at baseline and who need concomitant medications which may cause QT prolongation.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: N/A

Role: N/A

Affiliation: N/A

Overall Contact

Name: N/A

Phone: +390498232512

Email: ngiordan@fidiapharma.it

LOCATION

Facility Status Contact
Facility: Ochsner Clinic Foundation
New Orleans, Louisiana 70121
United States
Status: Recruiting Contact: Contact
Arcot