BCG-unresponsive Carcinoma in Situ of the bladder with or without Ta-T1 papillary disease MedDRA version: 20.0 Level: LLT Classification code 10007400 Term: Carcinoma in situ of the bladder System Organ Class: 100000004864
Conditions
Interventions
Product Name: ONCOFID-P-B
Product Code: ONCOFID-P-B
Pharmaceutical Form: Intravesical solution
INN or Proposed INN: ONCOFID-P20
CAS Number: 850233-83-9
Current Sponsor code: ONCOFID-P20
Other descript
Sponsors
Fidia Farmaceutici S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing and able to freely provide written informed consent (in presence of an Independent Witness if applicable) prior to performing study procedures. 2. Age 18 years or older, male or female. 3. Persistent or recurrent CIS of the bladder histologically confirmed, with or without concomitant Ta-T1 and with no evidence of metastases demonstrated by abdominal CT scan. 4. "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. 5. Complete resection of Ta-T1 papillary lesions before entering the trial in patients with concomitant CIS and papillary tumors (residual CIS acceptable). a. In patients with T1 papillary lesions undergoing resection of the base of the lesion, the biopsy should contain muscle fibers. b. In patients with high-risk disease undergoing transurethral resection of their bladder tumors, absence of locally advanced disease confirmed by pelvic examination under anesthesia. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. 7. 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. 8. Women in non-reproductive years (defined as surgically sterile or one year postmenopausal). Women of childbearing potential (WOCBP) must 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 Male patients with WOCBP partners do not need contraception measures. 9. Able and willing to comply with the scheduled visits, therapy plans, and laboratory tests required in this protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 36 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 110
Exclusion criteria
Exclusion criteria: 1. Current or previous muscle-invasive disease (T2-T4) or metastatic urothelial carcinoma. 2. Suspected hypersensitivity to paclitaxel or to any of the ONCOFID-P-B constituents. 3. 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. 4. Current or prior systemic therapy for bladder cancer. 5. 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. 6. Symptomatic urinary tract infection or bacterial cystitis. Once successfully treated (negative urine culture), patients may enter the study. 7. Major surgery, other than diagnostic, within 4 weeks prior to treatment. 8. 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. 9. 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). 10. Presence of significant urologic disease interfering with intravesical therapy. 11. Current enrollment or participation in another therapeutic clinical trial within 3 months preceding treatment start. 12. Known substance and/or alcohol abuse. 13. 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. 14. 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. 15. Subjects who have a mean QTc >480 msec at baseline and who need concomitant medications which may cause QT prolongation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the antitumor activity of ONCOFID-P-B using centrally assessed complete response rate (CRR) following 12 weekly intravesical instillations (induction phase). ;Secondary Objective: 1. To further evaluate the antitumor activity of ONCOFID-P-B using centrally assessed CRR at 6, 9, 18 and 24 months after treatment start. 2. To evaluate the duration of response (DoR). 3. To evaluate the DoR rates at 6, 9, 12, 15, 18, 21 and 24 after treatment start. 4. To evaluate progression rates at 3, 15 and 24 months after treatment start. 5. To evaluate time to progression. 6. To evaluate the rate of patients undergoing cystectomy at 3, 15 and 24 months after treatment start. 7. To evaluate event-free survival (EFS). 8. To evaluate overall survival (OS).;Primary end point(s): CRR calculated as the proportion of patients achieving a CR after 12 weekly intravesical instillations (end of induction phase). CRR will be based on central assessment of response. Local assessments will be used by Investigators to decide on whether to start the maintenance phase, while the statistical analysis of the efficacy endpoints will be performed on central assessments. A CR is defined as at least one of the following: • Negative cystoscopy and negative (including atypical) urine cytology. • Positive cystoscopy with biopsy-proven benign or low-grade NMIBC and negative cytology. • Negative cystoscopy with malignant urine cytology if cancer is found in the upper tract or prostatic urethra and random (mapping) bladder biopsies are negative. ;Timepoint(s) of evaluation of this end point: Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. CRR calculated as the proportion of patients achieving a CR at 6, 9, 18 and 24 months after treatment start 2. DoR defined as the time from first documented evidence of CR to time of documented recurrence (CIS or Ta-T1), progression to higher grade (MIBC), to extravesical disease or death 3. DoR rate calculated as the proportion of patients who maintained a CR after 6, 9, 12, 15, 18, 21 and 24 months after treatment start. 4. Progression rate calculated as the proportion of patients with muscle invasion or extravesical expansion of the disease at 3, 15 and 24 months after treatment start 5. Time to progression defined as time from treatment start to time of documented tumor progression to MIBC or extravesical disease. 6. Proportion of patients undergoing cystectomy for disease progression at 3 months (end of induction phase), 15 and 24 months after treatment start. 7. EFS defined as time from treatment start to the time of documented recurrence after CR, or progression or death due to any cause. 8. OS defined as time from treatment start to death due to any cause. ;Timepoint(s) of evaluation of this end point: Multiple, please see E.5.2 | — |
Countries
France, Italy, Spain, United States
Contacts
Public ContactNicola Giordan
Fidia Farmaceutici S.p.A.
Outcome results
None listed