paclitaxel obaluronate for Carcinoma in situ of the bladder (BCG-unresponsive)

Inclusion criteria

• {"criterion_text":"- 1. Willing and able to freely provide written informed consent (in presence of an Independent Witness if applicable) prior to performing study procedures.\n- 10. Able and willing to comply with the scheduled visits, therapy plans, and laboratory tests required in this protocol.\n- 2. Age 18 years or older, male or female.\n- 3. Persistent or recurrent CIS of the bladder histologically confirmed, with or without concomitant recurrent HG Ta-T1 and with no evidence of metastases demonstrated by abdominal CT scan or MRI.\n- 4. BCG unresponsive patients who refuse or are unfit for radical cystectomy. BCG-unresponsive disease is defined as persistent or recurrent CIS alone or with recurrent HG Ta-T1 disease within 12 months of completion of adequate BCG therapy. Adequate BCG therapy is defined as at least one of the following: 1) At least five full doses of six doses of an initial induction course plus at least two full doses of three doses of maintenance therapy. 2) At least five full doses of six doses of an initial induction course plus at least two full doses of six doses of a second induction course.\n- 5. Complete resection of Ta-T1 papillary lesions before entering the trial in patients with concomitant CIS and papillary tumors (residual CIS acceptable, obvious areas of CIS should also be fulgurated). a. In patients with T1 papillary lesions undergoing resection of the base of the lesion, the biopsy should contain muscle fibers. b. In patients undergoing transurethral resection of their bladder tumors, absence of locally advanced disease should be confirmed by pelvic examination under anesthesia.\n- 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.\n- 7. Adequate organ function: absolute neutrophil count ≥ 1,500/mm3, platelets ≥ 100,000/mm3, hemoglobin ≥ 8.5 g/dL, ALT/AST ≤ 1.5 x upper limit of normal (ULN), alkaline phosphatase ≤ 5 x ULN, total serum bilirubin ≤ 1.5 x ULN, for patients with Gilbert’s Syndrome ≤ 3 x ULN, serum creatinine ≤ 2.2 mg/dL.\n- 8. Women in non-reproductive years (defined as surgically sterile or one year postmenopausal). Women of childbearing potential (WOCBP*) must have a negative serum pregnancy test upon entry into this study and agree to use highly effective contraceptive methods, i.e. methods that can achieve a failure rate of less than 1% per year when used consistently and correctly. Such methods include: • combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: − oral − intravaginal − transdermal • progestogen-only hormonal contraception associated with inhibition of ovulation: − oral − injectable − implantable • intrauterine device (IUD) • intrauterine hormone-releasing system ( IUS) • bilateral tubal occlusion • vasectomised partner (**) • sexual abstinence (***) (*) Women of childbearing potential (WOCBP): fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy (HRT). However, in the absence of 12 months of amenorrhea, confirmation with more than one FSH measurement is required. (**) Vasectomised partner is a highly effective birth control method provided that partner is the sole sexual partner of the WOCBP trial participant and that the vasectomised partner has received medical assessment of the surgical success. (***) Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated to the study treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.\n- 9. Male patients with WOCBP partners must agree to use effective contraceptive methods, i.e.: • condom • consider contraception for non-pregnant WOCBP partner."}

Exclusion criteria

• {"criterion_text":"- 1. Current or previous muscle-invasive disease (T2-T4) or metastatic urothelial carcinoma.\n- 2. Patient with more than 12 months between inclusion (week 1) and the last BCG instillation.\n- 3. Suspected hypersensitivity to paclitaxel or to any of the ONCOFID-P-B constituents.\n- 4. Previous or concomitant urothelial carcinoma 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.\n- 5. Current or prior systemic therapy for bladder cancer.\n- 6. 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.\n- 7. Symptomatic urinary tract infection or bacterial cystitis.\n- 8. Major surgery, other than diagnostic, within 4 weeks prior to treatment.\n- 9. Patients who have previous or concurrent malignancies that require treatment and are not clinically stable; examples of permitted concurrent recent second malignancies are: adequately treated basal cell, squamous cell skin cancer, in situ carcinoma of the cervix or prostate cancer on active surveillance at low risk for progression, defined as prostate-specific antigen (PSA) <10 ng/mL, Gleason score 6 or less and cT1.\n- 18. Applies to France only: Persons deprived of liberty by judicial or administrative decisions, adults subject to a legal protection measure (under guardianship/curators), persons under protective measures and persons not affiliated with social security will be excluded from the study.\n- 10. 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).\n- 11. Presence of significant urologic disease interfering with intravesical therapy.\n- 12. Current enrollment or participation in another therapeutic clinical trial within 6 months preceding screening. Patients previously included in a BCG-only study arm might be enrolled following discussion with the medical monitor and/or sponsor if the definition of adequate BCG therapy is met.\n- 13. Known substance and/or alcohol abuse.\n- 14. 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.\n- 15. Pregnancy, lactating women or women of childbearing potential (WOCBP) unwilling to use adequate birth control measures for the duration of the study and until 6 months after the end of treatment.\n- 16. Male patients with WOCBP partners unwilling to use contraceptive methods for the duration of the study and until 6 months after the end of treatment.\n- 17. Subjects who have a mean QTc >450 msec for males and >470 msec for females at baseline and who need concomitant medications which may cause QT prolongation."}

Primary endpoints

• {"endpoint_text":"- CRR at any time within 24 months after induction or re-induction start calculated as the proportion of patients achieving a CR at any time within 24 months after induction or re-induction start. For analysis purpose, CRR will be based on central assessment of response.","definition_or_measurement_approach":"CRR calculated as the proportion of patients achieving a complete response (CR) at any time within 24 months after induction or re-induction start; for analysis CRR is based on central assessment of response."}

Secondary endpoints

• {"endpoint_text":"- 1. CRR calculated as the proportion of patients achieving a CR at EOIT/EORIT, 6, 9, 12, 15, 18, 21, 24, 30, 36, 42 and 48 months after induction or re-induction start.","definition_or_measurement_approach":"CRR at specified timepoints calculated as proportion of patients achieving CR at each listed timepoint (EOIT/EORIT and specified months)."}
• {"endpoint_text":"- 2. DoR defined as the time from first documented evidence of CR to time of documented recurrence (CIS or HG Ta-T1), progression to MIBC, to extravesical disease or death.","definition_or_measurement_approach":"DoR = time from first documented CR to documented recurrence (CIS or HG Ta-T1), progression to muscle-invasive bladder cancer (MIBC), extravesical disease or death."}
• {"endpoint_text":"- 3. DoR rate calculated as the proportion of patients who maintained a CR after 6, 9, 12, 15, 18, 21, 24, 30, 36, 42 and 48 months after induction or re-induction start.","definition_or_measurement_approach":"Proportion of patients with maintained CR at each specified timepoint."}
• {"endpoint_text":"- 4. Progression rate calculated as the proportion of patients with tumor progression to MIBC or extravesical disease at EOIT/EORIT, 15, 24 and 48 months after induction or re-induction start.","definition_or_measurement_approach":"Proportion of patients with tumor progression to MIBC or extravesical disease at specified timepoints."}
• {"endpoint_text":"- 5. Time to progression defined as time from induction start to time of documented tumor progression to MIBC or extravesical disease.","definition_or_measurement_approach":"Time-to-event endpoint measured from induction start to documented progression to MIBC or extravesical disease."}
• {"endpoint_text":"- 6. Proportion of patients undergoing cystectomy for disease progression at EOIT/EORIT, 9, 15, 24 and 48 months after induction or re-induction start.","definition_or_measurement_approach":"Proportion undergoing cystectomy for progression at specified timepoints."}
• {"endpoint_text":"- 7. Time to cystectomy defined as time from start of treatment to the date of cystectomy.","definition_or_measurement_approach":"Time from treatment start to cystectomy date."}
• {"endpoint_text":"- 8. EFS defined as time from treatment start to the time of documented recurrence after CR, or progression or death due to any cause.","definition_or_measurement_approach":"Event-free survival measured from treatment start to documented recurrence after CR, progression, or death."}
• {"endpoint_text":"- 9. OS defined as time from treatment start to death due to any cause.","definition_or_measurement_approach":"Overall survival measured from treatment start to death from any cause."}

Methods

• Pre-screening using Trialbee (documented duty: Pre-screening) to identify potential participants.
• Digital advertising and social media campaigns (documents: Social media kit; Digital Ads Copy_SocialMedia; Social Media Kit) targeting potential patients.
• Study website content and website privacy policies (documents: Website content; Study Website Privacy Policy) for participant information and online pre-screening.
• Prescreener questionnaire and privacy policy for pre-screening (documents: Preselection questionnaire; Prescreener Questionnaire; Privacy Policy Prescreener).
• Participant-facing printed materials and flyers (documents: Participant Flyer; Brochure).
• Video scripts for patient-facing videos explaining consent and trial participation (documents: Script Video_consentement; Script Video_essai clinique; Script Video_Guide participation).
• Healthcare professional outreach (Dear Colleague letters, HCP Factsheet) to refer patients from clinics.
• RTSM/central randomisation and trial systems support via Medidata (rtsmsupport@mdsol.com) for electronic screening/management.

France

Earliest CTIS Part Ii Submission Date

03-04-2024

Latest Decision Or Authorization Date

02-04-2026

Processing Time Days

729

Number Of Sites

5

Number Of Participants

35

Italy

Earliest CTIS Part Ii Submission Date

03-04-2024

Latest Decision Or Authorization Date

24-03-2026

Processing Time Days

720

Number Of Sites

12

Number Of Participants

53

Spain

Earliest CTIS Part Ii Submission Date

03-04-2024

Latest Decision Or Authorization Date

25-03-2026

Processing Time Days

721

Number Of Sites

11

Number Of Participants

35

Poland

Earliest CTIS Part Ii Submission Date

03-04-2024

Latest Decision Or Authorization Date

27-03-2026

Processing Time Days

723

Number Of Sites

1

Number Of Participants

5

Primary sponsor

Full Name

Fidia Farmaceutici S.p.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Italy

Contract research organisations

Name

Medpace Finland Oy

Responsibilities

sponsorDuties codes: [1,10,11,12,13,2,3,5,6] (as listed in third-party record)

Third parties

• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: [7]; contact: rtsmsupport@mdsol.com","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Sweden","full_name":"Trialbee AB","duties_or_roles":"Pre-screening","organisation_type":"Pharmaceutical company"}
• {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"sponsorDuties codes: [1,10,11,12,13,2,3,5,6] (multiple operational/study support roles as listed)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Molecular Pathology Laboratory Network Inc.","duties_or_roles":"sponsorDuties codes: [4]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"sponsorDuties codes: [14]","organisation_type":"Pharmaceutical company"}